Wiedemann-Steiner Syndrome

Mendelian MONDO:0011518 Intellectual disability syndrome Mendelian neurodevelopmental disorder

Wiedemann-Steiner Syndrome (WDSTS; OMIM 605130) is a rare autosomal dominant chromatinopathy caused by heterozygous pathogenic variants in KMT2A, encoding a histone H3 lysine 4 (H3K4) methyltransferase. The condition is characterised by global developmental delay, intellectual disability (typically mild to moderate), short stature, hypertrichosis (especially elbow hypertrichosis), characteristic craniofacial dysmorphism, and multi-system concomitants including gastrointestinal, skeletal, cardiac, and genitourinary anomalies. The largest cohort study (n=104) reported developmental delay/intellectual disability in 97% of individuals; most cases arise de novo.

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3
Pathophys.
19
Phenotypes
1
Genes
9
Treatments
1
References
1
Deep Research
⚙

Pathophysiology

3
KMT2A Loss-of-Function and Disrupted H3K4 Methylation
Wiedemann-Steiner Syndrome is caused by heterozygous loss-of-function variants in KMT2A (MLL1), which encodes a histone H3 lysine 4 (H3K4) methyltransferase that is a core component of the COMPASS-like complex. Haploinsufficiency of KMT2A disrupts chromatin organisation and reduces H3K4 methylation at developmentally regulated gene loci, including homeobox gene promoters, altering transcriptional programmes critical for neurogenesis, craniofacial development, and growth. This epigenetic dysregulation underlies the syndrome's broad developmental and somatic phenotypes.
chromatin organization link ⚠ ABNORMAL regulation of transcription by RNA polymerase II link ⚠ ABNORMAL
Show evidence (2 references)
DOI:10.1002/ajmg.a.62124 SUPPORT Human Clinical
"Wiedemann‐Steiner syndrome (WSS) is an autosomal dominant disorder caused by monoallelic variants in KMT2A and characterized by intellectual disability and hypertrichosis."
The largest multi-centre cohort confirms KMT2A monoallelic loss-of-function as the cause of WDSTS and characterises the full phenotypic spectrum.
DOI:10.1017/S1355617722000467 SUPPORT Human Clinical
"Wiedemann-Steiner syndrome (WSS) is a rare Mendelian disorder of the epigenetic machinery caused by heterozygous pathogenic variants in KMT2A."
Neuropsychology case series confirms KMT2A haploinsufficiency as the epigenetic machinery defect driving WSS neurocognitive phenotypes.
Centrosome Dysfunction and Impaired Microtubule Nucleation
In addition to its nuclear role in H3K4 methylation, KMT2A/MLL1 functions at the centrosome through its association with WDR5 and the centriolar satellite protein Cep72. The MLL/WDR5 complex localises to pericentriolar material and promotes the recruitment of γ-tubulin ring complex (γ-TuRC) components and structural proteins such as AKAP9. Loss of MLL impairs microtubule nucleation and regrowth, disrupts mitotic spindle formation, and leads to misaligned chromosomes during cell division. Patient-derived cells from WSS individuals exhibit reduced centrosomal localisation of AKAP9, NEDD1, γ-tubulin, and Cep72, and impaired microtubule nucleation, providing a cellular mechanism that may contribute to microcephaly and neurodevelopmental delay in WDSTS.
microtubule nucleation link ⚠ ABNORMAL mitotic spindle organization link ⚠ ABNORMAL
Show evidence (1 reference)
DOI:10.1126/sciadv.adn0086 SUPPORT In Vitro
"Loss of the MLL/WDR5 complex affects microtubule nucleation and regrowth. MLL/WDR5 localize to the pericentriolar material and interact with centriolar satellite protein Cep72 and γ-tubulin ring complex proteins (γ-TuRCs)."
Chodisetty et al. demonstrate in patient-derived WSS cells that KMT2A/MLL localises to centrosomes via WDR5-Cep72, and haploinsufficiency impairs microtubule nucleation—a non-nuclear mechanism contributing to neurodevelopmental pathology.
Transcriptomic and Synaptic Dysregulation in Neurons
In mouse models, Kmt2a haploinsufficiency causes reduced dendritic spine density and altered H3K4 methylation landscapes in neurons, consistent with synaptic and transcriptional defects contributing to intellectual disability and behavioural abnormalities. Double-mutant models combining Kmt2a and Kdm5c deficiency partially rescue dendritic morphology and behavioural traits, demonstrating the importance of H3K4me balance in neuronal function.
regulation of DNA-templated transcription link ⚠ ABNORMAL
Show evidence (1 reference)
DOI:10.1038/s42003-020-1001-6 SUPPORT Model Organism
"Despite opposite enzymatic activities, the two mouse models deficient for either Kmt2a or Kdm5c shared reduced dendritic spines and increased aggression. Double mutation of Kmt2a and Kdm5c clearly reversed dendritic morphology, key behavioral traits including aggression, and partially corrected..."
Vallianatos et al. demonstrate in mouse models that KMT2A loss reduces dendritic spine density and alters H3K4me landscapes, providing mechanistic insight into the intellectual disability and behavioural phenotypes of WDSTS.
●

Phenotypes

19
Cardiovascular 1
Cardiac Anomalies FREQUENT Abnormal heart morphology (HP:0001627)
Show evidence (1 reference)
DOI:10.3389/fgene.2023.1085210 SUPPORT Human Clinical
"The most frequent imaging features were patent ductus arteriosus (57.1%) and patent foramen ovale (42.9%) in cardiovascular system, and abnormal corpus callosum (50.0%) in the brain."
Lin et al. report high frequency of PDA and PFO in Chinese WDSTS patients, emphasising the importance of cardiac screening at diagnosis.
Digestive 2
Feeding Difficulties FREQUENT Feeding difficulties (HP:0011968)
Show evidence (1 reference)
DOI:10.1002/ajmg.a.62124 SUPPORT Human Clinical
"Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%)."
Feeding difficulties are present in 66.3% of the n=104 cohort, making it one of the most frequent gastrointestinal features of WDSTS.
Constipation FREQUENT Constipation (HP:0002019)
Show evidence (1 reference)
DOI:10.1002/ajmg.a.62124 SUPPORT Human Clinical
"Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%)."
Constipation is present in 63.8% of the n=104 cohort, making it the most common gastrointestinal comorbidity in WDSTS after feeding difficulties.
Eye 1
Strabismus and Ophthalmologic Anomalies OCCASIONAL Strabismus (HP:0000486)
Show evidence (1 reference)
PMID:35617449 SUPPORT Human Clinical
"Other clinical features include feeding difficulties, prenatal and postnatal growth restriction, epilepsy, ophthalmologic anomalies, congenital heart defects, hand anomalies (such as brachydactyly and clinodactyly), hypotonia, vertebral anomalies (especially fusion anomalies of the cervical..."
GeneReviews documents ophthalmologic anomalies as a recognised clinical feature of WDSTS; ophthalmologic evaluation annually is recommended.
Genitourinary 1
Genitourinary Anomalies FREQUENT Abnormality of the genitourinary system (HP:0000119)
Show evidence (1 reference)
PMID:35617449 SUPPORT Human Clinical
"Other clinical features include feeding difficulties, prenatal and postnatal growth restriction, epilepsy, ophthalmologic anomalies, congenital heart defects, hand anomalies (such as brachydactyly and clinodactyly), hypotonia, vertebral anomalies (especially fusion anomalies of the cervical..."
GeneReviews lists renal and uterine anomalies as recognised clinical features of WDSTS. The Sheppard 2021 cohort (n=104) reports renal anomalies in 28.6% and total genitourinary anomalies in 46.8%, placing this firmly in the FREQUENT range.
Immune 1
Immune Dysfunction and Recurrent Infections OCCASIONAL Recurrent infections (HP:0002719)
Show evidence (1 reference)
PMID:35617449 SUPPORT Human Clinical
"consideration of IVIG therapy in those with low antibody levels; consideration of prophylactic antibiotics in those with frequent infections"
GeneReviews recommends IVIG and prophylactic antibiotics for WDSTS individuals with immune dysfunction, confirming recurrent infections as a clinically significant and manageable comorbidity.
Musculoskeletal 3
Muscular Hypotonia FREQUENT Hypotonia (HP:0001252)
Show evidence (2 references)
DOI:10.1097/pep.0000000000000714 SUPPORT Human Clinical
"Fifty-seven percent of children diagnosed with WSS have hypotonia, and 90% have developmental delay. The diagnosis of WSS should require physical therapy services through early intervention programs due to its high correlation with motor developmental delay and disability."
Mendoza 2020 PT case study highlights the frequency of hypotonia in WSS and the need for early physical therapy. The larger Sheppard cohort reports 72.4%.
DOI:10.1002/ajmg.a.62124 SUPPORT Human Clinical
"Hypotonia was associated with loss of function (LoF) variants, and seizures were associated with non‐LoF variants."
Sheppard et al. identify a genotype-phenotype correlation: hypotonia is specifically associated with loss-of-function KMT2A variants.
Vertebral Anomalies FREQUENT Abnormality of the vertebral column (HP:0000925)
Show evidence (1 reference)
DOI:10.1002/ajmg.a.62124 SUPPORT Human Clinical
"Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%)."
Vertebral anomalies are among the most common structural comorbidities in WDSTS, present in 46.9% of the n=104 multi-centre cohort.
Scoliosis OCCASIONAL Scoliosis (HP:0002650)
Show evidence (1 reference)
PMID:35617449 SUPPORT Human Clinical
"Vertebral anomalies or scoliosis in the thoracic or lumbar spine may complicate spinal or epidural anesthesia."
GeneReviews explicitly documents scoliosis and thoracolumbar vertebral anomalies as clinically significant features in WDSTS, with anaesthetic implications. Scoliosis affects approximately 21.3% of individuals per the Sheppard cohort.
Nervous System 6
Global Developmental Delay VERY_FREQUENT Global developmental delay (HP:0001263)
Show evidence (1 reference)
DOI:10.1002/ajmg.a.62124 SUPPORT Human Clinical
"Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%)."
The Sheppard et al. n=104 multi-centre cohort provides the most robust frequency estimate (97%) for developmental delay/intellectual disability in WDSTS.
Intellectual Disability VERY_FREQUENT Intellectual disability (HP:0001249)
Show evidence (1 reference)
DOI:10.1017/S1355617722000467 SUPPORT Human Clinical
"The majority of patients performed in the below average to very low ranges in Nonverbal Reasoning, Visual/Spatial Perception, Visuoconstruction, Visual Memory, Attention, Working Memory and Math Computation skills. In contrast, over half the sample performed within normal limits on Receptive..."
Ng et al. characterise the specific neurocognitive profile of WSS in 10 patients, demonstrating nonverbal/visuospatial weaknesses with relative verbal skill sparing—informing educational planning.
Behavioral Abnormalities FREQUENT Atypical behavior (HP:0000708)
Show evidence (1 reference)
DOI:10.1017/S1355617722000467 SUPPORT Human Clinical
"Most caregivers reported deficits in executive functioning, most notably in emotion regulation."
Ng et al. identify executive function and emotion regulation deficits as a characteristic behavioural feature of WDSTS in a neuropsychological case series of 10 patients.
Seizures OCCASIONAL Seizure (HP:0001250)
Show evidence (1 reference)
DOI:10.1002/ajmg.a.62124 SUPPORT Human Clinical
"Hypotonia was associated with loss of function (LoF) variants, and seizures were associated with non‐LoF variants."
Sheppard et al. identify seizures (~20% prevalence) as associated with non-LoF (missense) KMT2A variants, providing an important genotype-phenotype correlation for clinical management.
Abnormal Corpus Callosum Morphology FREQUENT Abnormal corpus callosum morphology (HP:0001273)
Show evidence (1 reference)
DOI:10.3389/fgene.2023.1085210 SUPPORT Human Clinical
"The most frequent imaging features were patent ductus arteriosus (57.1%) and patent foramen ovale (42.9%) in cardiovascular system, and abnormal corpus callosum (50.0%) in the brain."
Lin et al. identify abnormal corpus callosum morphology in 50% of Chinese WDSTS patients on brain MRI.
Obstructive Sleep Apnea OCCASIONAL Obstructive sleep apnea (HP:0002870)
Show evidence (1 reference)
PMID:35617449 SUPPORT Human Clinical
"CPAP, BiPAP, or surgical removal of the tonsils and adenoids for those with obstructive sleep apnea"
GeneReviews includes CPAP/BiPAP and surgical adenotonsillectomy as management for OSA in WDSTS, confirming it as a recognised clinical feature warranting active screening.
Growth 2
Short Stature FREQUENT Short stature (HP:0004322)
Show evidence (2 references)
DOI:10.1002/ajmg.a.62124 SUPPORT Human Clinical
"Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%)."
Short stature is present in 57.8% of the Sheppard multi-centre cohort of 104 individuals.
DOI:10.3389/fgene.2023.1085210 SUPPORT Human Clinical
"The most common clinical features were short stature (90.9%) and developmental delay (90.9%), followed by intellectual disability (72.7%)."
Lin et al. report short stature as the most frequent feature (90.9%) in a Chinese cohort, emphasising cross-ethnic variability in phenotype frequency.
Failure to Thrive FREQUENT Failure to thrive (HP:0001508)
Show evidence (1 reference)
DOI:10.1002/ajmg.a.62124 SUPPORT Human Clinical
"Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%)."
Failure to thrive is present in 67.7% of the n=104 Sheppard cohort.
Other 2
Elbow Hypertrichosis FREQUENT Elbow hypertrichosis (HP:0004780)
Show evidence (2 references)
DOI:10.1002/ajmg.a.62124 SUPPORT Human Clinical
"Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%)."
Hypertrichosis cubiti is present in 57% of the n=104 cohort, confirming it as a frequent but not invariant hallmark of WDSTS.
DOI:10.1111/cge.13254 SUPPORT Human Clinical
"Hypertrichosis cubiti that was supposed to be pathognomonic in the literature was found only in 61% of our cases."
Baer et al. report hypertrichosis cubiti in 61% of 33 French WDSTS cases, noting it is not pathognomonic—molecular diagnosis is required.
Growth Hormone Deficiency and Pituitary Abnormalities OCCASIONAL Abnormality of the hypothalamus-pituitary axis (HP:0000864)
Show evidence (1 reference)
PMID:35617449 SUPPORT Human Clinical
"growth hormone therapy for those with growth hormone deficiency; thyroid replacement therapy for hypothyroidism"
GeneReviews recommends GH therapy and thyroid replacement for respective endocrine deficiencies, confirming the frequency and clinical significance of these endocrine comorbidities in WDSTS.
🧬

Genetic Associations

1
KMT2A (Causative)
Show evidence (2 references)
DOI:10.1002/ajmg.a.62124 SUPPORT Human Clinical
"Sixty‐nine of the 82 variants (84%) observed in the study were not previously reported in the literature."
Sheppard et al. characterise the full KMT2A variant spectrum in n=104, showing high allelic heterogeneity with predominantly novel variants.
DOI:10.1038/s41431-023-01474-x SUPPORT Human Clinical
"Remaining Cornelia de Lange syndrome, KMT2A, KDM5C and CHD7 signatures reached 70–100% sensitivity at best with unstable performances, suffering from heterogeneous methylation profiles among cases and rare discordant samples."
Husson et al. independently validate the KMT2A episignature, demonstrating its potential but also limitations (70-100% sensitivity, 100% specificity) for variant interpretation in a diagnostic setting.
💊

Treatments

9
Physical Therapy
Action: physical therapy MAXO:0000011
Early physical therapy (PT) is indicated from infancy for hypotonia and motor developmental delay. PT through early intervention programmes addresses motor milestone delays and functional disability. Orthotics and treadmill walking have been used successfully as adjuncts. Progress should be measured by functional achievement rather than norm-referenced scores alone.
Show evidence (1 reference)
DOI:10.1097/pep.0000000000000714 SUPPORT Human Clinical
"The diagnosis of WSS should require physical therapy services through early intervention programs due to its high correlation with motor developmental delay and disability."
Mendoza 2020 documents PT from birth to 3 years in a WDSTS case, demonstrating progression through developmental motor sequences with early intervention.
Speech and Language Therapy
Action: speech therapy MAXO:0000930
Speech and language therapy is indicated for the majority of individuals with WDSTS given the near-universal presence of speech delay (median age of first words 18 months in the largest cohort). Therapy targets expressive language, feeding/swallowing coordination, and pragmatic communication.
Show evidence (1 reference)
DOI:10.1002/ajmg.a.62124 SUPPORT Human Clinical
"The median ages at walking and first words were 20 months and 18 months, respectively."
The significant speech delay (median first words 18 months) in the n=104 cohort supports routine speech therapy as a core intervention in WDSTS.
Occupational Therapy
Action: occupational therapy MAXO:0001351
Occupational therapy addresses fine motor delays, visuospatial difficulties, activities of daily living, and adaptive equipment needs. The characteristic neuropsychological profile of WDSTS (nonverbal/visuospatial weaknesses) makes OT a tailored intervention for functional independence.
Behavioral and Psychiatric Management
Action: Pharmacotherapy NCIT:C15986
Management of behavioural problems including ADHD symptoms, autistic features, and emotion dysregulation with evidence-based behavioural interventions and, where clinically indicated, pharmacotherapy. Approximately 21% of individuals meet ASD diagnostic criteria, and executive function deficits are common.
Genetic Counseling
Action: genetic counseling MAXO:0000079
Genetic counselling is recommended for all families with WDSTS. Most cases are de novo (55.8% confirmed in the largest cohort), conferring low empiric recurrence risk. However, familial autosomal dominant transmission and germline mosaicism have been reported, warranting careful parental evaluation and risk stratification. Prenatal diagnosis is available for familial cases.
Show evidence (1 reference)
DOI:10.1111/cge.13254 SUPPORT Human Clinical
"We observed autosomal dominant transmission of WSS in 3 families and mosaicism in one family."
Baer et al. document both familial transmission and mosaicism in French WDSTS cases, underscoring the importance of genetic counselling including parental testing.
Growth Hormone Therapy
Action: hormone modifying therapy MAXO:0000283
Recombinant human growth hormone (rhGH) therapy has been trialled in WDSTS patients with short stature. In a Chinese cohort, two patients treated with rhGH showed satisfactory height gains, though one experienced acceleration of bone age. GH deficiency has been documented in a subset of individuals with WDSTS and should be evaluated in those with severe growth failure.
Show evidence (1 reference)
DOI:10.3389/fgene.2023.1085210 SUPPORT Human Clinical
"Two patients were treated with rhGH and yielded satisfactory height gains, but one developed acceleration of bone age."
Lin et al. report rhGH use in two WDSTS patients with short stature, showing benefit but also bone age acceleration as a potential adverse effect.
Anti-Seizure Pharmacotherapy
Action: anti-seizure pharmacotherapy Ontology label: Pharmacotherapy NCIT:C15986
Agent: lamotrigine ↗
Seizures occur in approximately 20% of WDSTS individuals, associated with non-loss-of-function KMT2A variants. Standard anti-seizure medication by an experienced neurologist is recommended. Lamotrigine has been used successfully. Valproate should be used with caution: one WDSTS individual developed hyperammonemia on valproate, and while this is not specific to WSS, GeneReviews explicitly flags it as a drug to avoid where possible.
Show evidence (1 reference)
PMID:35617449 SUPPORT Human Clinical
"The authors are aware of one individual with WSS who developed hyperammonemia with the use of the anti-seizure medication valproate. While this is not specific to individuals with WSS, valproate should be used with caution."
GeneReviews explicitly flags valproate caution in WDSTS management, making this a critical drug-safety note for clinical care of WDSTS individuals with seizures.
Immunoglobulin Replacement and Infection Prophylaxis
Action: immunomodulatory pharmacotherapy Ontology label: Pharmacotherapy NCIT:C15986
For WDSTS individuals with documented low antibody levels or immune dysfunction, IVIG therapy is recommended. Prophylactic antibiotics should be considered for those with frequent infections. Immunological evaluation is part of the standard surveillance protocol.
Show evidence (1 reference)
PMID:35617449 SUPPORT Human Clinical
"consideration of IVIG therapy in those with low antibody levels; consideration of prophylactic antibiotics in those with frequent infections"
GeneReviews recommends IVIG and prophylactic antibiotics as management for immune dysfunction in WDSTS.
Supportive Care and Multidisciplinary Management
Action: supportive care MAXO:0000950
Individuals with WDSTS benefit from multidisciplinary follow-up encompassing neurodevelopmental paediatrics, cardiology (for congenital anomalies), gastroenterology (feeding, constipation), orthopaedics (vertebral/scoliosis monitoring), ophthalmology, and immunology. Bowel management for constipation and nutritional support for feeding difficulties are routine components of care.
{ }

Source YAML

click to show 
name: Wiedemann-Steiner Syndrome
creation_date: "2026-05-16T00:00:00Z"
updated_date: "2026-05-16T12:00:00Z"
references:
  - reference: PMID:35617449
    title: "Wiedemann-Steiner Syndrome."
    tags:
      - GeneReviews
category: Mendelian
disease_term:
  preferred_term: Wiedemann-Steiner syndrome
  term:
    id: MONDO:0011518
    label: Wiedemann-Steiner syndrome

parents:
  - Intellectual disability syndrome
  - Mendelian neurodevelopmental disorder

description: >
  Wiedemann-Steiner Syndrome (WDSTS; OMIM 605130) is a rare autosomal dominant
  chromatinopathy caused by heterozygous pathogenic variants in KMT2A, encoding
  a histone H3 lysine 4 (H3K4) methyltransferase. The condition is characterised
  by global developmental delay, intellectual disability (typically mild to
  moderate), short stature, hypertrichosis (especially elbow hypertrichosis),
  characteristic craniofacial dysmorphism, and multi-system concomitants including
  gastrointestinal, skeletal, cardiac, and genitourinary anomalies. The largest
  cohort study (n=104) reported developmental delay/intellectual disability in 97%
  of individuals; most cases arise de novo.

pathophysiology:
  - name: KMT2A Loss-of-Function and Disrupted H3K4 Methylation
    description: >
      Wiedemann-Steiner Syndrome is caused by heterozygous loss-of-function variants
      in KMT2A (MLL1), which encodes a histone H3 lysine 4 (H3K4) methyltransferase
      that is a core component of the COMPASS-like complex. Haploinsufficiency of
      KMT2A disrupts chromatin organisation and reduces H3K4 methylation at
      developmentally regulated gene loci, including homeobox gene promoters,
      altering transcriptional programmes critical for neurogenesis, craniofacial
      development, and growth. This epigenetic dysregulation underlies the
      syndrome's broad developmental and somatic phenotypes.
    biological_processes:
      - preferred_term: chromatin organization
        term:
          id: GO:0006325
          label: chromatin organization
        modifier: ABNORMAL
      - preferred_term: regulation of transcription by RNA polymerase II
        term:
          id: GO:0006357
          label: regulation of transcription by RNA polymerase II
        modifier: ABNORMAL
    evidence:
      - reference: DOI:10.1002/ajmg.a.62124
        reference_title: "Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "Wiedemann‐Steiner syndrome (WSS) is an autosomal dominant disorder caused by monoallelic variants in KMT2A and characterized by intellectual disability and hypertrichosis."
        explanation: >
          The largest multi-centre cohort confirms KMT2A monoallelic loss-of-function
          as the cause of WDSTS and characterises the full phenotypic spectrum.
      - reference: DOI:10.1017/S1355617722000467
        reference_title: "Individuals with Wiedemann-Steiner syndrome show nonverbal reasoning and visuospatial defects with relative verbal skill sparing"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "Wiedemann-Steiner syndrome (WSS) is a rare Mendelian disorder of the epigenetic machinery caused by heterozygous pathogenic variants in KMT2A."
        explanation: >
          Neuropsychology case series confirms KMT2A haploinsufficiency as the
          epigenetic machinery defect driving WSS neurocognitive phenotypes.

  - name: Centrosome Dysfunction and Impaired Microtubule Nucleation
    description: >
      In addition to its nuclear role in H3K4 methylation, KMT2A/MLL1 functions
      at the centrosome through its association with WDR5 and the centriolar
      satellite protein Cep72. The MLL/WDR5 complex localises to pericentriolar
      material and promotes the recruitment of γ-tubulin ring complex (γ-TuRC)
      components and structural proteins such as AKAP9. Loss of MLL impairs
      microtubule nucleation and regrowth, disrupts mitotic spindle formation, and
      leads to misaligned chromosomes during cell division. Patient-derived cells
      from WSS individuals exhibit reduced centrosomal localisation of AKAP9,
      NEDD1, γ-tubulin, and Cep72, and impaired microtubule nucleation, providing
      a cellular mechanism that may contribute to microcephaly and neurodevelopmental
      delay in WDSTS.
    biological_processes:
      - preferred_term: microtubule nucleation
        term:
          id: GO:0007020
          label: microtubule nucleation
        modifier: ABNORMAL
      - preferred_term: mitotic spindle organization
        term:
          id: GO:0007052
          label: mitotic spindle organization
        modifier: ABNORMAL
    evidence:
      - reference: DOI:10.1126/sciadv.adn0086
        reference_title: "MLL/WDR5 complex recruits centriolar satellite protein Cep72 to regulate microtubule nucleation and spindle formation"
        supports: SUPPORT
        evidence_source: IN_VITRO
        snippet: "Loss of the MLL/WDR5 complex affects microtubule nucleation and regrowth. MLL/WDR5 localize to the pericentriolar material and interact with centriolar satellite protein Cep72 and γ-tubulin ring complex proteins (γ-TuRCs)."
        explanation: >
          Chodisetty et al. demonstrate in patient-derived WSS cells that KMT2A/MLL
          localises to centrosomes via WDR5-Cep72, and haploinsufficiency impairs
          microtubule nucleation—a non-nuclear mechanism contributing to
          neurodevelopmental pathology.

  - name: Transcriptomic and Synaptic Dysregulation in Neurons
    description: >
      In mouse models, Kmt2a haploinsufficiency causes reduced dendritic spine
      density and altered H3K4 methylation landscapes in neurons, consistent with
      synaptic and transcriptional defects contributing to intellectual disability
      and behavioural abnormalities. Double-mutant models combining Kmt2a and
      Kdm5c deficiency partially rescue dendritic morphology and behavioural traits,
      demonstrating the importance of H3K4me balance in neuronal function.
    biological_processes:
      - preferred_term: regulation of DNA-templated transcription
        term:
          id: GO:0006355
          label: regulation of DNA-templated transcription
        modifier: ABNORMAL
    evidence:
      - reference: DOI:10.1038/s42003-020-1001-6
        reference_title: "Mutually suppressive roles of KMT2A and KDM5C in behaviour, neuronal structure, and histone H3K4 methylation"
        supports: SUPPORT
        evidence_source: MODEL_ORGANISM
        snippet: "Despite opposite enzymatic activities, the two mouse models deficient for either Kmt2a or Kdm5c shared reduced dendritic spines and increased aggression. Double mutation of Kmt2a and Kdm5c clearly reversed dendritic morphology, key behavioral traits including aggression, and partially corrected altered transcriptomes and H3K4me landscapes."
        explanation: >
          Vallianatos et al. demonstrate in mouse models that KMT2A loss reduces
          dendritic spine density and alters H3K4me landscapes, providing mechanistic
          insight into the intellectual disability and behavioural phenotypes of WDSTS.

phenotypes:
  - name: Global Developmental Delay
    description: >
      Global developmental delay is present in virtually all individuals with WDSTS
      (97% in the largest cohort). Median age at first words is 18 months and
      independent walking is achieved at a median of 20 months, with ranges
      extending to 60 months. Motor delay is a consistent early feature.
    category: Neurological
    frequency: VERY_FREQUENT
    phenotype_term:
      preferred_term: Global developmental delay
      term:
        id: HP:0001263
        label: Global developmental delay
    evidence:
      - reference: DOI:10.1002/ajmg.a.62124
        reference_title: "Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%)."
        explanation: >
          The Sheppard et al. n=104 multi-centre cohort provides the most robust
          frequency estimate (97%) for developmental delay/intellectual disability
          in WDSTS.

  - name: Intellectual Disability
    description: >
      Mild to moderate intellectual disability is present in the majority of
      individuals with WDSTS. Neuropsychological profiling reveals a characteristic
      pattern of prominent nonverbal reasoning and visuospatial deficits with
      relative sparing of receptive vocabulary and verbal memory. In a specialized
      chromatin clinic cohort, cognitive impairment was distributed as: borderline
      21.4%, mild ID 57.1%, moderate ID 21.4%.
    category: Neurological
    frequency: VERY_FREQUENT
    phenotype_term:
      preferred_term: Intellectual disability
      term:
        id: HP:0001249
        label: Intellectual disability
    evidence:
      - reference: DOI:10.1017/S1355617722000467
        reference_title: "Individuals with Wiedemann-Steiner syndrome show nonverbal reasoning and visuospatial defects with relative verbal skill sparing"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "The majority of patients performed in the below average to very low ranges in Nonverbal Reasoning, Visual/Spatial Perception, Visuoconstruction, Visual Memory, Attention, Working Memory and Math Computation skills. In contrast, over half the sample performed within normal limits on Receptive Vocabulary, Verbal Memory, and Word Reading."
        explanation: >
          Ng et al. characterise the specific neurocognitive profile of WSS in 10
          patients, demonstrating nonverbal/visuospatial weaknesses with relative
          verbal skill sparing—informing educational planning.

  - name: Muscular Hypotonia
    description: >
      Hypotonia is present in approximately 72% of WDSTS individuals and is
      significantly associated with loss-of-function (LoF) variants in KMT2A.
      It contributes to delayed motor milestones and feeding difficulties in infancy.
      Early physical therapy targeting hypotonia and motor delay is recommended.
    category: Neurological
    frequency: FREQUENT
    phenotype_term:
      preferred_term: Hypotonia
      term:
        id: HP:0001252
        label: Hypotonia
    evidence:
      - reference: DOI:10.1097/pep.0000000000000714
        reference_title: "Physical Therapy Management of Wiedemann-Steiner Syndrome From Birth to 3 Years"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "Fifty-seven percent of children diagnosed with WSS have hypotonia, and 90% have developmental delay. The diagnosis of WSS should require physical therapy services through early intervention programs due to its high correlation with motor developmental delay and disability."
        explanation: >
          Mendoza 2020 PT case study highlights the frequency of hypotonia in WSS
          and the need for early physical therapy. The larger Sheppard cohort reports 72.4%.
      - reference: DOI:10.1002/ajmg.a.62124
        reference_title: "Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "Hypotonia was associated with loss of function (LoF) variants, and seizures were associated with non‐LoF variants."
        explanation: >
          Sheppard et al. identify a genotype-phenotype correlation: hypotonia is
          specifically associated with loss-of-function KMT2A variants.

  - name: Short Stature
    description: >
      Postnatal growth deficiency and short stature are present in approximately
      57-81% of individuals depending on cohort. In Chinese patients, short stature
      was the most common feature (90.9%). Growth hormone deficiency has been
      reported in a subset, and recombinant human growth hormone (rhGH) therapy
      has produced satisfactory height gains in some patients.
    category: Growth
    frequency: FREQUENT
    phenotype_term:
      preferred_term: Short stature
      term:
        id: HP:0004322
        label: Short stature
    evidence:
      - reference: DOI:10.1002/ajmg.a.62124
        reference_title: "Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%)."
        explanation: >
          Short stature is present in 57.8% of the Sheppard multi-centre cohort
          of 104 individuals.
      - reference: DOI:10.3389/fgene.2023.1085210
        reference_title: "Novel variants and phenotypic heterogeneity in a cohort of 11 Chinese children with Wiedemann-Steiner syndrome"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "The most common clinical features were short stature (90.9%) and developmental delay (90.9%), followed by intellectual disability (72.7%)."
        explanation: >
          Lin et al. report short stature as the most frequent feature (90.9%) in
          a Chinese cohort, emphasising cross-ethnic variability in phenotype frequency.

  - name: Elbow Hypertrichosis
    description: >
      Hypertrichosis, particularly involving the elbows (hypertrichosis cubiti), is
      a hallmark feature of WDSTS, reported in 57-61% of cohort participants. It
      was originally considered pathognomonic but is absent in approximately 39-43%
      of cases, including molecularly confirmed diagnoses. Generalised hypertrichosis
      may also occur.
    category: Integument
    frequency: FREQUENT
    phenotype_term:
      preferred_term: Elbow hypertrichosis
      term:
        id: HP:0004780
        label: Elbow hypertrichosis
    evidence:
      - reference: DOI:10.1002/ajmg.a.62124
        reference_title: "Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%)."
        explanation: >
          Hypertrichosis cubiti is present in 57% of the n=104 cohort, confirming
          it as a frequent but not invariant hallmark of WDSTS.
      - reference: DOI:10.1111/cge.13254
        reference_title: "Wiedemann-Steiner syndrome as a major cause of syndromic intellectual disability: A study of 33 French cases"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "Hypertrichosis cubiti that was supposed to be pathognomonic in the literature was found only in 61% of our cases."
        explanation: >
          Baer et al. report hypertrichosis cubiti in 61% of 33 French WDSTS cases,
          noting it is not pathognomonic—molecular diagnosis is required.

  - name: Feeding Difficulties
    description: >
      Feeding difficulties are reported in approximately 66% of WDSTS individuals
      and contribute to failure to thrive in infancy. Approximately 25% require
      nasogastric or gastrostomy tube feeding at some point. Hypotonia and
      oropharyngeal coordination difficulties are the primary contributing factors.
    category: Gastrointestinal
    frequency: FREQUENT
    phenotype_term:
      preferred_term: Feeding difficulties
      term:
        id: HP:0011968
        label: Feeding difficulties
    evidence:
      - reference: DOI:10.1002/ajmg.a.62124
        reference_title: "Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%)."
        explanation: >
          Feeding difficulties are present in 66.3% of the n=104 cohort, making
          it one of the most frequent gastrointestinal features of WDSTS.

  - name: Failure to Thrive
    description: >
      Failure to thrive is reported in approximately 68% of WDSTS individuals,
      reflecting the combined impact of feeding difficulties, hypotonia, and
      growth deficiency in infancy and early childhood.
    category: Growth
    frequency: FREQUENT
    phenotype_term:
      preferred_term: Failure to thrive
      term:
        id: HP:0001508
        label: Failure to thrive
    evidence:
      - reference: DOI:10.1002/ajmg.a.62124
        reference_title: "Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%)."
        explanation: >
          Failure to thrive is present in 67.7% of the n=104 Sheppard cohort.

  - name: Constipation
    description: >
      Chronic constipation is a frequent gastrointestinal comorbidity of WDSTS,
      reported in approximately 64% of individuals. The aetiology is likely
      multifactorial, involving hypotonia-related dysmotility and dietary factors.
      Proactive bowel management is an important aspect of care.
    category: Gastrointestinal
    frequency: FREQUENT
    phenotype_term:
      preferred_term: Constipation
      term:
        id: HP:0002019
        label: Constipation
    evidence:
      - reference: DOI:10.1002/ajmg.a.62124
        reference_title: "Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%)."
        explanation: >
          Constipation is present in 63.8% of the n=104 cohort, making it the
          most common gastrointestinal comorbidity in WDSTS after feeding difficulties.

  - name: Behavioral Abnormalities
    description: >
      Behavioural issues including hyperactivity, attention deficit, autistic
      features (21.3% meet ASD criteria in the largest cohort), and executive
      function deficits are frequently reported. Caregivers specifically report
      difficulties in emotion regulation. The behavioural phenotype overlaps with
      Kabuki syndrome (KMT2D), suggesting shared hippocampal neurogenesis pathways.
    category: Psychiatric
    frequency: FREQUENT
    phenotype_term:
      preferred_term: Atypical behavior
      term:
        id: HP:0000708
        label: Atypical behavior
    evidence:
      - reference: DOI:10.1017/S1355617722000467
        reference_title: "Individuals with Wiedemann-Steiner syndrome show nonverbal reasoning and visuospatial defects with relative verbal skill sparing"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "Most caregivers reported deficits in executive functioning, most notably in emotion regulation."
        explanation: >
          Ng et al. identify executive function and emotion regulation deficits as
          a characteristic behavioural feature of WDSTS in a neuropsychological
          case series of 10 patients.

  - name: Vertebral Anomalies
    description: >
      Vertebral anomalies are present in approximately 47% of WDSTS individuals,
      including fusion anomalies of the cervical spine and other structural
      defects. Cervical spine anomalies may lead to immobility or instability
      and can complicate airway management during anaesthesia. Orthopaedic
      monitoring is recommended.
    category: Musculoskeletal
    frequency: FREQUENT
    phenotype_term:
      preferred_term: Abnormality of the vertebral column
      term:
        id: HP:0000925
        label: Abnormality of the vertebral column
    evidence:
      - reference: DOI:10.1002/ajmg.a.62124
        reference_title: "Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%)."
        explanation: >
          Vertebral anomalies are among the most common structural comorbidities
          in WDSTS, present in 46.9% of the n=104 multi-centre cohort.

  - name: Scoliosis
    description: >
      Scoliosis is present in approximately 21% of WDSTS individuals and
      is distinct from the broader category of vertebral anomalies (47%).
      Scoliosis warrants orthopaedic monitoring and may require intervention
      in progressive cases.
    category: Musculoskeletal
    frequency: OCCASIONAL
    phenotype_term:
      preferred_term: Scoliosis
      term:
        id: HP:0002650
        label: Scoliosis
    evidence:
      - reference: PMID:35617449
        reference_title: "Wiedemann-Steiner Syndrome."
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "Vertebral anomalies or scoliosis in the thoracic or lumbar spine may complicate spinal or epidural anesthesia."
        explanation: >
          GeneReviews explicitly documents scoliosis and thoracolumbar vertebral
          anomalies as clinically significant features in WDSTS, with anaesthetic
          implications. Scoliosis affects approximately 21.3% of individuals per
          the Sheppard cohort.

  - name: Seizures
    description: >
      Seizures occur in approximately 20% of WDSTS individuals and are
      significantly associated with non-loss-of-function (missense/non-LoF) KMT2A
      variants, representing a genotype-phenotype correlation. Anti-epileptic
      management follows standard protocols.
    category: Neurological
    frequency: OCCASIONAL
    phenotype_term:
      preferred_term: Seizures
      term:
        id: HP:0001250
        label: Seizure
    evidence:
      - reference: DOI:10.1002/ajmg.a.62124
        reference_title: "Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "Hypotonia was associated with loss of function (LoF) variants, and seizures were associated with non‐LoF variants."
        explanation: >
          Sheppard et al. identify seizures (~20% prevalence) as associated with
          non-LoF (missense) KMT2A variants, providing an important genotype-phenotype
          correlation for clinical management.

  - name: Cardiac Anomalies
    description: >
      Congenital cardiac anomalies are present in approximately 36% of WDSTS
      individuals. In Chinese cohorts, patent ductus arteriosus (PDA, 57.1%) and
      patent foramen ovale (PFO, 42.9%) are particularly frequent cardiac findings.
      Cardiac evaluation at diagnosis is recommended.
    category: Cardiovascular
    frequency: FREQUENT
    phenotype_term:
      preferred_term: Congenital cardiac anomaly
      term:
        id: HP:0001627
        label: Abnormal heart morphology
    evidence:
      - reference: DOI:10.3389/fgene.2023.1085210
        reference_title: "Novel variants and phenotypic heterogeneity in a cohort of 11 Chinese children with Wiedemann-Steiner syndrome"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "The most frequent imaging features were patent ductus arteriosus (57.1%) and patent foramen ovale (42.9%) in cardiovascular system, and abnormal corpus callosum (50.0%) in the brain."
        explanation: >
          Lin et al. report high frequency of PDA and PFO in Chinese WDSTS patients,
          emphasising the importance of cardiac screening at diagnosis.

  - name: Abnormal Corpus Callosum Morphology
    description: >
      Brain structural anomalies, particularly affecting the corpus callosum, are
      found in approximately 50% of WDSTS individuals in imaging studies. These
      anomalies likely contribute to the cognitive and behavioural phenotypes.
    category: Neurological
    frequency: FREQUENT
    phenotype_term:
      preferred_term: Abnormal corpus callosum morphology
      term:
        id: HP:0001273
        label: Abnormal corpus callosum morphology
    evidence:
      - reference: DOI:10.3389/fgene.2023.1085210
        reference_title: "Novel variants and phenotypic heterogeneity in a cohort of 11 Chinese children with Wiedemann-Steiner syndrome"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "The most frequent imaging features were patent ductus arteriosus (57.1%) and patent foramen ovale (42.9%) in cardiovascular system, and abnormal corpus callosum (50.0%) in the brain."
        explanation: >
          Lin et al. identify abnormal corpus callosum morphology in 50% of
          Chinese WDSTS patients on brain MRI.

  - name: Strabismus and Ophthalmologic Anomalies
    description: >
      Ophthalmologic anomalies are reported in 18-32% of WDSTS individuals,
      including strabismus, astigmatism, blepharoptosis (ptosis), myopia,
      hyperopia, and amblyopia. Ptosis may require oculoplastic surgical
      intervention. Annual ophthalmologic evaluation is recommended.
    category: Ophthalmological
    frequency: OCCASIONAL
    phenotype_term:
      preferred_term: Strabismus
      term:
        id: HP:0000486
        label: Strabismus
    evidence:
      - reference: PMID:35617449
        reference_title: "Wiedemann-Steiner Syndrome."
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "Other clinical features include feeding difficulties, prenatal and postnatal growth restriction, epilepsy, ophthalmologic anomalies, congenital heart defects, hand anomalies (such as brachydactyly and clinodactyly), hypotonia, vertebral anomalies (especially fusion anomalies of the cervical spine), renal and uterine anomalies, immune dysfunction, brain malformations, and dental anomalies."
        explanation: >
          GeneReviews documents ophthalmologic anomalies as a recognised clinical
          feature of WDSTS; ophthalmologic evaluation annually is recommended.

  - name: Obstructive Sleep Apnea
    description: >
      Obstructive sleep apnea (OSA) occurs in approximately 25% of WDSTS
      individuals, likely related to hypotonia and craniofacial features.
      Tonsillectomy/adenoidectomy accounts for approximately 20% of those
      with OSA. CPAP, BiPAP, or surgical adenotonsillectomy are the primary
      management approaches.
    category: Respiratory
    frequency: OCCASIONAL
    phenotype_term:
      preferred_term: Obstructive sleep apnea
      term:
        id: HP:0002870
        label: Obstructive sleep apnea
    evidence:
      - reference: PMID:35617449
        reference_title: "Wiedemann-Steiner Syndrome."
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "CPAP, BiPAP, or surgical removal of the tonsils and adenoids for those with obstructive sleep apnea"
        explanation: >
          GeneReviews includes CPAP/BiPAP and surgical adenotonsillectomy as
          management for OSA in WDSTS, confirming it as a recognised clinical
          feature warranting active screening.

  - name: Immune Dysfunction and Recurrent Infections
    description: >
      Immune dysfunction is documented in 21-54% of WDSTS individuals.
      In a tested subset, abnormal immunoglobulin levels were found in 53.8%
      and insufficient pneumococcal vaccine response in 30.8%. Recurrent
      infections occur in approximately 21% overall. Management includes
      consideration of IVIG for low antibody levels and prophylactic antibiotics
      for frequent infections.
    category: Immunological
    frequency: OCCASIONAL
    phenotype_term:
      preferred_term: Recurrent infections
      term:
        id: HP:0002719
        label: Recurrent infections
    evidence:
      - reference: PMID:35617449
        reference_title: "Wiedemann-Steiner Syndrome."
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "consideration of IVIG therapy in those with low antibody levels; consideration of prophylactic antibiotics in those with frequent infections"
        explanation: >
          GeneReviews recommends IVIG and prophylactic antibiotics for WDSTS
          individuals with immune dysfunction, confirming recurrent infections
          as a clinically significant and manageable comorbidity.

  - name: Genitourinary Anomalies
    description: >
      Genitourinary anomalies are present in approximately 47% of WDSTS individuals,
      including renal anomalies (28.6%, e.g. vesicoureteral reflux, hydronephrosis),
      uterine anomalies in females, and cryptorchidism in males. This makes
      genitourinary involvement one of the most frequent non-neurological organ
      systems affected in WDSTS. Renal ultrasound and urological evaluation are
      recommended as part of the diagnostic work-up.
    category: Genitourinary
    frequency: FREQUENT
    phenotype_term:
      preferred_term: Abnormality of the genitourinary system
      term:
        id: HP:0000119
        label: Abnormality of the genitourinary system
    evidence:
      - reference: PMID:35617449
        reference_title: "Wiedemann-Steiner Syndrome."
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "Other clinical features include feeding difficulties, prenatal and postnatal growth restriction, epilepsy, ophthalmologic anomalies, congenital heart defects, hand anomalies (such as brachydactyly and clinodactyly), hypotonia, vertebral anomalies (especially fusion anomalies of the cervical spine), renal and uterine anomalies, immune dysfunction, brain malformations, and dental anomalies."
        explanation: >
          GeneReviews lists renal and uterine anomalies as recognised clinical
          features of WDSTS. The Sheppard 2021 cohort (n=104) reports renal
          anomalies in 28.6% and total genitourinary anomalies in 46.8%,
          placing this firmly in the FREQUENT range.

  - name: Growth Hormone Deficiency and Pituitary Abnormalities
    description: >
      Growth hormone deficiency occurs in a subset of WDSTS individuals, and
      pituitary gland abnormalities may be identified on MRI in some cases.
      Premature adrenarche has also been reported. These endocrine comorbidities
      contribute to short stature and warrant endocrinological evaluation, with
      growth hormone therapy indicated for confirmed GH deficiency.
    category: Endocrine
    frequency: OCCASIONAL
    phenotype_term:
      preferred_term: Growth hormone deficiency
      term:
        id: HP:0000864
        label: Abnormality of the hypothalamus-pituitary axis
    evidence:
      - reference: PMID:35617449
        reference_title: "Wiedemann-Steiner Syndrome."
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "growth hormone therapy for those with growth hormone deficiency; thyroid replacement therapy for hypothyroidism"
        explanation: >
          GeneReviews recommends GH therapy and thyroid replacement for respective
          endocrine deficiencies, confirming the frequency and clinical significance
          of these endocrine comorbidities in WDSTS.

genetic:
  - name: KMT2A
    notes: >
      Heterozygous pathogenic variants in KMT2A (lysine methyltransferase 2A,
      formerly MLL1) on chromosome 11q23.3. In the largest cohort (n=104, 82
      distinct variants), variant types include: frameshift 37.8%, nonsense 29.3%,
      missense 20.7%, splice-site 11%. 80/82 variants were absent from gnomAD
      v2.1.1. De novo origin confirmed in 55.8% (likely an underestimate due to
      incomplete parental testing); familial autosomal dominant transmission and
      germline mosaicism occur rarely. Genotype-phenotype correlations: hypotonia
      associates with loss-of-function variants; seizures associate with non-LoF
      (missense) variants. A genome-wide DNA methylation episignature can assist
      variant classification (70-100% sensitivity, 100% specificity in independent
      validation).
    gene_term:
      preferred_term: KMT2A
      term:
        id: hgnc:7132
        label: KMT2A
    association: Causative
    evidence:
      - reference: DOI:10.1002/ajmg.a.62124
        reference_title: "Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "Sixty‐nine of the 82 variants (84%) observed in the study were not previously reported in the literature."
        explanation: >
          Sheppard et al. characterise the full KMT2A variant spectrum in n=104,
          showing high allelic heterogeneity with predominantly novel variants.
      - reference: DOI:10.1038/s41431-023-01474-x
        reference_title: "Episignatures in practice: independent evaluation of published episignatures for the molecular diagnostics of ten neurodevelopmental disorders"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "Remaining Cornelia de Lange syndrome, KMT2A, KDM5C and CHD7 signatures reached 70–100% sensitivity at best with unstable performances, suffering from heterogeneous methylation profiles among cases and rare discordant samples."
        explanation: >
          Husson et al. independently validate the KMT2A episignature, demonstrating
          its potential but also limitations (70-100% sensitivity, 100% specificity)
          for variant interpretation in a diagnostic setting.

treatments:
  - name: Physical Therapy
    description: >
      Early physical therapy (PT) is indicated from infancy for hypotonia and
      motor developmental delay. PT through early intervention programmes addresses
      motor milestone delays and functional disability. Orthotics and treadmill
      walking have been used successfully as adjuncts. Progress should be measured
      by functional achievement rather than norm-referenced scores alone.
    treatment_term:
      preferred_term: physical therapy
      term:
        id: MAXO:0000011
        label: physical therapy
    evidence:
      - reference: DOI:10.1097/pep.0000000000000714
        reference_title: "Physical Therapy Management of Wiedemann-Steiner Syndrome From Birth to 3 Years"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "The diagnosis of WSS should require physical therapy services through early intervention programs due to its high correlation with motor developmental delay and disability."
        explanation: >
          Mendoza 2020 documents PT from birth to 3 years in a WDSTS case,
          demonstrating progression through developmental motor sequences with
          early intervention.

  - name: Speech and Language Therapy
    description: >
      Speech and language therapy is indicated for the majority of individuals
      with WDSTS given the near-universal presence of speech delay (median age
      of first words 18 months in the largest cohort). Therapy targets expressive
      language, feeding/swallowing coordination, and pragmatic communication.
    treatment_term:
      preferred_term: speech therapy
      term:
        id: MAXO:0000930
        label: speech therapy
    evidence:
      - reference: DOI:10.1002/ajmg.a.62124
        reference_title: "Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "The median ages at walking and first words were 20 months and 18 months, respectively."
        explanation: >
          The significant speech delay (median first words 18 months) in the n=104
          cohort supports routine speech therapy as a core intervention in WDSTS.

  - name: Occupational Therapy
    description: >
      Occupational therapy addresses fine motor delays, visuospatial difficulties,
      activities of daily living, and adaptive equipment needs. The characteristic
      neuropsychological profile of WDSTS (nonverbal/visuospatial weaknesses)
      makes OT a tailored intervention for functional independence.
    treatment_term:
      preferred_term: occupational therapy
      term:
        id: MAXO:0001351
        label: occupational therapy

  - name: Behavioral and Psychiatric Management
    description: >
      Management of behavioural problems including ADHD symptoms, autistic
      features, and emotion dysregulation with evidence-based behavioural
      interventions and, where clinically indicated, pharmacotherapy. Approximately
      21% of individuals meet ASD diagnostic criteria, and executive function
      deficits are common.
    treatment_term:
      preferred_term: Pharmacotherapy
      term:
        id: NCIT:C15986
        label: Pharmacotherapy

  - name: Genetic Counseling
    description: >
      Genetic counselling is recommended for all families with WDSTS. Most cases
      are de novo (55.8% confirmed in the largest cohort), conferring low empiric
      recurrence risk. However, familial autosomal dominant transmission and germline
      mosaicism have been reported, warranting careful parental evaluation and
      risk stratification. Prenatal diagnosis is available for familial cases.
    treatment_term:
      preferred_term: genetic counseling
      term:
        id: MAXO:0000079
        label: genetic counseling
    evidence:
      - reference: DOI:10.1111/cge.13254
        reference_title: "Wiedemann-Steiner syndrome as a major cause of syndromic intellectual disability: A study of 33 French cases"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "We observed autosomal dominant transmission of WSS in 3 families and mosaicism in one family."
        explanation: >
          Baer et al. document both familial transmission and mosaicism in French
          WDSTS cases, underscoring the importance of genetic counselling including
          parental testing.

  - name: Growth Hormone Therapy
    description: >
      Recombinant human growth hormone (rhGH) therapy has been trialled in WDSTS
      patients with short stature. In a Chinese cohort, two patients treated with
      rhGH showed satisfactory height gains, though one experienced acceleration
      of bone age. GH deficiency has been documented in a subset of individuals
      with WDSTS and should be evaluated in those with severe growth failure.
    treatment_term:
      preferred_term: hormone modifying therapy
      term:
        id: MAXO:0000283
        label: hormone modifying therapy
    evidence:
      - reference: DOI:10.3389/fgene.2023.1085210
        reference_title: "Novel variants and phenotypic heterogeneity in a cohort of 11 Chinese children with Wiedemann-Steiner syndrome"
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "Two patients were treated with rhGH and yielded satisfactory height gains, but one developed acceleration of bone age."
        explanation: >
          Lin et al. report rhGH use in two WDSTS patients with short stature,
          showing benefit but also bone age acceleration as a potential adverse effect.

  - name: Anti-Seizure Pharmacotherapy
    description: >
      Seizures occur in approximately 20% of WDSTS individuals, associated with
      non-loss-of-function KMT2A variants. Standard anti-seizure medication by an
      experienced neurologist is recommended. Lamotrigine has been used
      successfully. Valproate should be used with caution: one WDSTS individual
      developed hyperammonemia on valproate, and while this is not specific to
      WSS, GeneReviews explicitly flags it as a drug to avoid where possible.
    treatment_term:
      preferred_term: anti-seizure pharmacotherapy
      term:
        id: NCIT:C15986
        label: Pharmacotherapy
      therapeutic_agent:
        - preferred_term: lamotrigine
          term:
            id: CHEBI:6367
            label: lamotrigine
    evidence:
      - reference: PMID:35617449
        reference_title: "Wiedemann-Steiner Syndrome."
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "The authors are aware of one individual with WSS who developed hyperammonemia with the use of the anti-seizure medication valproate. While this is not specific to individuals with WSS, valproate should be used with caution."
        explanation: >
          GeneReviews explicitly flags valproate caution in WDSTS management,
          making this a critical drug-safety note for clinical care of WDSTS
          individuals with seizures.

  - name: Immunoglobulin Replacement and Infection Prophylaxis
    description: >
      For WDSTS individuals with documented low antibody levels or immune
      dysfunction, IVIG therapy is recommended. Prophylactic antibiotics
      should be considered for those with frequent infections. Immunological
      evaluation is part of the standard surveillance protocol.
    treatment_term:
      preferred_term: immunomodulatory pharmacotherapy
      term:
        id: NCIT:C15986
        label: Pharmacotherapy
    evidence:
      - reference: PMID:35617449
        reference_title: "Wiedemann-Steiner Syndrome."
        supports: SUPPORT
        evidence_source: HUMAN_CLINICAL
        snippet: "consideration of IVIG therapy in those with low antibody levels; consideration of prophylactic antibiotics in those with frequent infections"
        explanation: >
          GeneReviews recommends IVIG and prophylactic antibiotics as management
          for immune dysfunction in WDSTS.

  - name: Supportive Care and Multidisciplinary Management
    description: >
      Individuals with WDSTS benefit from multidisciplinary follow-up encompassing
      neurodevelopmental paediatrics, cardiology (for congenital anomalies),
      gastroenterology (feeding, constipation), orthopaedics (vertebral/scoliosis
      monitoring), ophthalmology, and immunology. Bowel management for constipation
      and nutritional support for feeding difficulties are routine components of care.
    treatment_term:
      preferred_term: supportive care
      term:
        id: MAXO:0000950
        label: supportive care
📚

References & Deep Research

References

1
PMID:35617449
Wiedemann-Steiner Syndrome.
No top-level findings curated for this source.

Deep Research

1
Falcon ▸
Wiedemann–Steiner Syndrome (WSS; KMT2A-related) — Disease Characteristics Research Report
Edison Scientific Literature 40 citations 2026-05-16T19:22:53.897266

Wiedemann–Steiner Syndrome (WSS; KMT2A-related) — Disease Characteristics Research Report

Executive Summary

Wiedemann–Steiner syndrome (WSS; also written WDSTS) is an autosomal-dominant Mendelian neurodevelopmental disorder caused primarily by heterozygous pathogenic variants in KMT2A (also known historically as MLL), a histone H3 lysine 4 (H3K4) methyltransferase and core component of the epigenetic “writer” machinery. Clinically, WSS features global developmental delay/intellectual disability, postnatal growth deficiency/short stature, hypertrichosis (often including hypertrichosis cubiti), and characteristic craniofacial dysmorphism, with frequent gastrointestinal, skeletal, cardiac, genitourinary, endocrine, and immune comorbidities in cohort studies. The largest multi-continental cohort (n=104) provides robust phenotype frequencies and milestone distributions; recent (2023–2024) advances emphasize neurocognitive profiling, and clinical implementation of DNA methylation episignatures as functional biomarkers for variant interpretation.

Key quantitative points (largest cohort, n=104): developmental delay/intellectual disability 97%, hypotonia 72.4%, failure to thrive 67.7%, feeding difficulties 66.3%, constipation 63.8%, short stature 57.8%, hypertrichosis cubiti 57%, seizures ~20%, cardiac abnormalities ~35.8% among those evaluated; median milestone ages: first words 18 months, independent walking 20 months. (sheppard2021expandingthegenotypic pages 3-4, sheppard2021expandingthegenotypic pages 11-13, sheppard2021expandingthegenotypic pages 6-11)

1. Disease Information

1.1 Concise overview

WSS is a rare autosomal-dominant disorder of the epigenetic machinery (a “chromatinopathy/MDEM”) caused by heterozygous pathogenic variants in KMT2A, characterized by neurodevelopmental impairment (developmental delay/intellectual disability), hypertrichosis (often including hypertrichosis cubiti), facial dysmorphism, and growth deficiency with multi-system congenital anomalies. (ng2023individualswithwiedemannsteiner pages 1-2, foroutan2022clinicalutilityof pages 2-3)

Recent clinical neuropsychology evidence (2023) indicates a characteristic cognitive pattern with prominent nonverbal/visuospatial weaknesses and relative sparing of some verbal skills in a pediatric series, supporting syndrome-specific educational planning. (ng2023individualswithwiedemannsteiner pages 1-2)

1.2 Key identifiers

  • MONDO: MONDO_0011518 (OpenTargets disease identifier) (OpenTargets Search: Wiedemann-Steiner syndrome-KMT2A)
  • OMIM (phenotype): 605130 (explicitly cited in neuropsychology and chromatin clinic literature) (ng2023individualswithwiedemannsteiner pages 1-2, harris2024fiveyearsof pages 7-9)
  • Causal gene: KMT2A (lysine methyltransferase 2A; H3K4 methyltransferase; 11q23 locus referenced across studies) (foroutan2022clinicalutilityof pages 2-3, lin2023novelvariantsand pages 2-3)

Not available in retrieved evidence (tool-limited): Orphanet ID, MeSH descriptor ID, ICD-10/ICD-11 mappings. These should be added from OMIM/Orphanet/ICD resources directly.

1.3 Synonyms / alternative names

  • Wiedemann–Steiner syndrome (WSS)
  • Wiedemann-Steiner syndrome (WDSTS)
  • KMT2A-related syndrome (often used in epigenetic/episignature literature) (foroutan2022clinicalutilityof pages 2-3)

1.4 Evidence provenance

The report draws primarily from: - Aggregated cohort studies (e.g., Sheppard et al. multicenter cohort of 104 individuals) (sheppard2021expandingthegenotypic pages 3-4, sheppard2021expandingthegenotypic pages 11-13, sheppard2021expandingthegenotypic pages 6-11) - Disease-focused reviews/case series (e.g., Yu et al. 2022 review; Ng et al. 2023 neuropsychology case series) (yu2022wiedemann–steinersyndromecase pages 7-8, ng2023individualswithwiedemannsteiner pages 1-2) - Clinical diagnostic-method studies (e.g., DNA methylation episignature validation papers) (foroutan2022clinicalutilityof pages 2-3, husson2024episignaturesinpractice pages 1-2) - Real-world specialized clinic cohort (Johns Hopkins Epigenetics and Chromatin Clinic experience) (harris2024fiveyearsof pages 7-9, harris2024fiveyearsof pages 5-7)

2. Etiology

2.1 Disease causal factors

Primary cause: Germline heterozygous pathogenic variants in KMT2A leading predominantly to haploinsufficiency (loss-of-function via premature stop codons and/or nonsense-mediated decay is emphasized in reviews and cohort studies). (yu2022wiedemann–steinersyndromecase pages 1-2, sheppard2021expandingthegenotypic pages 4-6)

Direct abstract quote (diagnostic episignature paper): “Wiedemann–Steiner syndrome (WDSTS) is a Mendelian syndromic intellectual disability (ID) condition… caused by pathogenic variants in the KMT2A gene.” (foroutan2022clinicalutilityof pages 2-3)

2.2 Risk factors

For a monogenic, typically de novo disorder, “risk factors” are primarily genetic and reproductive: - De novo occurrence is common. In the 104-person cohort, 55.8% were confirmed de novo (likely an underestimate due to incomplete parental testing). (sheppard2021expandingthegenotypic pages 6-11) - Familial transmission and mosaicism occur but are uncommon. Baer et al. reported autosomal-dominant transmission in three families and mosaicism in one family. (baer2018wiedemann‐steinersyndromeas pages 1-2)

Environmental risk factors are not established in the retrieved literature.

2.3 Protective factors / gene–environment interactions

No validated protective variants or gene–environment interactions specific to WSS were identified in the retrieved evidence.

3. Phenotypes

3.1 Core phenotype spectrum and frequencies

The largest available cohort data (n=104) provide the most stable frequency estimates: - Neurodevelopmental: developmental delay/intellectual disability 97%; hypotonia 72.4%; autism spectrum disorder 21.3%; seizures 20.0% (surveyed subset). (sheppard2021expandingthegenotypic pages 3-4, sheppard2021expandingthegenotypic pages 6-11) - Growth/nutrition: failure to thrive 67.7%; feeding difficulties 66.3%; tube feeds 25.5%. (sheppard2021expandingthegenotypic pages 3-4, sheppard2021expandingthegenotypic pages 11-13) - Gastrointestinal: constipation 63.8%. (sheppard2021expandingthegenotypic pages 3-4) - Growth: short stature 57.8%. (sheppard2021expandingthegenotypic pages 3-4) - Hair/skin: hypertrichosis cubiti 57%; additional hypertrichosis patterns summarized visually in cohort figures. (sheppard2021expandingthegenotypic pages 3-4, sheppard2021expandingthegenotypic media eacdfc98) - Skeletal: vertebral anomalies 46.9%; scoliosis 21.3%. (sheppard2021expandingthegenotypic pages 3-4, sheppard2021expandingthegenotypic pages 11-13) - Cardiac: cardiac abnormalities 35.8% among those evaluated. (sheppard2021expandingthegenotypic pages 6-11) - Genitourinary: GU anomalies 46.8%; renal anomalies 28.6% in cohort subset. (sheppard2021expandingthegenotypic pages 11-13) - Immunologic: in a small tested subset (n=13), abnormal immunoglobulins 53.8% and insufficient pneumococcal response 30.8%; recurrent infections 25.7% overall. (sheppard2021expandingthegenotypic pages 11-13)

Visual evidence: Cohort phenotype distributions and dysmorphism/hypertrichosis patterns are summarized in Sheppard et al. Figures 2–3. (sheppard2021expandingthegenotypic media eacdfc98, sheppard2021expandingthegenotypic media 4a2ea034)

Population-specific variability: In a Chinese cohort (n=11), short stature and developmental delay were each 90.9%; PDA 57.1%, PFO 42.9%, and abnormal corpus callosum 50% were frequent imaging findings. (lin2023novelvariantsand pages 1-2)

3.2 Neurocognitive and behavioral phenotype (recent, 2023–2024 priority)

Neuropsychological profile (2023): Most patients performed in “below average to very low” ranges for nonverbal reasoning, visuospatial skills, attention/working memory, and math; >50% had normal-range receptive vocabulary/verbal memory/word reading; nonverbal reasoning weaker than verbal reasoning (p = .005). (ng2023individualswithwiedemannsteiner pages 1-2)

Clinic-based severity distribution (2024 real-world cohort): In a specialized Epigenetics and Chromatin Clinic, among 14 WSS patients, cognitive impairment was distributed as borderline/GDD above cutoff 21.4%, mild ID 57.1%, moderate ID 21.4%. (harris2024fiveyearsof pages 7-9)

3.3 Phenotype characteristics: onset, progression, and severity

  • Onset: typically congenital/early childhood with early developmental delay and postnatal growth deficiency. (ng2023individualswithwiedemannsteiner pages 1-2, sheppard2021expandingthegenotypic pages 3-4)
  • Developmental trajectory: median age at walking 20 months and first words 18 months; ranges can extend to 60 months. (sheppard2021expandingthegenotypic pages 11-13)
  • Adulthood: adult outcomes are variable; in one cohort summary of 23 adults, most completed high school (17/18 with schooling data), few attended tertiary education (3), and employment was limited (10 unemployed). (sheppard2021expandingthegenotypic pages 11-13)

3.4 HPO term suggestions (non-exhaustive)

(Representative mappings for knowledge-base entry) - Global developmental delay — HP:0001263 - Intellectual disability — HP:0001249 - Hypotonia — HP:0001252 - Seizures — HP:0001250 - Short stature — HP:0004322 - Failure to thrive — HP:0001508 - Feeding difficulties — HP:0011968 - Constipation — HP:0002019 - Hypertrichosis cubiti — HP:0004558 (commonly used clinically for elbow hypertrichosis) - Abnormal corpus callosum morphology — HP:0001273 - Patent ductus arteriosus — HP:0001643 - Patent foramen ovale — HP:0001655 - Scoliosis — HP:0002650 - Strabismus — HP:0000486

(HPO codes are standard; specific HPO coding was not enumerated in the retrieved text and is provided as ontology mapping consistent with phenotype names.)

4. Genetic / Molecular Information

4.1 Causal gene

  • KMT2A (lysine methyltransferase 2A; histone H3K4 methyltransferase; epigenetic “writer”). (foroutan2022clinicalutilityof pages 2-3, ng2023individualswithwiedemannsteiner pages 1-2)

4.2 Pathogenic variant classes and frequencies

Largest cohort variant spectrum (n=104; 82 distinct variants): - Frameshift 37.8% - Nonsense 29.3% - Missense 20.7% - Splice-site 11% - Most variants detected by exome sequencing; 80/82 absent from gnomAD v2.1.1. (sheppard2021expandingthegenotypic pages 4-6)

Genotype–phenotype correlations: hypotonia associated with loss-of-function variants; seizures associated with non-loss-of-function variants. (sheppard2021expandingthegenotypic pages 3-4)

4.3 Variant interpretation challenges and epigenetic functional testing

Variant classification can be difficult for rare missense/VUS in KMT2A; a genome-wide DNA methylation episignature has been proposed/used as a functional biomarker to classify VUS and confirm diagnoses. (foroutan2022clinicalutilityof pages 2-3)

Independent validation (2024): Husson et al. reported that their leave-one-out episignature approach achieved 100% specificity overall but that signatures vary widely; the KMT2A episignature reached “70–100% sensitivity at best with unstable performances,” suggesting it can be useful but requires cautious interpretation and larger validation datasets. (husson2024episignaturesinpractice pages 1-2)

5. Environmental Information

No specific environmental contributors, lifestyle factors, or infectious triggers for disease onset are supported by the retrieved evidence; WSS is primarily a genetic haploinsufficiency syndrome.

6. Mechanism / Pathophysiology

6.1 Epigenetic/transcriptional dysregulation (upstream mechanism)

KMT2A encodes an H3K4 methyltransferase essential for development; pathogenic variants cause chromatin remodeling defects and dysregulated gene expression. (foroutan2022clinicalutilityof pages 2-3, yu2022wiedemann–steinersyndromecase pages 1-2)

Methylation biomarker insight: Foroutan et al. reported that the methylation changes “involve global reduction in methylation in various genes, including homeobox gene promoters,” supporting developmental transcriptional dysregulation as a unifying mechanism for pleiotropy. (foroutan2022clinicalutilityof pages 2-3)

6.2 Centrosome and microtubule nucleation dysfunction (2024 mechanistic advance)

A major recent mechanistic development is the demonstration that KMT2A/MLL1 has a centrosomal function via WDR5 and Cep72: - The MLL/KMT2A–WDR5 complex localizes to pericentriolar material and interacts with Cep72 and γ-TuRC components. - Loss of MLL/WDR5 impairs microtubule nucleation/regrowth and disrupts spindle formation. - Importantly, similar defects were observed in patient-derived cells from WSS individuals (reduced centrosomal localization of AKAP9, NEDD1, γ-tubulin, and Cep72, with impaired microtubule nucleation), providing disease-relevant cellular pathophysiology. (chodisetty2024mllwdr5complexrecruits pages 1-2, chodisetty2024mllwdr5complexrecruits pages 13-14)

6.3 Transcriptomic profiling in patient-derived fibroblasts

RNA-seq of fibroblasts from 4 WSS patients (vs 5 controls) identified 1,181 DEGs (p<0.05) and 188 DEGs (p<0.01; fold change>2) with predominance of downregulation; pathway analysis highlighted eNOS signaling and axonal guidance among enriched pathways, linking KMT2A loss to neurodevelopmental and hair-growth pathways. (mietton2018rnasequencingand pages 4-5)

6.4 Model organism evidence (translational mechanisms)

Mouse models demonstrate neurobehavioral and neuronal-structure phenotypes consistent with WSS biology: - Kmt2a haploinsufficiency and Kdm5c deficiency share reduced dendritic spines and increased aggression; double mutants partially rescue dendritic morphology, behavior, transcriptomes, and H3K4me landscapes—supporting the concept that balancing writer/eraser activity can ameliorate phenotypes in principle. (vallianatos2020mutuallysuppressiveroles pages 1-2)

6.5 Suggested ontology terms

GO Biological Process (examples): - Histone H3-K4 methylation — GO:0051568 - Chromatin organization — GO:0006325 - Regulation of transcription, DNA-templated — GO:0006355 - Microtubule nucleation — GO:0007020 - Mitotic spindle organization — GO:0007052

Cell types (CL examples; context-dependent): - Neuron — CL:0000540 - Neural progenitor cell — CL:0000047 - B cell (patient-derived lymphocytes used in mechanism study) — CL:0000236

Anatomy (UBERON examples): - Brain — UBERON:0000955 - Cerebral cortex — UBERON:0001851 - Pituitary gland — UBERON:0000007

(These ontology IDs are standard mappings of terms used in studies; the retrieved texts did not enumerate ontology IDs explicitly.)

7. Anatomical Structures Affected

Based on phenotype distributions and mechanistic studies, WSS primarily affects: - Central nervous system/brain (neurodevelopmental delay, structural brain abnormalities such as corpus callosum anomalies) (sheppard2021expandingthegenotypic pages 6-11, lin2023novelvariantsand pages 1-2) - Endocrine/growth axis (short stature, GH deficiency, pituitary MRI abnormalities in subset) (sheppard2021expandingthegenotypic pages 11-13) - Cardiovascular system (cardiac anomalies; PDA/PFO in some cohorts) (sheppard2021expandingthegenotypic pages 6-11, lin2023novelvariantsand pages 1-2) - GI system (feeding difficulties, constipation) (sheppard2021expandingthegenotypic pages 3-4) - Musculoskeletal system (vertebral anomalies, scoliosis) (sheppard2021expandingthegenotypic pages 3-4, sheppard2021expandingthegenotypic pages 11-13) - Integument/hair (hypertrichosis patterns) (sheppard2021expandingthegenotypic media eacdfc98)

Subcellular localization/mechanisms implicated include nuclear chromatin regulation and centrosome/pericentriolar material functions. (foroutan2022clinicalutilityof pages 2-3, chodisetty2024mllwdr5complexrecruits pages 1-2)

8. Temporal Development

  • Typical onset: congenital/infancy with developmental delay and growth deficiency. (sheppard2021expandingthegenotypic pages 3-4)
  • Course: chronic/lifelong neurodevelopmental disorder with variable severity; adults show variable independence and employment outcomes. (sheppard2021expandingthegenotypic pages 11-13)

9. Inheritance and Population

9.1 Inheritance

  • Autosomal dominant with predominantly de novo pathogenic variants. (ng2023individualswithwiedemannsteiner pages 1-2, sheppard2021expandingthegenotypic pages 6-11)
  • Familial transmission and mosaicism reported in a minority. (baer2018wiedemann‐steinersyndromeas pages 1-2, ng2023individualswithwiedemannsteiner pages 1-2)

9.2 Epidemiology

Published estimates vary across sources: - Lin et al. (2023) state prevalence <1/1,000,000 and <400 reported cases worldwide (reflecting underdiagnosis and earlier ascertainment). (lin2023novelvariantsand pages 2-3) - Yu et al. (2022 review) reports a revised estimate from 1/100,000 to ~1/25,000–40,000 with increasing identification through sequencing. (yu2022wiedemann–steinersyndromecase pages 1-2)

These discrepancies likely reflect ascertainment differences and evolving molecular diagnosis; robust population prevalence remains uncertain in the retrieved evidence.

10. Diagnostics

10.1 Genetic testing (current practice)

  • Exome sequencing (WES) is heavily utilized in cohorts and case reports and captures diverse variant classes; in one Korean cohort, 9/10 were diagnosed by exome sequencing, with one microdeletion detected by chromosomal microarray. (lin2023novelvariantsand pages 2-3)
  • Copy-number testing (CMA/qPCR/MLPA as appropriate) is needed for intragenic/multi-exon deletions and 11q23.3 deletions encompassing KMT2A; Chinese cohort used qPCR to assess multi-exon deletions. (lin2023novelvariantsand pages 2-3)

10.2 DNA methylation episignature testing (2023–2024 development)

  • A KMT2A-related DNA methylation episignature has been proposed as a molecular biomarker to confirm diagnosis and classify VUS. (foroutan2022clinicalutilityof pages 2-3)
  • Independent evaluation emphasizes high specificity but variable sensitivity; for KMT2A “70–100% sensitivity at best with unstable performances.” (husson2024episignaturesinpractice pages 1-2)

10.3 Differential diagnosis

WSS overlaps with other chromatinopathies (e.g., Kabuki syndrome [KMT2D], Rubinstein–Taybi, Coffin–Siris, Kleefstra), complicating phenotype-only diagnosis. (vallianatos2020mutuallysuppressiveroles pages 1-2, foroutan2022clinicalutilityof pages 2-3)

11. Outcome / Prognosis

  • Survival/life expectancy: not quantified in retrieved evidence; no cohort-based mortality estimates available here.
  • Functional outcomes: variable; in the adult subset of the 104-person cohort, most completed high school but many required special education; tertiary education was uncommon and employment limited (10/23 adults unemployed). (sheppard2021expandingthegenotypic pages 11-13)
  • Complications: multi-system involvement is common (cardiac, endocrine, immunologic), supporting multidisciplinary surveillance. (sheppard2021expandingthegenotypic pages 11-13, sheppard2021expandingthegenotypic pages 6-11)

12. Treatment

12.1 Current standard of care (symptomatic/supportive)

WSS management is typically multidisciplinary and symptom-directed: - Developmental interventions: early intervention, PT/OT/speech therapy; PT case study supports early PT from infancy and goal-based functional outcome tracking. (mendoza2020physicaltherapymanagement pages 1-2) - Feeding/nutrition: management of feeding difficulties and tube feeding when necessary (25.5% in one cohort). (sheppard2021expandingthegenotypic pages 11-13) - Neurobehavioral care: educational supports, neuropsychological evaluation, ADHD/anxiety management as indicated; cognitive profile studies support targeted accommodations. (ng2023individualswithwiedemannsteiner pages 1-2, harris2024fiveyearsof pages 5-7) - System surveillance: cardiac evaluation, neuroimaging when indicated, endocrine evaluation for growth/pubertal abnormalities, and immune workup in those with recurrent infections. (baer2018wiedemann‐steinersyndromeas pages 10-11, sheppard2021expandingthegenotypic pages 11-13)

12.2 Recombinant human growth hormone (rhGH) for short stature / GH deficiency

Evidence is largely from case series and observational cohorts: - In Sheppard et al., GH deficiency was noted in 18.8% of an endocrine-evaluated subset; GH therapy was given to 3 and recommended to 3 more. (sheppard2021expandingthegenotypic pages 11-13) - A 2023 case report documented provocation peak GH 6.9 ng/mL and improvement of height to the 10th percentile after 1 year of rhGH. (kim2023growthhormonedeficiency pages 1-2)

(Additional rhGH quantitative outcomes exist in 2025 literature retrieved but post-date the requested 2023–2024 prioritization; they are not required to establish current practice trends.) (wang2025diagnosisandrecombinant pages 1-2)

12.3 Experimental / targeted therapeutics

No clinical trials were identified for treating WSS neurodevelopmental features directly in the retrieved evidence. The clinical trials retrieved for “KMT2A” primarily target KMT2A-rearranged leukemias and are not applicable to WSS.

12.4 MAXO term suggestions (examples)

  • Recombinant human growth hormone therapy — MAXO:0000600 (growth hormone therapy)
  • Physical therapy — MAXO:0000011
  • Occupational therapy — MAXO:0000012
  • Speech therapy — MAXO:0000026
  • Genetic counseling — MAXO:0000079

(MAXO codes are provided as standard mappings; not enumerated in retrieved text.)

13. Prevention

Primary prevention of de novo WSS is not established. Standard approaches include: - Genetic counseling regarding recurrence risk (generally low for de novo variants but higher with parental mosaicism). Mosaicism has been documented, supporting discussion of recurrence possibilities. (baer2018wiedemann‐steinersyndromeas pages 1-2, ng2023individualswithwiedemannsteiner pages 1-2) - Prenatal/preimplantation testing is feasible when a familial pathogenic variant is known (not directly evidenced in retrieved texts).

14. Other Species / Natural Disease

No naturally occurring veterinary WSS analogs were identified in retrieved evidence.

15. Model Organisms

  • Mouse models: Kmt2a haploinsufficient mice model aspects of WSS neurobiology, with behavioral and dendritic spine phenotypes; interaction with Kdm5c suggests potential compensatory mechanisms via epigenetic balance. (vallianatos2020mutuallysuppressiveroles pages 1-2, vallianatos2020mutuallysuppressiveroles pages 2-3)
  • Cell models: patient-derived B lymphocytes show centrosome/microtubule nucleation defects consistent with KMT2A/MLL1–WDR5 mechanism. (chodisetty2024mllwdr5complexrecruits pages 13-14, chodisetty2024mllwdr5complexrecruits pages 1-2)
  • Patient-derived fibroblasts: transcriptomic dysregulation and pathway enrichment (eNOS signaling, axonal guidance) with targeted H3K4me3 profiling. (mietton2018rnasequencingand pages 4-5)

Recent developments (2023–2024) — Highlights

  1. Neurocognitive profiling (2023): evidence for a syndrome-specific cognitive pattern emphasizing nonverbal/visuospatial weaknesses and relative verbal sparing, enabling targeted educational interventions. (ng2023individualswithwiedemannsteiner pages 1-2)
  2. Clinical adoption of episignatures (2024): independent validation underscores the promise and limitations of KMT2A episignature testing (high specificity; variable/unstable sensitivity), supporting cautious implementation in molecular diagnostics. (husson2024episignaturesinpractice pages 1-2)
  3. Mechanistic advance (2024): discovery of centrosomal role of KMT2A/MLL1–WDR5 with patient-cell phenocopy provides a new cellular disease axis beyond transcriptional regulation alone. (chodisetty2024mllwdr5complexrecruits pages 1-2)

Summary Table (curated)

The following artifact consolidates key quantitative findings (phenotype frequencies, milestones, variant spectrum) from the highest-yield cohort and supporting studies.

Domain Feature/Statistic Value Study/Population Notes
Clinical features Developmental delay and/or intellectual disability 97% Sheppard et al. 2021, multicenter cohort (n=104) (sheppard2021expandingthegenotypic pages 3-4) Core neurodevelopmental feature in the largest cohort
Clinical features Failure to thrive 67.7% Sheppard et al. 2021, multicenter cohort (n=104) (sheppard2021expandingthegenotypic pages 3-4) Common early growth problem
Clinical features Feeding difficulties 66.3% Sheppard et al. 2021, multicenter cohort (n=104) (sheppard2021expandingthegenotypic pages 3-4) Tube feeds reported in 25.5% in extended cohort summary (sheppard2021expandingthegenotypic pages 11-13)
Clinical features Constipation 63.8% Sheppard et al. 2021, multicenter cohort (n=104) (sheppard2021expandingthegenotypic pages 3-4) Frequent gastrointestinal comorbidity
Clinical features Short stature 57.8% Sheppard et al. 2021, multicenter cohort (n=104) (sheppard2021expandingthegenotypic pages 3-4) Postnatal growth deficiency is a hallmark finding
Clinical features Hypertrichosis cubiti 57.0% Sheppard et al. 2021, multicenter cohort (n=104) (sheppard2021expandingthegenotypic pages 3-4) Historically considered highly suggestive, but not universal
Clinical features Vertebral anomalies 46.9% Sheppard et al. 2021, multicenter cohort (n=104) (sheppard2021expandingthegenotypic pages 3-4) Supports skeletal surveillance
Clinical features Hypotonia 72.4% Sheppard et al. 2021, multicenter cohort (n=104) (sheppard2021expandingthegenotypic pages 6-11) Later associated with LoF variants in cohort analysis
Clinical features Hyperactivity 44.3% Sheppard et al. 2021, multicenter cohort (n=104) (sheppard2021expandingthegenotypic pages 6-11) Behavioral/psychiatric burden is substantial
Clinical features Aggressive behavior 33.0% Sheppard et al. 2021, multicenter cohort (n=104) (sheppard2021expandingthegenotypic pages 6-11) Behavioral support often needed
Clinical features Autism spectrum disorder 21.3% Sheppard et al. 2021, multicenter cohort (n=104) (sheppard2021expandingthegenotypic pages 6-11) Not universal but clinically relevant
Clinical features Seizures 20.0% Sheppard et al. 2021, surveyed subset of cohort (sheppard2021expandingthegenotypic pages 6-11) Reported association with non-LoF variants
Clinical features Structural brain abnormality on imaging 57.5% Sheppard et al. 2021, imaged subgroup (n=52) (sheppard2021expandingthegenotypic pages 6-11) Includes corpus callosum and myelination abnormalities
Clinical features Cardiac abnormalities 35.8% Sheppard et al. 2021, evaluated subgroup (29/81) (sheppard2021expandingthegenotypic pages 6-11) Structural anomalies also emphasized in review literature
Clinical features Genitourinary anomalies 46.8% Sheppard et al. 2021, multicenter cohort (n=104) (sheppard2021expandingthegenotypic pages 11-13) Renal anomaly 28.6%; uterine/testicular anomalies 16.9%
Clinical features Recurrent infections 25.7% Sheppard et al. 2021, multicenter cohort (n=104) (sheppard2021expandingthegenotypic pages 11-13) Supports consideration of immune evaluation
Clinical features Abnormal immunoglobulins 53.8% Sheppard et al. 2021, tested subgroup (n=13) (sheppard2021expandingthegenotypic pages 11-13) Small tested subset only
Developmental milestones Sitting independently Median 10 months (range 6-36) Sheppard et al. 2021, multicenter cohort (sheppard2021expandingthegenotypic pages 11-13) Delayed relative to typical development
Developmental milestones Standing independently Median 17 months (range 8-60) Sheppard et al. 2021, multicenter cohort (sheppard2021expandingthegenotypic pages 11-13) Marked gross motor delay
Developmental milestones Walking independently Median 20 months (range 11-60) Sheppard et al. 2021, multicenter cohort (sheppard2021expandingthegenotypic pages 3-4, sheppard2021expandingthegenotypic pages 11-13) Frequently cited milestone delay in WSS
Developmental milestones First words Median 18 months (range 8-60) Sheppard et al. 2021, multicenter cohort (sheppard2021expandingthegenotypic pages 3-4, sheppard2021expandingthegenotypic pages 11-13) Language delay common but variable
Clinical features Short stature 90.9% Lin et al. 2023, Chinese cohort (n=11) (lin2023novelvariantsand pages 1-2, lin2023novelvariantsand pages 2-3) Higher than in Sheppard cohort
Clinical features Developmental delay 90.9% Lin et al. 2023, Chinese cohort (n=11) (lin2023novelvariantsand pages 1-2, lin2023novelvariantsand pages 2-3) Confirms high frequency across populations
Clinical features Intellectual disability 72.7% Lin et al. 2023, Chinese cohort (n=11) (lin2023novelvariantsand pages 1-2, lin2023novelvariantsand pages 2-3) Smaller cohort, likely ascertainment effects
Clinical features Patent ductus arteriosus 57.1% Lin et al. 2023, Chinese cohort imaging findings (lin2023novelvariantsand pages 1-2) Frequent cardiovascular imaging finding in this cohort
Clinical features Patent foramen ovale 42.9% Lin et al. 2023, Chinese cohort imaging findings (lin2023novelvariantsand pages 1-2) Common but potentially incidental in some children
Clinical features Abnormal corpus callosum 50.0% Lin et al. 2023, Chinese cohort imaging findings (lin2023novelvariantsand pages 1-2) Supports neuroimaging when clinically indicated
Clinical features Developmental delay 84.6% Lin et al. 2023, combined Chinese cases (n=52) (lin2023novelvariantsand pages 1-2) Review-level estimate across reported Chinese patients
Clinical features Intellectual disability 84.6% Lin et al. 2023, combined Chinese cases (n=52) (lin2023novelvariantsand pages 1-2) Similar to developmental delay frequency
Clinical features Short stature 80.8% Lin et al. 2023, combined Chinese cases (n=52) (lin2023novelvariantsand pages 1-2) Suggests growth phenotype may be prominent in Chinese reports
Clinical features Delayed bone age 68.0% Lin et al. 2023, combined Chinese cases (n=52) (lin2023novelvariantsand pages 1-2) Bone age may be delayed or, in other reports, advanced
Variant spectrum Distinct KMT2A variants identified 82 Sheppard et al. 2021, multicenter cohort (n=104) (sheppard2021expandingthegenotypic pages 3-4, sheppard2021expandingthegenotypic pages 4-6) 69/82 were novel
Variant spectrum Novel variants among distinct variants 84% (69/82) Sheppard et al. 2021, multicenter cohort (sheppard2021expandingthegenotypic pages 3-4, sheppard2021expandingthegenotypic pages 4-6) Highlights allelic heterogeneity
Variant spectrum De novo variants 55.8% Sheppard et al. 2021, cohort summary (sheppard2021expandingthegenotypic pages 6-11) Likely underestimate due to incomplete parental testing
Variant spectrum Frameshift variants 37.8% Sheppard et al. 2021, variant spectrum (sheppard2021expandingthegenotypic pages 4-6) Largest variant class in this cohort
Variant spectrum Nonsense variants 29.3% Sheppard et al. 2021, variant spectrum (sheppard2021expandingthegenotypic pages 4-6) Supports haploinsufficiency mechanism
Variant spectrum Missense variants 20.7% Sheppard et al. 2021, variant spectrum (sheppard2021expandingthegenotypic pages 4-6) Missense variants often cluster in functional domains
Variant spectrum Splice-site variants 11.0% Sheppard et al. 2021, variant spectrum (sheppard2021expandingthegenotypic pages 4-6) Rounded from reported 11%
Variant spectrum Variants absent from gnomAD v2.1.1 80/82 Sheppard et al. 2021, variant spectrum (sheppard2021expandingthegenotypic pages 4-6) Consistent with rarity and pathogenic enrichment
Variant spectrum Variants identified 11 total (3 known, 8 novel) Lin et al. 2023, Chinese cohort (n=11) (lin2023novelvariantsand pages 1-2) No hotspot variant detected
Variant spectrum HGMD-listed KMT2A variants 349 total Lin et al. 2023 background summary (lin2023novelvariantsand pages 1-2) 273 disease-causing, 76 possible disease-causing
Variant spectrum Reported KMT2A variants in review 322 Yu et al. 2022 review (yu2022wiedemann–steinersyndromecase pages 7-8) Included missense, nonsense, frameshift, and splicing variants
Variant spectrum Variants in exons 3 and 27 >50% of pathogenic variants Yu et al. 2022 review (yu2022wiedemann–steinersyndromecase pages 7-8) Review-level observation, not cohort-specific
Treatment/management rhGH-treated patients with satisfactory height gain 2/2 Lin et al. 2023, Chinese cohort (lin2023novelvariantsand pages 1-2) One patient developed accelerated bone age
Treatment/management Growth hormone deficiency 18.8% Sheppard et al. 2021, endocrine subgroup (sheppard2021expandingthegenotypic pages 11-13) Supports endocrine assessment in selected patients
Treatment/management Growth hormone deficiency 18.8%-50% Yu et al. 2022 review (yu2022wiedemann–steinersyndromecase pages 7-8) Range reflects literature variability
Epidemiology Estimated prevalence <1/1,000,000 Lin et al. 2023 background summary (lin2023novelvariantsand pages 2-3) Authors also noted <400 reported cases worldwide at that time
Epidemiology Revised prevalence estimate ~1 in 25,000-40,000 Yu et al. 2022 review (yu2022wiedemann–steinersyndromecase pages 1-2) Review noted ascertainment likely increased with sequencing

Table: This table compiles key quantitative findings for Wiedemann–Steiner syndrome across major cohort and review papers, emphasizing phenotype frequencies, developmental milestones, and KMT2A variant spectrum statistics. It is useful as a quick-reference evidence summary for clinical and knowledge-base curation.

Key URLs and publication dates (from retrieved evidence)

  • Sheppard et al., Am J Med Genet A (2021-03): https://doi.org/10.1002/ajmg.a.62124 (sheppard2021expandingthegenotypic pages 3-4)
  • Lin et al., Front Genet (2023-03): https://doi.org/10.3389/fgene.2023.1085210 (lin2023novelvariantsand pages 1-2)
  • Ng et al., J Int Neuropsychol Soc (2023-09): https://doi.org/10.1017/S1355617722000467 (ng2023individualswithwiedemannsteiner pages 1-2)
  • Husson et al., Eur J Hum Genet (2024-10): https://doi.org/10.1038/s41431-023-01474-x (husson2024episignaturesinpractice pages 1-2)
  • Harris et al., Human Genetics (2024-03): https://doi.org/10.1007/s00439-023-02537-1 (harris2024fiveyearsof pages 7-9)
  • Chodisetty et al., Science Advances (2024-12): https://doi.org/10.1126/sciadv.adn0086 (chodisetty2024mllwdr5complexrecruits pages 1-2)
  • Foroutan et al., Int J Mol Sci (2022-02): https://doi.org/10.3390/ijms23031815 (foroutan2022clinicalutilityof pages 2-3)
  • Mietton et al., NeuroMolecular Medicine (2018-07): https://doi.org/10.1007/s12017-018-8502-1 (mietton2018rnasequencingand pages 4-5)

Limitations of this tool-based report

  • Not all requested identifiers (Orphanet, ICD-10/ICD-11, MeSH) were retrievable with the available tool evidence; they should be added from OMIM/Orphanet/WHO ICD resources.
  • Some “expert opinions” (e.g., consensus guidelines, GeneReviews) were not obtained in the current retrieval set.
  • Prevalence estimates vary substantially across sources; robust population epidemiology remains uncertain in the retrieved evidence set. (lin2023novelvariantsand pages 2-3, yu2022wiedemann–steinersyndromecase pages 1-2)

References

  1. (sheppard2021expandingthegenotypic pages 3-4): Sarah E. Sheppard, Ian M. Campbell, Margaret H. Harr, Nina Gold, Dong Li, Hans T. Bjornsson, Julie S. Cohen, Jill A. Fahrner, Ali Fatemi, Jacqueline R. Harris, Catherine Nowak, Cathy A. Stevens, Katheryn Grand, Margaret Au, John M. Graham, Pedro A. Sanchez‐Lara, Miguel Del Campo, Marilyn C. Jones, Omar Abdul‐Rahman, Fowzan S. Alkuraya, Jennifer A. Bassetti, Katherine Bergstrom, Elizabeth Bhoj, Sarah Dugan, Julie D. Kaplan, Nada Derar, Karen W. Gripp, Natalie Hauser, A. Micheil Innes, Beth Keena, Neslida Kodra, Rebecca Miller, Beverly Nelson, Malgorzata J. Nowaczyk, Zuhair Rahbeeni, Shay Ben‐Shachar, Joseph T. Shieh, Anne Slavotinek, Andrew K. Sobering, Mary‐Alice Abbott, Dawn C. Allain, Louise Amlie‐Wolf, Ping Yee Billie Au, Emma Bedoukian, Geoffrey Beek, James Barry, Janet Berg, Jonathan A. Bernstein, Cheryl Cytrynbaum, Brian Hon‐Yin Chung, Sarah Donoghue, Naghmeh Dorrani, Alison Eaton, Josue A. Flores‐Daboub, Holly Dubbs, Carolyn A. Felix, Chin‐To Fong, Jasmine Lee Fong Fung, Balram Gangaram, Amy Goldstein, Rotem Greenberg, Thoa K. Ha, Joseph Hersh, Kosuke Izumi, Staci Kallish, Elijah Kravets, Pui‐Yan Kwok, Rebekah K. Jobling, Amy E. Knight Johnson, Jessica Kushner, Bo Hoon Lee, Brooke Levin, Kristin Lindstrom, Kandamurugu Manickam, Rebecca Mardach, Elizabeth McCormick, D. Ross McLeod, Frank D. Mentch, Kelly Minks, Colleen Muraresku, Stanley F. Nelson, Patrizia Porazzi, Pavel N. Pichurin, Nina N. Powell‐Hamilton, Zoe Powis, Alyssa Ritter, Caleb Rogers, Luis Rohena, Carey Ronspies, Audrey Schroeder, Zornitza Stark, Lois Starr, Joan Stoler, Pim Suwannarat, Milen Velinov, Rosanna Weksberg, Yael Wilnai, Neda Zadeh, Dina J. Zand, Marni J. Falk, Hakon Hakonarson, Elaine H. Zackai, and Fabiola Quintero‐Rivera. Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with wiedemann‐steiner syndrome. American Journal of Medical Genetics Part A, 185:1649-1665, Mar 2021. URL: https://doi.org/10.1002/ajmg.a.62124, doi:10.1002/ajmg.a.62124. This article has 79 citations.

  2. (sheppard2021expandingthegenotypic pages 11-13): Sarah E. Sheppard, Ian M. Campbell, Margaret H. Harr, Nina Gold, Dong Li, Hans T. Bjornsson, Julie S. Cohen, Jill A. Fahrner, Ali Fatemi, Jacqueline R. Harris, Catherine Nowak, Cathy A. Stevens, Katheryn Grand, Margaret Au, John M. Graham, Pedro A. Sanchez‐Lara, Miguel Del Campo, Marilyn C. Jones, Omar Abdul‐Rahman, Fowzan S. Alkuraya, Jennifer A. Bassetti, Katherine Bergstrom, Elizabeth Bhoj, Sarah Dugan, Julie D. Kaplan, Nada Derar, Karen W. Gripp, Natalie Hauser, A. Micheil Innes, Beth Keena, Neslida Kodra, Rebecca Miller, Beverly Nelson, Malgorzata J. Nowaczyk, Zuhair Rahbeeni, Shay Ben‐Shachar, Joseph T. Shieh, Anne Slavotinek, Andrew K. Sobering, Mary‐Alice Abbott, Dawn C. Allain, Louise Amlie‐Wolf, Ping Yee Billie Au, Emma Bedoukian, Geoffrey Beek, James Barry, Janet Berg, Jonathan A. Bernstein, Cheryl Cytrynbaum, Brian Hon‐Yin Chung, Sarah Donoghue, Naghmeh Dorrani, Alison Eaton, Josue A. Flores‐Daboub, Holly Dubbs, Carolyn A. Felix, Chin‐To Fong, Jasmine Lee Fong Fung, Balram Gangaram, Amy Goldstein, Rotem Greenberg, Thoa K. Ha, Joseph Hersh, Kosuke Izumi, Staci Kallish, Elijah Kravets, Pui‐Yan Kwok, Rebekah K. Jobling, Amy E. Knight Johnson, Jessica Kushner, Bo Hoon Lee, Brooke Levin, Kristin Lindstrom, Kandamurugu Manickam, Rebecca Mardach, Elizabeth McCormick, D. Ross McLeod, Frank D. Mentch, Kelly Minks, Colleen Muraresku, Stanley F. Nelson, Patrizia Porazzi, Pavel N. Pichurin, Nina N. Powell‐Hamilton, Zoe Powis, Alyssa Ritter, Caleb Rogers, Luis Rohena, Carey Ronspies, Audrey Schroeder, Zornitza Stark, Lois Starr, Joan Stoler, Pim Suwannarat, Milen Velinov, Rosanna Weksberg, Yael Wilnai, Neda Zadeh, Dina J. Zand, Marni J. Falk, Hakon Hakonarson, Elaine H. Zackai, and Fabiola Quintero‐Rivera. Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with wiedemann‐steiner syndrome. American Journal of Medical Genetics Part A, 185:1649-1665, Mar 2021. URL: https://doi.org/10.1002/ajmg.a.62124, doi:10.1002/ajmg.a.62124. This article has 79 citations.

  3. (sheppard2021expandingthegenotypic pages 6-11): Sarah E. Sheppard, Ian M. Campbell, Margaret H. Harr, Nina Gold, Dong Li, Hans T. Bjornsson, Julie S. Cohen, Jill A. Fahrner, Ali Fatemi, Jacqueline R. Harris, Catherine Nowak, Cathy A. Stevens, Katheryn Grand, Margaret Au, John M. Graham, Pedro A. Sanchez‐Lara, Miguel Del Campo, Marilyn C. Jones, Omar Abdul‐Rahman, Fowzan S. Alkuraya, Jennifer A. Bassetti, Katherine Bergstrom, Elizabeth Bhoj, Sarah Dugan, Julie D. Kaplan, Nada Derar, Karen W. Gripp, Natalie Hauser, A. Micheil Innes, Beth Keena, Neslida Kodra, Rebecca Miller, Beverly Nelson, Malgorzata J. Nowaczyk, Zuhair Rahbeeni, Shay Ben‐Shachar, Joseph T. Shieh, Anne Slavotinek, Andrew K. Sobering, Mary‐Alice Abbott, Dawn C. Allain, Louise Amlie‐Wolf, Ping Yee Billie Au, Emma Bedoukian, Geoffrey Beek, James Barry, Janet Berg, Jonathan A. Bernstein, Cheryl Cytrynbaum, Brian Hon‐Yin Chung, Sarah Donoghue, Naghmeh Dorrani, Alison Eaton, Josue A. Flores‐Daboub, Holly Dubbs, Carolyn A. Felix, Chin‐To Fong, Jasmine Lee Fong Fung, Balram Gangaram, Amy Goldstein, Rotem Greenberg, Thoa K. Ha, Joseph Hersh, Kosuke Izumi, Staci Kallish, Elijah Kravets, Pui‐Yan Kwok, Rebekah K. Jobling, Amy E. Knight Johnson, Jessica Kushner, Bo Hoon Lee, Brooke Levin, Kristin Lindstrom, Kandamurugu Manickam, Rebecca Mardach, Elizabeth McCormick, D. Ross McLeod, Frank D. Mentch, Kelly Minks, Colleen Muraresku, Stanley F. Nelson, Patrizia Porazzi, Pavel N. Pichurin, Nina N. Powell‐Hamilton, Zoe Powis, Alyssa Ritter, Caleb Rogers, Luis Rohena, Carey Ronspies, Audrey Schroeder, Zornitza Stark, Lois Starr, Joan Stoler, Pim Suwannarat, Milen Velinov, Rosanna Weksberg, Yael Wilnai, Neda Zadeh, Dina J. Zand, Marni J. Falk, Hakon Hakonarson, Elaine H. Zackai, and Fabiola Quintero‐Rivera. Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with wiedemann‐steiner syndrome. American Journal of Medical Genetics Part A, 185:1649-1665, Mar 2021. URL: https://doi.org/10.1002/ajmg.a.62124, doi:10.1002/ajmg.a.62124. This article has 79 citations.

  4. (ng2023individualswithwiedemannsteiner pages 1-2): Rowena Ng, Jacqueline Harris, Jill A. Fahrner, and Hans Tomas Bjornsson. Individuals with wiedemann-steiner syndrome show nonverbal reasoning and visuospatial defects with relative verbal skill sparing. Journal of the International Neuropsychological Society, 29:512-518, Sep 2023. URL: https://doi.org/10.1017/s1355617722000467, doi:10.1017/s1355617722000467. This article has 16 citations and is from a domain leading peer-reviewed journal.

  5. (foroutan2022clinicalutilityof pages 2-3): Aidin Foroutan, Sadegheh Haghshenas, Pratibha Bhai, Michael A. Levy, Jennifer Kerkhof, Haley McConkey, Marcello Niceta, Andrea Ciolfi, Lucia Pedace, Evelina Miele, David Genevieve, Solveig Heide, Mariëlle Alders, Giuseppe Zampino, Giuseppe Merla, Mélanie Fradin, Eric Bieth, Dominique Bonneau, Klaus Dieterich, Patricia Fergelot, Elise Schaefer, Laurence Faivre, Antonio Vitobello, Silvia Maitz, Rita Fischetto, Cristina Gervasini, Maria Piccione, Ingrid van de Laar, Marco Tartaglia, Bekim Sadikovic, and Anne-Sophie Lebre. Clinical utility of a unique genome-wide dna methylation signature for kmt2a-related syndrome. International Journal of Molecular Sciences, 23:1815, Feb 2022. URL: https://doi.org/10.3390/ijms23031815, doi:10.3390/ijms23031815. This article has 23 citations.

  6. (OpenTargets Search: Wiedemann-Steiner syndrome-KMT2A): Open Targets Query (Wiedemann-Steiner syndrome-KMT2A, 1 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

  7. (harris2024fiveyearsof pages 7-9): Jacqueline R. Harris, Christine W. Gao, Jacquelyn F. Britton, Carolyn D. Applegate, Hans T. Bjornsson, and Jill A. Fahrner. Five years of experience in the epigenetics and chromatin clinic: what have we learned and where do we go from here? Human Genetics, 143:1-18, Mar 2024. URL: https://doi.org/10.1007/s00439-023-02537-1, doi:10.1007/s00439-023-02537-1. This article has 40 citations and is from a peer-reviewed journal.

  8. (lin2023novelvariantsand pages 2-3): Yunting Lin, Xiaohong Chen, Bobo Xie, Zhihong Guan, Xiaodan Chen, Xiuzhen Li, Peng Yi, Rong Du, Huifen Mei, Li Liu, Wen Zhang, and Chunhua Zeng. Novel variants and phenotypic heterogeneity in a cohort of 11 chinese children with wiedemann-steiner syndrome. Frontiers in Genetics, Mar 2023. URL: https://doi.org/10.3389/fgene.2023.1085210, doi:10.3389/fgene.2023.1085210. This article has 10 citations and is from a peer-reviewed journal.

  9. (yu2022wiedemann–steinersyndromecase pages 7-8): Huan Yu, Guijiao Zhang, Shengxu Yu, and Wei Wu. Wiedemann–steiner syndrome: case report and review of literature. Children, 9:1545, Oct 2022. URL: https://doi.org/10.3390/children9101545, doi:10.3390/children9101545. This article has 16 citations.

  10. (husson2024episignaturesinpractice pages 1-2): Thomas Husson, François Lecoquierre, Gaël Nicolas, Anne-Claire Richard, Alexandra Afenjar, Séverine AUDEBERT-BELLANGER, Catherine Badens, Frédéric Bilan, Varoona Bizaoui, Anne Boland, Marie-Noelle Bonnet-Dupeyron, Elise Brischoux-Boucher, Céline Bonnet, Marie Bournez, Odile Boute, Perrine Brunelle, Roseline Caumes, Perrine Charles, Nicolas Chassaing, Nicolas Chatron, Benjamin Cogné, Estelle Colin, Valérie Cormier-Daire, Rodolphe Dard, Benjamin Dauriat, Julian Delanne, Jean-François Deleuze, Florence Demurger, Anne-Sophie Denommé-Pichon, Christel Depienne, Anne Dieux Coeslier, Christèle Dubourg, Patrick Edery, salima EL CHEHADEH, Laurence Faivre, Mélanie FRADIN, Aurore Garde, David Geneviève, Brigitte Gilbert-Dussardier, Cyril Goizet, Alice Goldenberg, Evan Gouy, Anne-Marie Guerrot, Anne Guimier, Ines HARZALLAH, Delphine Héron, Bertrand Isidor, Xavier Le Guillou Horn, Boris Keren, Alma Kuechler, Elodie Lacaze, Alinoë Lavillaureix, Daphné Lehalle, Gaetan Lesca, James Lespinasse, Jonathan Levy, Stanislas Lyonnet, Godelieve Morel, Nolwenn Jean Marçais, Sandrine Marlin, Luisa Marsili, Cyril Mignot, Sophie Nambot, Mathilde Nizon, Robert Olaso, Laurent PASQUIER, Laurine Perrin, Florence Petit, Amélie Piton, Fabienne Prieur, Audrey Putoux, Marc Planes, Sylvie Odent, Chloé Quelin, Sylvia Quemener, Mélanie Rama, Marlène RIO, Massimiliano Rossi, Elise Schaefer, Sophie Rondeau, Pascale SAUGIER-VEBER, Thomas Smol, Sabine Sigaudy, Renaud TOURAINE, Frédéric Tran-Mau-Them, Aurélien Trimouille, Clémence Vanlerberghe, Valérie Vantalon, Gabriella Vera, Marie Vincent, Alban Ziegler, Olivier Guillin, Dominique Campion, and Camille Charbonnier. Episignatures in practice: independent evaluation of published episignatures for the molecular diagnostics of ten neurodevelopmental disorders. European Journal of Human Genetics, 32:190-199, Oct 2024. URL: https://doi.org/10.1038/s41431-023-01474-x, doi:10.1038/s41431-023-01474-x. This article has 38 citations and is from a domain leading peer-reviewed journal.

  11. (harris2024fiveyearsof pages 5-7): Jacqueline R. Harris, Christine W. Gao, Jacquelyn F. Britton, Carolyn D. Applegate, Hans T. Bjornsson, and Jill A. Fahrner. Five years of experience in the epigenetics and chromatin clinic: what have we learned and where do we go from here? Human Genetics, 143:1-18, Mar 2024. URL: https://doi.org/10.1007/s00439-023-02537-1, doi:10.1007/s00439-023-02537-1. This article has 40 citations and is from a peer-reviewed journal.

  12. (yu2022wiedemann–steinersyndromecase pages 1-2): Huan Yu, Guijiao Zhang, Shengxu Yu, and Wei Wu. Wiedemann–steiner syndrome: case report and review of literature. Children, 9:1545, Oct 2022. URL: https://doi.org/10.3390/children9101545, doi:10.3390/children9101545. This article has 16 citations.

  13. (sheppard2021expandingthegenotypic pages 4-6): Sarah E. Sheppard, Ian M. Campbell, Margaret H. Harr, Nina Gold, Dong Li, Hans T. Bjornsson, Julie S. Cohen, Jill A. Fahrner, Ali Fatemi, Jacqueline R. Harris, Catherine Nowak, Cathy A. Stevens, Katheryn Grand, Margaret Au, John M. Graham, Pedro A. Sanchez‐Lara, Miguel Del Campo, Marilyn C. Jones, Omar Abdul‐Rahman, Fowzan S. Alkuraya, Jennifer A. Bassetti, Katherine Bergstrom, Elizabeth Bhoj, Sarah Dugan, Julie D. Kaplan, Nada Derar, Karen W. Gripp, Natalie Hauser, A. Micheil Innes, Beth Keena, Neslida Kodra, Rebecca Miller, Beverly Nelson, Malgorzata J. Nowaczyk, Zuhair Rahbeeni, Shay Ben‐Shachar, Joseph T. Shieh, Anne Slavotinek, Andrew K. Sobering, Mary‐Alice Abbott, Dawn C. Allain, Louise Amlie‐Wolf, Ping Yee Billie Au, Emma Bedoukian, Geoffrey Beek, James Barry, Janet Berg, Jonathan A. Bernstein, Cheryl Cytrynbaum, Brian Hon‐Yin Chung, Sarah Donoghue, Naghmeh Dorrani, Alison Eaton, Josue A. Flores‐Daboub, Holly Dubbs, Carolyn A. Felix, Chin‐To Fong, Jasmine Lee Fong Fung, Balram Gangaram, Amy Goldstein, Rotem Greenberg, Thoa K. Ha, Joseph Hersh, Kosuke Izumi, Staci Kallish, Elijah Kravets, Pui‐Yan Kwok, Rebekah K. Jobling, Amy E. Knight Johnson, Jessica Kushner, Bo Hoon Lee, Brooke Levin, Kristin Lindstrom, Kandamurugu Manickam, Rebecca Mardach, Elizabeth McCormick, D. Ross McLeod, Frank D. Mentch, Kelly Minks, Colleen Muraresku, Stanley F. Nelson, Patrizia Porazzi, Pavel N. Pichurin, Nina N. Powell‐Hamilton, Zoe Powis, Alyssa Ritter, Caleb Rogers, Luis Rohena, Carey Ronspies, Audrey Schroeder, Zornitza Stark, Lois Starr, Joan Stoler, Pim Suwannarat, Milen Velinov, Rosanna Weksberg, Yael Wilnai, Neda Zadeh, Dina J. Zand, Marni J. Falk, Hakon Hakonarson, Elaine H. Zackai, and Fabiola Quintero‐Rivera. Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with wiedemann‐steiner syndrome. American Journal of Medical Genetics Part A, 185:1649-1665, Mar 2021. URL: https://doi.org/10.1002/ajmg.a.62124, doi:10.1002/ajmg.a.62124. This article has 79 citations.

  14. (baer2018wiedemann‐steinersyndromeas pages 1-2): S. Baer, A. Afenjar, T. Smol, A. Piton, B. Gérard, Y. Alembik, T. Bienvenu, G. Boursier, O. Boute, C. Colson, M.‐P. Cordier, V. Cormier‐Daire, B. Delobel, M. Doco‐Fenzy, B. Duban‐Bedu, M. Fradin, D. Geneviève, A. Goldenberg, M. Grelet, D. Haye, D. Heron, B. Isidor, B. Keren, D. Lacombe, A.‐S. Lèbre, G. Lesca, A. Masurel, M. Mathieu‐Dramard, C. Nava, L. Pasquier, A. Petit, N. Philip, J. Piard, S. Rondeau, P. Saugier‐Veber, S. Sukno, J. Thevenon, J. Van‐Gils, C. Vincent‐Delorme, M. Willems, E. Schaefer, and G. Morin. Wiedemann‐steiner syndrome as a major cause of syndromic intellectual disability: a study of 33 french cases. Clinical Genetics, 94:141-152, Jul 2018. URL: https://doi.org/10.1111/cge.13254, doi:10.1111/cge.13254. This article has 92 citations and is from a peer-reviewed journal.

  15. (sheppard2021expandingthegenotypic media eacdfc98): Sarah E. Sheppard, Ian M. Campbell, Margaret H. Harr, Nina Gold, Dong Li, Hans T. Bjornsson, Julie S. Cohen, Jill A. Fahrner, Ali Fatemi, Jacqueline R. Harris, Catherine Nowak, Cathy A. Stevens, Katheryn Grand, Margaret Au, John M. Graham, Pedro A. Sanchez‐Lara, Miguel Del Campo, Marilyn C. Jones, Omar Abdul‐Rahman, Fowzan S. Alkuraya, Jennifer A. Bassetti, Katherine Bergstrom, Elizabeth Bhoj, Sarah Dugan, Julie D. Kaplan, Nada Derar, Karen W. Gripp, Natalie Hauser, A. Micheil Innes, Beth Keena, Neslida Kodra, Rebecca Miller, Beverly Nelson, Malgorzata J. Nowaczyk, Zuhair Rahbeeni, Shay Ben‐Shachar, Joseph T. Shieh, Anne Slavotinek, Andrew K. Sobering, Mary‐Alice Abbott, Dawn C. Allain, Louise Amlie‐Wolf, Ping Yee Billie Au, Emma Bedoukian, Geoffrey Beek, James Barry, Janet Berg, Jonathan A. Bernstein, Cheryl Cytrynbaum, Brian Hon‐Yin Chung, Sarah Donoghue, Naghmeh Dorrani, Alison Eaton, Josue A. Flores‐Daboub, Holly Dubbs, Carolyn A. Felix, Chin‐To Fong, Jasmine Lee Fong Fung, Balram Gangaram, Amy Goldstein, Rotem Greenberg, Thoa K. Ha, Joseph Hersh, Kosuke Izumi, Staci Kallish, Elijah Kravets, Pui‐Yan Kwok, Rebekah K. Jobling, Amy E. Knight Johnson, Jessica Kushner, Bo Hoon Lee, Brooke Levin, Kristin Lindstrom, Kandamurugu Manickam, Rebecca Mardach, Elizabeth McCormick, D. Ross McLeod, Frank D. Mentch, Kelly Minks, Colleen Muraresku, Stanley F. Nelson, Patrizia Porazzi, Pavel N. Pichurin, Nina N. Powell‐Hamilton, Zoe Powis, Alyssa Ritter, Caleb Rogers, Luis Rohena, Carey Ronspies, Audrey Schroeder, Zornitza Stark, Lois Starr, Joan Stoler, Pim Suwannarat, Milen Velinov, Rosanna Weksberg, Yael Wilnai, Neda Zadeh, Dina J. Zand, Marni J. Falk, Hakon Hakonarson, Elaine H. Zackai, and Fabiola Quintero‐Rivera. Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with wiedemann‐steiner syndrome. American Journal of Medical Genetics Part A, 185:1649-1665, Mar 2021. URL: https://doi.org/10.1002/ajmg.a.62124, doi:10.1002/ajmg.a.62124. This article has 79 citations.

  16. (sheppard2021expandingthegenotypic media 4a2ea034): Sarah E. Sheppard, Ian M. Campbell, Margaret H. Harr, Nina Gold, Dong Li, Hans T. Bjornsson, Julie S. Cohen, Jill A. Fahrner, Ali Fatemi, Jacqueline R. Harris, Catherine Nowak, Cathy A. Stevens, Katheryn Grand, Margaret Au, John M. Graham, Pedro A. Sanchez‐Lara, Miguel Del Campo, Marilyn C. Jones, Omar Abdul‐Rahman, Fowzan S. Alkuraya, Jennifer A. Bassetti, Katherine Bergstrom, Elizabeth Bhoj, Sarah Dugan, Julie D. Kaplan, Nada Derar, Karen W. Gripp, Natalie Hauser, A. Micheil Innes, Beth Keena, Neslida Kodra, Rebecca Miller, Beverly Nelson, Malgorzata J. Nowaczyk, Zuhair Rahbeeni, Shay Ben‐Shachar, Joseph T. Shieh, Anne Slavotinek, Andrew K. Sobering, Mary‐Alice Abbott, Dawn C. Allain, Louise Amlie‐Wolf, Ping Yee Billie Au, Emma Bedoukian, Geoffrey Beek, James Barry, Janet Berg, Jonathan A. Bernstein, Cheryl Cytrynbaum, Brian Hon‐Yin Chung, Sarah Donoghue, Naghmeh Dorrani, Alison Eaton, Josue A. Flores‐Daboub, Holly Dubbs, Carolyn A. Felix, Chin‐To Fong, Jasmine Lee Fong Fung, Balram Gangaram, Amy Goldstein, Rotem Greenberg, Thoa K. Ha, Joseph Hersh, Kosuke Izumi, Staci Kallish, Elijah Kravets, Pui‐Yan Kwok, Rebekah K. Jobling, Amy E. Knight Johnson, Jessica Kushner, Bo Hoon Lee, Brooke Levin, Kristin Lindstrom, Kandamurugu Manickam, Rebecca Mardach, Elizabeth McCormick, D. Ross McLeod, Frank D. Mentch, Kelly Minks, Colleen Muraresku, Stanley F. Nelson, Patrizia Porazzi, Pavel N. Pichurin, Nina N. Powell‐Hamilton, Zoe Powis, Alyssa Ritter, Caleb Rogers, Luis Rohena, Carey Ronspies, Audrey Schroeder, Zornitza Stark, Lois Starr, Joan Stoler, Pim Suwannarat, Milen Velinov, Rosanna Weksberg, Yael Wilnai, Neda Zadeh, Dina J. Zand, Marni J. Falk, Hakon Hakonarson, Elaine H. Zackai, and Fabiola Quintero‐Rivera. Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with wiedemann‐steiner syndrome. American Journal of Medical Genetics Part A, 185:1649-1665, Mar 2021. URL: https://doi.org/10.1002/ajmg.a.62124, doi:10.1002/ajmg.a.62124. This article has 79 citations.

  17. (lin2023novelvariantsand pages 1-2): Yunting Lin, Xiaohong Chen, Bobo Xie, Zhihong Guan, Xiaodan Chen, Xiuzhen Li, Peng Yi, Rong Du, Huifen Mei, Li Liu, Wen Zhang, and Chunhua Zeng. Novel variants and phenotypic heterogeneity in a cohort of 11 chinese children with wiedemann-steiner syndrome. Frontiers in Genetics, Mar 2023. URL: https://doi.org/10.3389/fgene.2023.1085210, doi:10.3389/fgene.2023.1085210. This article has 10 citations and is from a peer-reviewed journal.

  18. (chodisetty2024mllwdr5complexrecruits pages 1-2): Swathi Chodisetty, Aditi Arora, Kausika Kumar Malik, Himanshu Goel, and Shweta Tyagi. Mll/wdr5 complex recruits centriolar satellite protein cep72 to regulate microtubule nucleation and spindle formation. Dec 2024. URL: https://doi.org/10.1126/sciadv.adn0086, doi:10.1126/sciadv.adn0086. This article has 5 citations and is from a highest quality peer-reviewed journal.

  19. (chodisetty2024mllwdr5complexrecruits pages 13-14): Swathi Chodisetty, Aditi Arora, Kausika Kumar Malik, Himanshu Goel, and Shweta Tyagi. Mll/wdr5 complex recruits centriolar satellite protein cep72 to regulate microtubule nucleation and spindle formation. Dec 2024. URL: https://doi.org/10.1126/sciadv.adn0086, doi:10.1126/sciadv.adn0086. This article has 5 citations and is from a highest quality peer-reviewed journal.

  20. (mietton2018rnasequencingand pages 4-5): Léo Mietton, Nicolas Lebrun, Irina Giurgea, Alice Goldenberg, Benjamin Saintpierre, Juliette Hamroune, Alexandra Afenjar, Pierre Billuart, and Thierry Bienvenu. Rna sequencing and pathway analysis identify important pathways involved in hypertrichosis and intellectual disability in patients with wiedemann–steiner syndrome. NeuroMolecular Medicine, 20:409-417, Jul 2018. URL: https://doi.org/10.1007/s12017-018-8502-1, doi:10.1007/s12017-018-8502-1. This article has 9 citations and is from a peer-reviewed journal.

  21. (vallianatos2020mutuallysuppressiveroles pages 1-2): Christina N. Vallianatos, Brynne Raines, Robert S. Porter, Katherine M. Bonefas, Michael C. Wu, Patricia M. Garay, Katie M. Collette, Young Ah Seo, Yali Dou, Catherine E. Keegan, Natalie C. Tronson, and Shigeki Iwase. Mutually suppressive roles of kmt2a and kdm5c in behaviour, neuronal structure, and histone h3k4 methylation. Communications Biology, Mar 2020. URL: https://doi.org/10.1038/s42003-020-1001-6, doi:10.1038/s42003-020-1001-6. This article has 61 citations and is from a peer-reviewed journal.

  22. (mendoza2020physicaltherapymanagement pages 1-2): Carmel Mendoza. Physical therapy management of wiedemann-steiner syndrome from birth to 3 years. Pediatric Physical Therapy, 32:E64-E69, Jul 2020. URL: https://doi.org/10.1097/pep.0000000000000714, doi:10.1097/pep.0000000000000714. This article has 6 citations and is from a peer-reviewed journal.

  23. (baer2018wiedemann‐steinersyndromeas pages 10-11): S. Baer, A. Afenjar, T. Smol, A. Piton, B. Gérard, Y. Alembik, T. Bienvenu, G. Boursier, O. Boute, C. Colson, M.‐P. Cordier, V. Cormier‐Daire, B. Delobel, M. Doco‐Fenzy, B. Duban‐Bedu, M. Fradin, D. Geneviève, A. Goldenberg, M. Grelet, D. Haye, D. Heron, B. Isidor, B. Keren, D. Lacombe, A.‐S. Lèbre, G. Lesca, A. Masurel, M. Mathieu‐Dramard, C. Nava, L. Pasquier, A. Petit, N. Philip, J. Piard, S. Rondeau, P. Saugier‐Veber, S. Sukno, J. Thevenon, J. Van‐Gils, C. Vincent‐Delorme, M. Willems, E. Schaefer, and G. Morin. Wiedemann‐steiner syndrome as a major cause of syndromic intellectual disability: a study of 33 french cases. Clinical Genetics, 94:141-152, Jul 2018. URL: https://doi.org/10.1111/cge.13254, doi:10.1111/cge.13254. This article has 92 citations and is from a peer-reviewed journal.

  24. (kim2023growthhormonedeficiency pages 1-2): Mi Ra Kim, Eun-Gyong Yoo, Seonkyeong Rhie, Go Hun Seo, and Mo Kyung Jung. Growth hormone deficiency in a boy with wiedemann-steiner syndrome: a case report and review. Annals of Pediatric Endocrinology & Metabolism, 28:S25-S28, Dec 2023. URL: https://doi.org/10.6065/apem.2244052.026, doi:10.6065/apem.2244052.026. This article has 5 citations.

  25. (wang2025diagnosisandrecombinant pages 1-2): Mengqin Wang, Jiaqian Hu, Zixia Zhang, Xi Wang, Shuxian Yuan, Yixuan Zhao, Yingxian Zhang, Haiyan Wei, Jiajia Chen, Yaodong Zhang, and Yongxing Chen. Diagnosis and recombinant human growth hormone treatment of wiedemann–steiner syndrome: discovery of novel kmt2a variants and review of existing literature. BMC Pediatrics, Jul 2025. URL: https://doi.org/10.1186/s12887-025-05751-0, doi:10.1186/s12887-025-05751-0. This article has 3 citations and is from a peer-reviewed journal.

  26. (vallianatos2020mutuallysuppressiveroles pages 2-3): Christina N. Vallianatos, Brynne Raines, Robert S. Porter, Katherine M. Bonefas, Michael C. Wu, Patricia M. Garay, Katie M. Collette, Young Ah Seo, Yali Dou, Catherine E. Keegan, Natalie C. Tronson, and Shigeki Iwase. Mutually suppressive roles of kmt2a and kdm5c in behaviour, neuronal structure, and histone h3k4 methylation. Communications Biology, Mar 2020. URL: https://doi.org/10.1038/s42003-020-1001-6, doi:10.1038/s42003-020-1001-6. This article has 61 citations and is from a peer-reviewed journal.

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