Koolen-de Vries syndrome is a multisystem neurodevelopmental disorder caused by KANSL1 haploinsufficiency, either through a recurrent 17q21.31 microdeletion encompassing KANSL1 or a heterozygous pathogenic KANSL1 variant. Core manifestations include hypotonia, global developmental delay, moderate intellectual disability, marked expressive language impairment, and a characteristic craniofacial and behavioral phenotype with additional structural brain, cardiac, urogenital, and musculoskeletal anomalies in a subset of affected individuals.
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name: Koolen-de Vries syndrome
creation_date: '2026-04-09T17:11:02Z'
updated_date: '2026-05-09T20:37:58Z'
category: Mendelian
description: >
Koolen-de Vries syndrome is a multisystem neurodevelopmental disorder caused
by KANSL1 haploinsufficiency, either through a recurrent 17q21.31
microdeletion encompassing KANSL1 or a heterozygous pathogenic KANSL1
variant. Core manifestations include hypotonia, global developmental delay,
moderate intellectual disability, marked expressive language impairment, and a
characteristic craniofacial and behavioral phenotype with additional
structural brain, cardiac, urogenital, and musculoskeletal anomalies in a
subset of affected individuals.
disease_term:
preferred_term: Koolen-de Vries syndrome
term:
id: MONDO:0012496
label: Koolen-de Vries syndrome
parents:
- Neurodevelopmental disorder
- Chromatin disorder
synonyms:
- KdVS
- 17q21.31 microdeletion syndrome
- KANSL1 haploinsufficiency syndrome
inheritance:
- name: Autosomal dominant inheritance
inheritance_term:
preferred_term: Autosomal dominant inheritance
term:
id: HP:0000006
label: Autosomal dominant inheritance
expressivity: VARIABLE
description: >
KdVS is caused by heterozygous loss of KANSL1 function, usually arising de
novo through either a recurrent 17q21.31 deletion or a loss-of-function
KANSL1 sequence variant.
evidence:
- reference: PMID:41457108
reference_title: "Improving variant interpretation and diagnosis in Koolen-de Vries syndrome through a curated genotype-phenotype repository."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "(KdVS), an autosomal dominant NDD caused by KANSL1 haploinsufficiency"
explanation: Supports autosomal dominant inheritance mediated by KANSL1 haploinsufficiency.
prevalence:
- population: Historically estimated general population prevalence
percentage: ~1 in 16,000
notes: >
This estimate comes from early microdeletion ascertainment studies and is
likely conservative because the syndrome was considered substantially
underdiagnosed. True prevalence of all KANSL1-related molecular classes
remains uncertain.
evidence:
- reference: PMID:18628315
reference_title: "Clinical and molecular delineation of the 17q21.31 microdeletion syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "We estimate the prevalence of the syndrome to be 1 in 16,000 and show that it is highly underdiagnosed."
explanation: Provides the widely cited historical prevalence estimate and explicitly notes underdiagnosis.
pathophysiology:
- name: KANSL1 haploinsufficiency
description: >
Heterozygous loss of KANSL1 is the core molecular lesion in KdVS. KANSL1 is
a chromatin-associated regulator within the NSL complex, linking reduced
dosage to altered chromatin organization and transcriptional control during
brain development.
genes:
- preferred_term: KANSL1
term:
id: hgnc:24565
label: KANSL1
cell_types:
- preferred_term: neuron
term:
id: CL:0000540
label: neuron
biological_processes:
- preferred_term: chromatin organization
term:
id: GO:0006325
label: chromatin organization
- preferred_term: regulation of gene expression
term:
id: GO:0010468
label: regulation of gene expression
modifier: DECREASED
locations:
- preferred_term: brain
term:
id: UBERON:0000955
label: brain
downstream:
- target: Autophagosome accumulation in KANSL1-deficient neurons
description: Reduced KANSL1 dosage perturbs neuronal homeostatic programs that culminate in autophagosome accumulation.
evidence:
- reference: PMID:22544367
reference_title: "Mutations in KANSL1 cause the 17q21.31 microdeletion syndrome phenotype."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "These findings indicate that 17q21.31 deletion syndrome is a monogenic disorder caused by haploinsufficiency of KANSL1."
explanation: Establishes KANSL1 haploinsufficiency as the disease-defining mechanism.
- reference: PMID:22544363
reference_title: "Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The KANSL1 protein is an evolutionarily conserved regulator of the chromatin modifier KAT8, which influences gene expression through histone H4 lysine 16 (H4K16) acetylation."
explanation: Supports the chromatin and transcriptional regulatory role of KANSL1 underlying KdVS biology.
- name: Autophagosome accumulation in KANSL1-deficient neurons
description: >
In KANSL1-deficient human neurons, reduced SOD1 is associated with increased
oxidative stress and subsequent autophagosome accumulation, including at
excitatory synapses.
genes:
- preferred_term: KANSL1
term:
id: hgnc:24565
label: KANSL1
cell_types:
- preferred_term: neuron
term:
id: CL:0000540
label: neuron
biological_processes:
- preferred_term: autophagy
term:
id: GO:0006914
label: autophagy
modifier: INCREASED
locations:
- preferred_term: brain
term:
id: UBERON:0000955
label: brain
downstream:
- target: Synaptic dysfunction in KANSL1-deficient neurons
description: Autophagosome accumulation at excitatory synapses precedes impaired synaptic transmission and neuronal network activity.
evidence:
- reference: PMID:34286667
reference_title: "Imbalanced autophagy causes synaptic deficits in a human model for neurodevelopmental disorders."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: "we identified SOD1 (superoxide dismutase 1), an antioxidant enzyme, to be significantly decreased, leading to a subsequent increase in oxidative stress and autophagosome accumulation."
explanation: Supports oxidative-stress-associated autophagy imbalance in KANSL1-deficient neurons.
- name: Synaptic dysfunction in KANSL1-deficient neurons
description: >
Autophagosome accumulation at excitatory synapses in KANSL1-deficient
neurons is associated with reduced synaptic density, decreased AMPA
receptor-mediated transmission, and impaired neuronal network activity.
genes:
- preferred_term: KANSL1
term:
id: hgnc:24565
label: KANSL1
cell_types:
- preferred_term: neuron
term:
id: CL:0000540
label: neuron
biological_processes:
- preferred_term: chemical synaptic transmission
term:
id: GO:0007268
label: chemical synaptic transmission
modifier: DECREASED
locations:
- preferred_term: brain
term:
id: UBERON:0000955
label: brain
evidence:
- reference: PMID:34286667
reference_title: "Imbalanced autophagy causes synaptic deficits in a human model for neurodevelopmental disorders."
supports: SUPPORT
evidence_source: IN_VITRO
snippet: "In KANSL1-deficient neurons, autophagosome accumulation at excitatory synapses resulted in reduced synaptic density, reduced GRIA/AMPA receptor-mediated transmission and impaired neuronal network activity."
explanation: Directly links autophagosome accumulation to synaptic and network dysfunction in a human neuronal model.
phenotypes:
- category: Cognitive
name: Global developmental delay
frequency: VERY_FREQUENT
diagnostic: true
description: >
Global developmental delay is a core and usually early-recognized feature of
KdVS.
phenotype_term:
preferred_term: Global developmental delay
term:
id: HP:0001263
label: Global developmental delay
evidence:
- reference: PMID:26306646
reference_title: "The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The Koolen-de Vries syndrome (KdVS; OMIM #610443), also known as the 17q21.31 microdeletion syndrome, is a clinically heterogeneous disorder characterised by (neonatal) hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism."
explanation: Large cohort summary identifies developmental delay as a defining syndrome feature.
- category: Cognitive
name: Intellectual disability
frequency: VERY_FREQUENT
diagnostic: true
description: >
Intellectual disability is typically moderate but varies across affected
individuals.
phenotype_term:
preferred_term: Intellectual disability
term:
id: HP:0001249
label: Intellectual disability
evidence:
- reference: PMID:26306646
reference_title: "The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The Koolen-de Vries syndrome (KdVS; OMIM #610443), also known as the 17q21.31 microdeletion syndrome, is a clinically heterogeneous disorder characterised by (neonatal) hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism."
explanation: Large cohort summary identifies moderate intellectual disability as a core syndrome manifestation.
- category: Neurologic
name: Hypotonia
frequency: VERY_FREQUENT
diagnostic: true
description: >
Hypotonia is usually evident from infancy and is among the most recognizable
early clinical findings.
phenotype_term:
preferred_term: Hypotonia
term:
id: HP:0001252
label: Hypotonia
evidence:
- reference: PMID:18628315
reference_title: "Clinical and molecular delineation of the 17q21.31 microdeletion syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Extensive clinical examination reveals that developmental delay, hypotonia, facial dysmorphisms including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, and a friendly/amiable behaviour are the most characteristic features."
explanation: Founding syndrome series identifies hypotonia as one of the most characteristic findings.
- category: Communication
name: Expressive language delay
frequency: VERY_FREQUENT
description: >
Expressive language is disproportionately impaired relative to receptive
language and motor development.
phenotype_term:
preferred_term: Expressive language delay
term:
id: HP:0002474
label: Expressive language delay
evidence:
- reference: PMID:26306646
reference_title: "The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Expressive language development is particularly impaired compared with receptive language or motor skills."
explanation: Directly supports the characteristic disproportionate expressive-language deficit in KdVS.
- category: Neurologic
name: Seizures
frequency: FREQUENT
description: >
Epilepsy commonly begins in childhood and often features prolonged focal
seizures with autonomic features.
phenotype_term:
preferred_term: Seizure
term:
id: HP:0001250
label: Seizure
evidence:
- reference: PMID:28440867
reference_title: "The epileptology of Koolen-de Vries syndrome: Electro-clinico-radiologic findings in 31 patients."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The typical epilepsy phenotype of KdVS involves childhood-onset focal seizures that are prolonged and have prominent autonomic features."
explanation: Defines the characteristic seizure phenotype in a dedicated KdVS epilepsy cohort.
- category: Cardiovascular
name: Congenital heart defects
frequency: FREQUENT
description: >
Structural heart defects are part of the recurrent multisystem anomaly
spectrum in KdVS.
phenotype_term:
preferred_term: Congenital heart defect
term:
id: HP:0001627
label: Abnormal heart morphology
evidence:
- reference: PMID:26306646
reference_title: "The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Other frequently reported features include social and friendly behaviour, epilepsy, musculoskeletal anomalies, congenital heart defects, urogenital malformations, and ectodermal anomalies."
explanation: Large cohort summary lists congenital heart defects among the recurrent multisystem manifestations.
- category: Structural
name: Abnormal corpus callosum morphology
description: >
Structural brain anomalies, including corpus callosum dysgenesis, are
common on neuroimaging in the epilepsy-enriched KdVS cohort.
phenotype_term:
preferred_term: Abnormal corpus callosum morphology
term:
id: HP:0001273
label: Abnormal corpus callosum morphology
evidence:
- reference: PMID:28440867
reference_title: "The epileptology of Koolen-de Vries syndrome: Electro-clinico-radiologic findings in 31 patients."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Corpus callosum dysgenesis, abnormal hippocampi, and dilated ventricles were the most common"
explanation: Neuroimaging review in the KdVS epilepsy cohort identifies corpus callosum dysgenesis as a recurrent structural brain anomaly.
genetic:
- name: KANSL1
gene_term:
preferred_term: KANSL1
term:
id: hgnc:24565
label: KANSL1
association: Causative
notes: >
Heterozygous loss of KANSL1 function, whether from a recurrent 17q21.31
deletion or a pathogenic sequence variant, is sufficient to cause the full
KdVS phenotype. Clinically important phenotypic differences between
microdeletion and sequence-variant cases have not been established.
evidence:
- reference: PMID:26306646
reference_title: "The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Comparison of the phenotype of both the microdeletion and SNV patients does not show differences of clinical importance, stressing that haploinsufficiency of KANSL1 is sufficient to cause the full KdVS phenotype."
explanation: Supports KANSL1 haploinsufficiency as sufficient across the major molecular classes of KdVS.
- reference: CGGV:assertion_e89a0e87-314a-49b1-bb50-6b26aeaa1037-2022-02-18T120936.714Z
reference_title: "KANSL1 / Koolen-de Vries syndrome (Definitive)"
supports: SUPPORT
evidence_source: OTHER
snippet: "KANSL1 | HGNC:24565 | Koolen-de Vries syndrome | MONDO:0012496 | AD | Definitive"
explanation: ClinGen classifies the KANSL1-Koolen-de Vries syndrome gene-disease relationship as definitive with autosomal dominant inheritance.
biochemical:
- name: Blood DNA methylation episignature
presence: Positive
context: Diagnostic biomarker for molecular confirmation and missense/VUS classification
notes: >
Whole-blood DNA methylation profiling identifies a reproducible KdVS
episignature that can support diagnosis and variant interpretation in the
structurally complex KANSL1 region.
evidence:
- reference: PMID:38282074
reference_title: "A new blood DNA methylation signature for Koolen-de Vries syndrome: Classification of missense KANSL1 variants and comparison to fibroblast cells."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "In this study, we identified a robust DNAm signature of 456 significant CpG sites in 8 individuals with KdVS, a pattern independently validated in an additional 7 individuals with KdVS."
explanation: Supports a reproducible blood DNA methylation signature as a diagnostic biomarker in KdVS.
treatments: []
references:
- reference: DOI:10.1002/ajmg.a.62008
title: 'Koolen‐de Vries syndrome: First report of two unrelated Indian patients'
found_in:
- Koolen_de_Vries_syndrome-deep-research-falcon.md
findings:
- statement: Koolen‐de Vries syndrome is a recurrent microdeletion syndrome caused due to deletion of around 400–600 kb region at 17q21.31.
supporting_text: Koolen‐de Vries syndrome is a recurrent microdeletion syndrome caused due to deletion of around 400–600 kb region at 17q21.31.
evidence:
- reference: DOI:10.1002/ajmg.a.62008
reference_title: 'Koolen‐de Vries syndrome: First report of two unrelated Indian patients'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Koolen‐de Vries syndrome is a recurrent microdeletion syndrome caused due to deletion of around 400–600 kb region at 17q21.31.
explanation: Deep research cited this publication as relevant literature for Koolen de Vries syndrome.
- reference: DOI:10.1002/ajmg.a.62536
title: 'Koolen‐de Vries syndrome in a 63‐year‐old woman: Report of the oldest patient and a review of the adult phenotype'
found_in:
- Koolen_de_Vries_syndrome-deep-research-falcon.md
findings:
- statement: Koolen‐de Vries syndrome (KdVS) is a rare genetic disorder caused by a de novo microdeletion in chromosomal region 17q21.31 encompassing KANSL1 or by a de novo intragenic pathogenic variant of KANSL1.
supporting_text: Koolen‐de Vries syndrome (KdVS) is a rare genetic disorder caused by a de novo microdeletion in chromosomal region 17q21.31 encompassing KANSL1 or by a de novo intragenic pathogenic variant of KANSL1.
evidence:
- reference: DOI:10.1002/ajmg.a.62536
reference_title: 'Koolen‐de Vries syndrome in a 63‐year‐old woman: Report of the oldest patient and a review of the adult phenotype'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Koolen‐de Vries syndrome (KdVS) is a rare genetic disorder caused by a de novo microdeletion in chromosomal region 17q21.31 encompassing KANSL1 or by a de novo intragenic pathogenic variant of KANSL1.
explanation: Deep research cited this publication as relevant literature for Koolen de Vries syndrome.
- reference: DOI:10.1016/j.gimo.2023.100817
title: GenIDA, a participatory patient registry for genetic forms of intellectual disability provides detailed caregiver-reported information on 237 individuals with Koolen-de Vries syndrome
found_in:
- Koolen_de_Vries_syndrome-deep-research-falcon.md
findings:
- statement: GenIDA, a participatory patient registry for genetic forms of intellectual disability provides detailed caregiver-reported information on 237 individuals with Koolen-de Vries syndrome
supporting_text: GenIDA, a participatory patient registry for genetic forms of intellectual disability provides detailed caregiver-reported information on 237 individuals with Koolen-de Vries syndrome
- reference: DOI:10.1038/s41431-022-01230-7
title: 'Expanding the speech and language phenotype in Koolen-de Vries syndrome: late onset and periodic stuttering a novel feature'
found_in:
- Koolen_de_Vries_syndrome-deep-research-falcon.md
findings:
- statement: 'Expanding the speech and language phenotype in Koolen-de Vries syndrome: late onset and periodic stuttering a novel feature'
supporting_text: 'Expanding the speech and language phenotype in Koolen-de Vries syndrome: late onset and periodic stuttering a novel feature'
- reference: DOI:10.1038/s41431-024-01538-6
title: 'A new blood DNA methylation signature for Koolen-de Vries syndrome: Classification of missense KANSL1 variants and comparison to fibroblast cells'
found_in:
- Koolen_de_Vries_syndrome-deep-research-falcon.md
findings:
- statement: 'A new blood DNA methylation signature for Koolen-de Vries syndrome: Classification of missense KANSL1 variants and comparison to fibroblast cells'
supporting_text: 'A new blood DNA methylation signature for Koolen-de Vries syndrome: Classification of missense KANSL1 variants and comparison to fibroblast cells'
- reference: DOI:10.1038/s41467-022-28613-0
title: Kansl1 haploinsufficiency impairs autophagosome-lysosome fusion and links autophagic dysfunction with Koolen-de Vries syndrome in mice
found_in:
- Koolen_de_Vries_syndrome-deep-research-falcon.md
findings:
- statement: Koolen-de Vries syndrome (KdVS) is a rare disorder caused by haploinsufficiency of KAT8 regulatory NSL complex subunit 1 (KANSL1), which is characterized by intellectual disability, heart failure, hypotonia, and congenital malformations.
supporting_text: Koolen-de Vries syndrome (KdVS) is a rare disorder caused by haploinsufficiency of KAT8 regulatory NSL complex subunit 1 (KANSL1), which is characterized by intellectual disability, heart failure, hypotonia, and congenital malformations.
evidence:
- reference: DOI:10.1038/s41467-022-28613-0
reference_title: Kansl1 haploinsufficiency impairs autophagosome-lysosome fusion and links autophagic dysfunction with Koolen-de Vries syndrome in mice
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: Koolen-de Vries syndrome (KdVS) is a rare disorder caused by haploinsufficiency of KAT8 regulatory NSL complex subunit 1 (KANSL1), which is characterized by intellectual disability, heart failure, hypotonia, and congenital malformations.
explanation: Deep research cited this publication as relevant literature for Koolen de Vries syndrome.
- reference: DOI:10.1080/13816810.2020.1868012
title: Ocular manifestations and surgical interventions in pediatric patients with Koolen-de-Vries syndrome
found_in:
- Koolen_de_Vries_syndrome-deep-research-falcon.md
findings:
- statement: Ocular manifestations and surgical interventions in pediatric patients with Koolen-de-Vries syndrome
supporting_text: Ocular manifestations and surgical interventions in pediatric patients with Koolen-de-Vries syndrome
- reference: DOI:10.1080/15548627.2021.1936777
title: Imbalanced autophagy causes synaptic deficits in a human model for neurodevelopmental disorders
found_in:
- Koolen_de_Vries_syndrome-deep-research-falcon.md
findings:
- statement: Imbalanced autophagy causes synaptic deficits in a human model for neurodevelopmental disorders
supporting_text: Imbalanced autophagy causes synaptic deficits in a human model for neurodevelopmental disorders
- reference: DOI:10.1177/26330040241265414
title: 'Koolen-de Vries Syndrome: a journey from diagnosis to treatments'
found_in:
- Koolen_de_Vries_syndrome-deep-research-falcon.md
findings:
- statement: The Koolen-de Vries Syndrome Foundation was founded in 2013 with the mission to educate, increase awareness, promote research and develop treatments for individuals living with Koolen-de Vries Syndrome (KdVS) and their families.
supporting_text: The Koolen-de Vries Syndrome Foundation was founded in 2013 with the mission to educate, increase awareness, promote research and develop treatments for individuals living with Koolen-de Vries Syndrome (KdVS) and their families.
evidence:
- reference: DOI:10.1177/26330040241265414
reference_title: 'Koolen-de Vries Syndrome: a journey from diagnosis to treatments'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The Koolen-de Vries Syndrome Foundation was founded in 2013 with the mission to educate, increase awareness, promote research and develop treatments for individuals living with Koolen-de Vries Syndrome (KdVS) and their families.
explanation: Deep research cited this publication as relevant literature for Koolen de Vries syndrome.
- reference: DOI:10.7759/cureus.79194
title: 'Neuroimaging of Koolen-De Vries Syndrome: A Rare Genetic Disorder'
found_in:
- Koolen_de_Vries_syndrome-deep-research-falcon.md
findings:
- statement: 'Neuroimaging of Koolen-De Vries Syndrome: A Rare Genetic Disorder'
supporting_text: 'Neuroimaging of Koolen-De Vries Syndrome: A Rare Genetic Disorder'
Koolen–de Vries syndrome is a rare, multisystem neurodevelopmental disorder caused by either a recurrent 17q21.31 microdeletion that includes KANSL1 or by a heterozygous intragenic pathogenic variant in KANSL1. Core features across cohorts include developmental delay, hypotonia, intellectual disability (often moderate), speech/language disorder, and frequent multisystem comorbidities (cardiac, renal/urogenital, musculoskeletal, sensory, sleep, and behavioral features). (colin2023genidaaparticipatory pages 2-3, houser2025neuroimagingofkoolende pages 2-8)
Commonly used synonyms in the clinical literature include: - 17q21.31 microdeletion syndrome (farne2022koolen‐devriessyndrome pages 10-12) - KANSL1-related intellectual disability syndrome (farne2022koolen‐devriessyndrome pages 10-12)
The report integrates: - Aggregated disease-level resources via cohorts/registries: e.g., GenIDA caregiver-reported cohort (n=237) (colin2023genidaaparticipatory pages 3-4) - Clinician-assessed cohort study: large speech/language and medical phenotype cohort (n=81) (john2023expandingthespeech pages 2-2) - Primary mechanistic studies: mouse model and human iPSC-derived neuronal models (li2022kansl1haploinsufficiencyimpairs pages 1-2, linda2022imbalancedautophagycauses pages 1-3)
KdVS is a genetic disorder caused by KANSL1 haploinsufficiency, either from: - a 17q21.31 deletion including KANSL1, or - a heterozygous pathogenic variant in KANSL1 (houser2025neuroimagingofkoolende pages 2-8, colin2023genidaaparticipatory pages 2-3)
KdVS is described as autosomal dominant, typically arising de novo (houser2025neuroimagingofkoolende pages 2-8, saxena2021koolen‐devriessyndrome pages 2-4).
Two major recent data sources provide quantitative phenotype frequencies: - GenIDA caregiver registry (n=237; mean age 14.0 years; 116 males/121 females) (colin2023genidaaparticipatory pages 3-4) - St John et al. 2023 clinical cohort (n=81; mean age 9y10mo; age range 1.5–40.2y) (john2023expandingthespeech pages 2-2)
The 2023 speech/language cohort reported relative strengths in social competence and behavioral/emotional control, but communication difficulties impacted daily living skills (john2023expandingthespeech pages 1-2).
A 2024 European Journal of Human Genetics study identified a blood DNA methylation episignature of 456 CpG sites for KdVS and used an SVM classifier to support diagnosis and classify KANSL1 VUS (awamleh2024anewblood pages 1-2, awamleh2024anewblood pages 2-3).
No specific environmental contributors, protective factors, or infectious triggers were supported by the retrieved KdVS-focused evidence.
KANSL1 haploinsufficiency → dysregulated chromatin/NSL complex function and H4K16 acetylation → transcriptional dysregulation of autophagy machinery and cellular homeostasis → oxidative stress, impaired lysosomal/autophagic clearance and synaptic dysfunction → neurodevelopmental phenotype; plus cardiac dysfunction in mouse models. (linda2022imbalancedautophagycauses pages 1-3, li2022kansl1haploinsufficiencyimpairs pages 1-2)
In KANSL1-deficient human iPSC-derived neurons, decreased SOD1 leads to increased oxidative stress and autophagosome accumulation; autophagosomes accumulate at excitatory synapses with reduced synaptic density and reduced AMPA receptor-mediated transmission, impairing network activity. Antioxidant/oxidative stress reduction rescued autophagosomes and neuronal function. (linda2022imbalancedautophagycauses pages 1-3)
Direct abstract quotes (primary literature): - “In KANSL1-deficient neurons, autophagosome accumulation at excitatory synapses resulted in reduced synaptic density, reduced GRIA/AMPA receptor-mediated transmission and impaired neuronal network activity.” (linda2022imbalancedautophagycauses pages 1-3) - “By pharmacologically reducing oxidative stress, we could rescue the aberrant autophagosome formation as well as synaptic and neuronal network activity in KANSL1-deficient neurons.” (linda2022imbalancedautophagycauses pages 1-3)
A Nature Communications mouse study identified KANSL1 as essential for autophagy and showed KANSL1 modulates autophagosome–lysosome fusion via transcriptional regulation of STX17. Kansl1+/− mice show impaired clearance of damaged mitochondria, increased ROS, and neuronal/cardiac dysfunction; 13-cis retinoic acid reversed mitophagic defects and neurobehavioral abnormalities. (li2022kansl1haploinsufficiencyimpairs pages 1-2)
From cohort data, the primary impacted system is the nervous system, with frequent multisystem involvement: - CNS/neurodevelopment: developmental delay, ID, seizures; imaging anomalies in a subset (john2023expandingthespeech pages 2-2) - Cardiac: ASD/VSD and other defects in substantial fractions (colin2023genidaaparticipatory pages 3-4, john2023expandingthespeech pages 2-2) - Renal/urogenital: relatively common (colin2023genidaaparticipatory pages 3-4) - Musculoskeletal: hypermobility/scoliosis, etc. (colin2023genidaaparticipatory pages 7-9)
Diagnosis is molecular and includes: - Chromosomal microarray (CMA) to detect 17q21.31 deletions - Single-gene testing / multigene panels for KANSL1 variants - Broader genomic approaches when phenotype is atypical (houser2025neuroimagingofkoolende pages 2-8)
A 2024 study developed a blood DNA methylation episignature (456 CpGs) and demonstrated diagnostic utility for classification of KANSL1 VUS and atypical cases, with validation case scores 75–92% vs controls 0–13%. (awamleh2024anewblood pages 2-3, awamleh2024anewblood pages 1-2)
Direct abstract quote (Awamleh 2024): “In this study, we identified a robust DNAm signature of 456 significant CpG sites…” (awamleh2024anewblood pages 1-2)
Differential diagnoses are not systematically enumerated in the retrieved evidence; however, KdVS is placed among syndromic neurodevelopmental disorders with overlapping features, and facial/speech phenotyping tools are used in the broader field (e.g., NDD cohorts referenced indirectly). Evidence in this run is insufficient to list a complete differential.
There is no curative therapy described in clinical summaries; management is symptomatic and multidisciplinary, including physiotherapy for motor delays, speech/feeding therapy, and educational supports, with multispecialty monitoring (houser2025neuroimagingofkoolende pages 2-8).
Speech/language recommendations (2023 cohort) emphasize early AAC and ongoing targeted therapy across development. (john2023expandingthespeech pages 1-2)
Caregiver-reported medication effectiveness in GenIDA suggested reported efficacy for valproate (83%) and levetiracetam (67% good efficacy among reporters), with additional reported effectiveness of valproate and oxcarbazepine at cohort level. (colin2023genidaaparticipatory pages 7-9, colin2023genidaaparticipatory pages 1-2)
A 2024 review describing the KdVS Foundation’s strategy emphasizes models, registries, natural history, and translational funding, with a stated goal of a first clinical trial in late 2026. (pfalzer2024koolendevriessyndrome pages 2-3)
Primary prevention is not applicable to the de novo genetic cause, but genetic counseling is relevant given the autosomal dominant, typically de novo etiology. (houser2025neuroimagingofkoolende pages 2-8, saxena2021koolen‐devriessyndrome pages 2-4)
No evidence of naturally occurring KdVS-equivalent disease in non-human species was retrieved. KANSL1 is conserved and studied in model organisms, but veterinary natural disease evidence is not available in the retrieved texts.
The following artifact condenses the key actionable facts (identifiers, genetics, prevalence, phenotype frequencies, and 2024 diagnostic episignature metrics) with URLs and publication dates.
| Category | Data point | Value/description | Source (author/year/journal) | URL | Pub date |
|---|---|---|---|---|---|
| Disease information | Primary disease name | Koolen-de Vries syndrome (KdVS); rare multisystem neurodevelopmental disorder caused by 17q21.31 deletion including KANSL1 or heterozygous intragenic KANSL1 pathogenic variant (colin2023genidaaparticipatory pages 2-3, houser2025neuroimagingofkoolende pages 2-8) | Colin et al. 2023, Genetics in Medicine Open; Houser et al. 2025, Cureus | https://doi.org/10.1016/j.gimo.2023.100817; https://doi.org/10.7759/cureus.79194 | 2023-01; 2025-02 |
| Disease information | Key identifier | OMIM 610443 (reported in GenIDA KdVS cohort excerpt) (colin2023genidaaparticipatory pages 2-3) | Colin et al. 2023, Genetics in Medicine Open | https://doi.org/10.1016/j.gimo.2023.100817 | 2023-01 |
| Disease information | Common synonyms | 17q21.31 microdeletion syndrome; KANSL1-related intellectual disability syndrome (colin2023genidaaparticipatory pages 2-3, farne2022koolen‐devriessyndrome pages 10-12) | Colin et al. 2023, Genetics in Medicine Open; Farnè et al. 2022, Am J Med Genet A | https://doi.org/10.1016/j.gimo.2023.100817; https://doi.org/10.1002/ajmg.a.62536 | 2023-01; 2022-10 |
| Genetic etiology | Typical recurrent deletion | Typical recurrent 17q21.31 deletion ~500–650 kb; cohort wording also notes recurrent deletion spanning ~43.7–44.25 Mb region (john2023expandingthespeech pages 3-4, houser2025neuroimagingofkoolende pages 2-8) | St John et al. 2023, Eur J Hum Genet; Houser et al. 2025, Cureus | https://doi.org/10.1038/s41431-022-01230-7; https://doi.org/10.7759/cureus.79194 | 2023-12; 2025-02 |
| Genetic etiology | Deletion vs sequence variant proportion | About 60% due to heterozygous 17q21.31 deletion and 40% due to KANSL1 sequence variants in one review excerpt (houser2025neuroimagingofkoolende pages 2-8) | Houser et al. 2025, Cureus | https://doi.org/10.7759/cureus.79194 | 2025-02 |
| Genetic etiology | GenIDA genotype counts | In GenIDA cohort, 157 individuals with 17q21.31 deletion and 40 with pathogenic KANSL1 variant; no major clinical differences detected between groups (colin2023genidaaparticipatory pages 2-3) | Colin et al. 2023, Genetics in Medicine Open | https://doi.org/10.1016/j.gimo.2023.100817 | 2023-01 |
| Genetic etiology | 2023 speech cohort genotype counts | In speech/language cohort (n=81), 56/81 (69.1%) had typical 17q21.31 deletion and 19/81 had KANSL1-only sequence variants; no group score differences reported between deletion and KANSL1-variant groups (john2023expandingthespeech pages 2-2, john2023expandingthespeech pages 3-4) | St John et al. 2023, Eur J Hum Genet | https://doi.org/10.1038/s41431-022-01230-7 | 2023-12 |
| Genetic etiology | Variant classes observed | Predominantly loss-of-function intragenic variants: truncating, frameshift, splice-site, small intragenic exon deletion; 2024 episignature study also discusses missense/nonsense/frameshift/deletion-insertion/mosaic variants for classification (john2023expandingthespeech pages 3-4, awamleh2024anewblood pages 3-5) | St John et al. 2023, Eur J Hum Genet; Awamleh et al. 2024, Eur J Hum Genet | https://doi.org/10.1038/s41431-022-01230-7; https://doi.org/10.1038/s41431-024-01538-6 | 2023-12; 2024-01 |
| Inheritance/epidemiology | Inheritance pattern | Autosomal dominant; typically de novo disease mechanism highlighted in KdVS descriptions (houser2025neuroimagingofkoolende pages 2-8, prat2021ocularmanifestationsand pages 4-4, saxena2021koolen‐devriessyndrome pages 2-4) | Houser et al. 2025, Cureus; Prat et al. 2021, Ophthalmic Genetics; Saxena et al. 2021, Am J Med Genet A | https://doi.org/10.7759/cureus.79194; https://doi.org/10.1080/13816810.2020.1868012; https://doi.org/10.1002/ajmg.a.62008 | 2025-02; 2021-01; 2021-12 |
| Inheritance/epidemiology | Estimated prevalence | Estimated prevalence for 17q21.31 deletion approximately 1:55,000 births (houser2025neuroimagingofkoolende pages 2-8, prat2021ocularmanifestationsand pages 4-4) | Houser et al. 2025, Cureus; Prat et al. 2021, Ophthalmic Genetics | https://doi.org/10.7759/cureus.79194; https://doi.org/10.1080/13816810.2020.1868012 | 2025-02; 2021-01 |
| Epidemiology | Sex distribution in GenIDA | 116 males / 121 females; mean age 14.0 years in GenIDA cohort (colin2023genidaaparticipatory pages 3-4) | Colin et al. 2023, Genetics in Medicine Open | https://doi.org/10.1016/j.gimo.2023.100817 | 2023-01 |
| Epidemiology | Sex/age in speech cohort | 35 female / 46 male; age 1.5–40.2 years, mean 9 years 10 months (john2023expandingthespeech pages 2-2) | St John et al. 2023, Eur J Hum Genet | https://doi.org/10.1038/s41431-022-01230-7 | 2023-12 |
| Phenotypes (GenIDA 2023) | Prenatal/perinatal problems | 77.9% (colin2023genidaaparticipatory pages 3-4) | Colin et al. 2023, Genetics in Medicine Open | https://doi.org/10.1016/j.gimo.2023.100817 | 2023-01 |
| Phenotypes (GenIDA 2023) | Hypotonia | 61.5% (colin2023genidaaparticipatory pages 3-4) | Colin et al. 2023, Genetics in Medicine Open | https://doi.org/10.1016/j.gimo.2023.100817 | 2023-01 |
| Phenotypes (GenIDA 2023) | Feeding difficulties | 60.2% (colin2023genidaaparticipatory pages 3-4) | Colin et al. 2023, Genetics in Medicine Open | https://doi.org/10.1016/j.gimo.2023.100817 | 2023-01 |
| Phenotypes (GenIDA 2023) | Intellectual disability | Formal ID diagnosis in 89.2%; severity: mild 16.9%, moderate 60.2%, severe 2.4%, profound 20.5% (colin2023genidaaparticipatory pages 3-4) | Colin et al. 2023, Genetics in Medicine Open | https://doi.org/10.1016/j.gimo.2023.100817 | 2023-01 |
| Phenotypes (GenIDA 2023) | Epilepsy | 47.3% (97/204) with epilepsy/seizures (colin2023genidaaparticipatory pages 6-7, colin2023genidaaparticipatory pages 3-4) | Colin et al. 2023, Genetics in Medicine Open | https://doi.org/10.1016/j.gimo.2023.100817 | 2023-01 |
| Phenotypes (GenIDA 2023) | Seizure types among seizure cases | Tonic-clonic 38.1%, absence 28.9%, complex partial 22.7%, nocturnal 21.6%, febrile convulsions 19.6%, infantile spasms 14.4%, atonic 9.3% (colin2023genidaaparticipatory pages 6-7) | Colin et al. 2023, Genetics in Medicine Open | https://doi.org/10.1016/j.gimo.2023.100817 | 2023-01 |
| Phenotypes (GenIDA 2023) | Age at first seizure | Average 3.4 years, median 2.0 years (colin2023genidaaparticipatory pages 7-9) | Colin et al. 2023, Genetics in Medicine Open | https://doi.org/10.1016/j.gimo.2023.100817 | 2023-01 |
| Phenotypes (GenIDA 2023) | Speech/language delay | 73.6% in children >2 years; first words average 2.2 years (colin2023genidaaparticipatory pages 3-4) | Colin et al. 2023, Genetics in Medicine Open | https://doi.org/10.1016/j.gimo.2023.100817 | 2023-01 |
| Phenotypes (GenIDA 2023) | Motor milestone delay | Median sit 10.7 mo, stand 17.5 mo, walk 23.4 mo (colin2023genidaaparticipatory pages 3-4) | Colin et al. 2023, Genetics in Medicine Open | https://doi.org/10.1016/j.gimo.2023.100817 | 2023-01 |
| Phenotypes (GenIDA 2023) | Musculoskeletal findings | Joint laxity 50.0%, scoliosis 25.5%, hip dislocation/dysplasia 18.0%, pes planus 22.0%; musculoskeletal anomalies overall 75.5% in later excerpt (colin2023genidaaparticipatory pages 3-4, colin2023genidaaparticipatory pages 7-9) | Colin et al. 2023, Genetics in Medicine Open | https://doi.org/10.1016/j.gimo.2023.100817 | 2023-01 |
| Phenotypes (GenIDA 2023) | Sleep disorders | 42.6% (colin2023genidaaparticipatory pages 3-4) | Colin et al. 2023, Genetics in Medicine Open | https://doi.org/10.1016/j.gimo.2023.100817 | 2023-01 |
| Phenotypes (GenIDA 2023) | Dental problems | 65.1% (colin2023genidaaparticipatory pages 3-4) | Colin et al. 2023, Genetics in Medicine Open | https://doi.org/10.1016/j.gimo.2023.100817 | 2023-01 |
| Phenotypes (GenIDA 2023) | Cardiac anomalies | Atrial septal defect 18.9%; ventricular septal defect 10.9% (colin2023genidaaparticipatory pages 3-4, colin2023genidaaparticipatory pages 6-7) | Colin et al. 2023, Genetics in Medicine Open | https://doi.org/10.1016/j.gimo.2023.100817 | 2023-01 |
| Phenotypes (GenIDA 2023) | Renal/urogenital issues | Approximately 38.3%; male cryptorchidism 22.6% (colin2023genidaaparticipatory pages 3-4, colin2023genidaaparticipatory pages 7-9) | Colin et al. 2023, Genetics in Medicine Open | https://doi.org/10.1016/j.gimo.2023.100817 | 2023-01 |
| Phenotypes (GenIDA 2023) | Vision/hearing | Hypermetropia 38.8%, strabismus 34.7%; hearing problems 40.8%, deafness 12.2% (colin2023genidaaparticipatory pages 6-7) | Colin et al. 2023, Genetics in Medicine Open | https://doi.org/10.1016/j.gimo.2023.100817 | 2023-01 |
| Phenotypes (GenIDA 2023) | Respiratory issues | Respiratory issues 39.8%; laryngomalacia 15.4%; tracheomalacia 8.5%; asthma 16.4%; recurrent pneumonia noted in 13 persons (colin2023genidaaparticipatory pages 6-7, colin2023genidaaparticipatory pages 7-9, colin2023genidaaparticipatory pages 1-2) | Colin et al. 2023, Genetics in Medicine Open | https://doi.org/10.1016/j.gimo.2023.100817 | 2023-01 |
| Phenotypes (GenIDA 2023) | Behavioral profile | Behavioral problems 54.8%; repetitive behaviors 35.2%, attention deficit 32.7%, anxiety 31.2%, obsessive behavior 29.6%, hyperactivity 27.6%; sociable with familiar adults 98.1% and children 88.6% (colin2023genidaaparticipatory pages 6-7, colin2023genidaaparticipatory pages 7-9) | Colin et al. 2023, Genetics in Medicine Open | https://doi.org/10.1016/j.gimo.2023.100817 | 2023-01 |
| Phenotypes (EJHG speech cohort 2023) | Developmental delay | 78/81 (96.3%) (john2023expandingthespeech pages 2-2) | St John et al. 2023, Eur J Hum Genet | https://doi.org/10.1038/s41431-022-01230-7 | 2023-12 |
| Phenotypes (EJHG speech cohort 2023) | Dysmorphic features | 73/81 (90.1%); pear-shaped bulbous nose 48/81 (59.3%) (john2023expandingthespeech pages 2-2) | St John et al. 2023, Eur J Hum Genet | https://doi.org/10.1038/s41431-022-01230-7 | 2023-12 |
| Phenotypes (EJHG speech cohort 2023) | Intellectual disability | Among assessed individuals (n=56), 49/56 (87.5%) had ID; 51.8% moderate, 19.6% severe (john2023expandingthespeech pages 2-2) | St John et al. 2023, Eur J Hum Genet | https://doi.org/10.1038/s41431-022-01230-7 | 2023-12 |
| Phenotypes (EJHG speech cohort 2023) | Structural brain anomalies | 33/62 (53.2%) with imaging had structural brain anomalies (john2023expandingthespeech pages 2-2) | St John et al. 2023, Eur J Hum Genet | https://doi.org/10.1038/s41431-022-01230-7 | 2023-12 |
| Phenotypes (EJHG speech cohort 2023) | Epilepsy/seizures | 29/81 (35.8%) (john2023expandingthespeech pages 2-2) | St John et al. 2023, Eur J Hum Genet | https://doi.org/10.1038/s41431-022-01230-7 | 2023-12 |
| Phenotypes (EJHG speech cohort 2023) | Hearing loss | 24/81 (29.6%), often moderate and conductive (john2023expandingthespeech pages 2-2) | St John et al. 2023, Eur J Hum Genet | https://doi.org/10.1038/s41431-022-01230-7 | 2023-12 |
| Phenotypes (EJHG speech cohort 2023) | Cardiac/musculoskeletal/sleep | Cardiac defects 32/81 (39.5%); musculoskeletal problems 32/81 (39.5%); sleep disturbances 33/81 (40.7%) (john2023expandingthespeech pages 2-2) | St John et al. 2023, Eur J Hum Genet | https://doi.org/10.1038/s41431-022-01230-7 | 2023-12 |
| Phenotypes (EJHG speech cohort 2023) | Other systemic features | Dental problems 36/72 (50.0%); renal/urogenital complications 25/81 (30.9%); GI concerns 24/81 (29.6%); mental health problems 23/81 (28.4%); cryptorchidism 21/46 (45.7%) of males (john2023expandingthespeech pages 2-2) | St John et al. 2023, Eur J Hum Genet | https://doi.org/10.1038/s41431-022-01230-7 | 2023-12 |
| Phenotypes (EJHG speech cohort 2023) | Verbal status | 62/81 (76.5%) verbal; minimally verbal participants used AAC successfully (john2023expandingthespeech pages 1-2) | St John et al. 2023, Eur J Hum Genet | https://doi.org/10.1038/s41431-022-01230-7 | 2023-12 |
| Phenotypes (EJHG speech cohort 2023) | Motor speech disorders | Apraxia in 39/61 (63.9%) verbal participants; dysarthria in 28/61 (45.9%) (john2023expandingthespeech pages 1-2) | St John et al. 2023, Eur J Hum Genet | https://doi.org/10.1038/s41431-022-01230-7 | 2023-12 |
| Phenotypes (EJHG speech cohort 2023) | Stuttering | 36/47 (76.6%) of verbal participants; described as late-onset and fluctuating (john2023expandingthespeech pages 1-2) | St John et al. 2023, Eur J Hum Genet | https://doi.org/10.1038/s41431-022-01230-7 | 2023-12 |
| Diagnostics / omics | 2024 blood DNAm episignature cohort | Whole-blood DNAm profiled in 13 individuals with KANSL1 variants, 4 with 17q21.31 microdeletions, and 21 controls using Illumina EPIC array (awamleh2024anewblood pages 1-2) | Awamleh et al. 2024, Eur J Hum Genet | https://doi.org/10.1038/s41431-024-01538-6 | 2024-01 |
| Diagnostics / omics | 2024 episignature size | Robust blood DNA methylation signature of 456 significant CpG sites (awamleh2024anewblood pages 1-2, awamleh2024anewblood pages 2-3) | Awamleh et al. 2024, Eur J Hum Genet | https://doi.org/10.1038/s41431-024-01538-6 | 2024-01 |
| Diagnostics / omics | Discovery and validation | Discovery cohort n=8 KdVS cases; independent validation cohort n=8; validation SVM scores for KdVS cases 75–92% vs controls 0–13% (awamleh2024anewblood pages 5-7, awamleh2024anewblood pages 2-3, awamleh2024anewblood pages 7-8) | Awamleh et al. 2024, Eur J Hum Genet | https://doi.org/10.1038/s41431-024-01538-6 | 2024-01 |
| Diagnostics / omics | Variant classification utility | Used to classify 2 KANSL1 VUS and 4 atypical-presentation variants; one missense p.Thr887Met scored KdVS-like (~72%), while p.Gly900Glu scored control-like (~4.7%) (awamleh2024anewblood pages 3-5, awamleh2024anewblood pages 1-2, awamleh2024anewblood pages 7-8) | Awamleh et al. 2024, Eur J Hum Genet | https://doi.org/10.1038/s41431-024-01538-6 | 2024-01 |
| Diagnostics / omics | Microdeletion vs sequence variant DNAm difference | No significant DNAm difference between 17q21.31 microdeletion carriers and KANSL1 sequence-variant carriers (adjusted p = 0.34) (awamleh2024anewblood pages 2-3) | Awamleh et al. 2024, Eur J Hum Genet | https://doi.org/10.1038/s41431-024-01538-6 | 2024-01 |
Table: This table condenses the most actionable disease-level facts for Koolen-de Vries syndrome, including identifiers, causal genetics, prevalence, major 2023 cohort phenotype frequencies, and the 2024 DNA methylation episignature findings. It is useful as a quick-reference artifact for knowledge-base population and evidence-backed summarization.
References
(colin2023genidaaparticipatory pages 2-3): Florent Colin, Pauline Burger, Timothée Mazzucotelli, Axelle Strehle, Joost Kummeling, Nicole Collot, Elyette Broly, Angela T. Morgan, Kenneth A. Myers, Agnès Bloch-Zupan, Charlotte W. Ockeloen, Bert B.A. de Vries, Tjitske Kleefstra, Pierre Parrend, David A. Koolen, and Jean-Louis Mandel. Genida, a participatory patient registry for genetic forms of intellectual disability provides detailed caregiver-reported information on 237 individuals with koolen-de vries syndrome. Genetics in Medicine Open, 1:100817, Jan 2023. URL: https://doi.org/10.1016/j.gimo.2023.100817, doi:10.1016/j.gimo.2023.100817. This article has 9 citations and is from a peer-reviewed journal.
(houser2025neuroimagingofkoolende pages 2-8): Karis Houser, Sara C Esteves, and Michael S. Kuwabara. Neuroimaging of koolen-de vries syndrome: a rare genetic disorder. Cureus, Feb 2025. URL: https://doi.org/10.7759/cureus.79194, doi:10.7759/cureus.79194. This article has 1 citations.
(farne2022koolen‐devriessyndrome pages 10-12): Marianna Farnè, Laura Bernardini, Anna Capalbo, Giusy Cavarretta, Barbara Torres, Mariabeatrice Sanchini, Sergio Fini, Alessandra Ferlini, and Stefania Bigoni. Koolen‐de vries syndrome in a 63‐year‐old woman: report of the oldest patient and a review of the adult phenotype. American Journal of Medical Genetics. Part a, 188:692-707, Oct 2022. URL: https://doi.org/10.1002/ajmg.a.62536, doi:10.1002/ajmg.a.62536. This article has 10 citations and is from a peer-reviewed journal.
(colin2023genidaaparticipatory pages 3-4): Florent Colin, Pauline Burger, Timothée Mazzucotelli, Axelle Strehle, Joost Kummeling, Nicole Collot, Elyette Broly, Angela T. Morgan, Kenneth A. Myers, Agnès Bloch-Zupan, Charlotte W. Ockeloen, Bert B.A. de Vries, Tjitske Kleefstra, Pierre Parrend, David A. Koolen, and Jean-Louis Mandel. Genida, a participatory patient registry for genetic forms of intellectual disability provides detailed caregiver-reported information on 237 individuals with koolen-de vries syndrome. Genetics in Medicine Open, 1:100817, Jan 2023. URL: https://doi.org/10.1016/j.gimo.2023.100817, doi:10.1016/j.gimo.2023.100817. This article has 9 citations and is from a peer-reviewed journal.
(john2023expandingthespeech pages 2-2): Miya St John, Olivia van Reyk, David Koolen, Bert de Vries, David Amor, and Angela Morgan. Expanding the speech and language phenotype in koolen-de vries syndrome: late onset and periodic stuttering a novel feature. European Journal of Human Genetics, 31:531-540, Dec 2023. URL: https://doi.org/10.1038/s41431-022-01230-7, doi:10.1038/s41431-022-01230-7. This article has 18 citations and is from a domain leading peer-reviewed journal.
(li2022kansl1haploinsufficiencyimpairs pages 1-2): Tingting Li, Dingyi Lu, C. Yao, Tingting Li, Hua Dong, Zhanqi Li, Guang Xu, Jiayi Chen, Hao Zhang, Xiaoyu Yi, Haizhen Zhu, Guangqin Liu, Kaiqing Wen, Haixin Zhao, Jun Gao, Yakun Zhang, Qiu-Ying Han, Teng Li, Weina Zhang, Jie Zhao, Tao Li, Zhaofang Bai, Moshi Song, Xin Hua He, Tao Zhou, Qing Xia, Ai-ling Li, and Xin Pan. Kansl1 haploinsufficiency impairs autophagosome-lysosome fusion and links autophagic dysfunction with koolen-de vries syndrome in mice. Nature Communications, Feb 2022. URL: https://doi.org/10.1038/s41467-022-28613-0, doi:10.1038/s41467-022-28613-0. This article has 52 citations and is from a highest quality peer-reviewed journal.
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(saxena2021koolen‐devriessyndrome pages 2-4): Deepti Saxena, Amita Moirangthem, Arya Shambhavi, and Shubha R. Phadke. Koolen‐de vries syndrome: first report of two unrelated indian patients. American Journal of Medical Genetics Part A, 185:982-985, Dec 2021. URL: https://doi.org/10.1002/ajmg.a.62008, doi:10.1002/ajmg.a.62008. This article has 0 citations.
(john2023expandingthespeech pages 1-2): Miya St John, Olivia van Reyk, David Koolen, Bert de Vries, David Amor, and Angela Morgan. Expanding the speech and language phenotype in koolen-de vries syndrome: late onset and periodic stuttering a novel feature. European Journal of Human Genetics, 31:531-540, Dec 2023. URL: https://doi.org/10.1038/s41431-022-01230-7, doi:10.1038/s41431-022-01230-7. This article has 18 citations and is from a domain leading peer-reviewed journal.
(colin2023genidaaparticipatory pages 6-7): Florent Colin, Pauline Burger, Timothée Mazzucotelli, Axelle Strehle, Joost Kummeling, Nicole Collot, Elyette Broly, Angela T. Morgan, Kenneth A. Myers, Agnès Bloch-Zupan, Charlotte W. Ockeloen, Bert B.A. de Vries, Tjitske Kleefstra, Pierre Parrend, David A. Koolen, and Jean-Louis Mandel. Genida, a participatory patient registry for genetic forms of intellectual disability provides detailed caregiver-reported information on 237 individuals with koolen-de vries syndrome. Genetics in Medicine Open, 1:100817, Jan 2023. URL: https://doi.org/10.1016/j.gimo.2023.100817, doi:10.1016/j.gimo.2023.100817. This article has 9 citations and is from a peer-reviewed journal.
(colin2023genidaaparticipatory pages 7-9): Florent Colin, Pauline Burger, Timothée Mazzucotelli, Axelle Strehle, Joost Kummeling, Nicole Collot, Elyette Broly, Angela T. Morgan, Kenneth A. Myers, Agnès Bloch-Zupan, Charlotte W. Ockeloen, Bert B.A. de Vries, Tjitske Kleefstra, Pierre Parrend, David A. Koolen, and Jean-Louis Mandel. Genida, a participatory patient registry for genetic forms of intellectual disability provides detailed caregiver-reported information on 237 individuals with koolen-de vries syndrome. Genetics in Medicine Open, 1:100817, Jan 2023. URL: https://doi.org/10.1016/j.gimo.2023.100817, doi:10.1016/j.gimo.2023.100817. This article has 9 citations and is from a peer-reviewed journal.
(john2023expandingthespeech pages 3-4): Miya St John, Olivia van Reyk, David Koolen, Bert de Vries, David Amor, and Angela Morgan. Expanding the speech and language phenotype in koolen-de vries syndrome: late onset and periodic stuttering a novel feature. European Journal of Human Genetics, 31:531-540, Dec 2023. URL: https://doi.org/10.1038/s41431-022-01230-7, doi:10.1038/s41431-022-01230-7. This article has 18 citations and is from a domain leading peer-reviewed journal.
(awamleh2024anewblood pages 3-5): Zain Awamleh, Sanaa Choufani, Wendy Wu, Dmitrijs Rots, Alexander J. M. Dingemans, Nael Nadif Kasri, Susana Boronat, Salvador Ibañez-Mico, Laura Cuesta Herraiz, Irene Ferrer, Antonio Martínez Carrascal, Luis A. Pérez-Jurado, Gemma Aznar Lain, Juan Dario Ortigoza-Escobar, Bert B. A. de Vries, David A. Koolen, and Rosanna Weksberg. A new blood dna methylation signature for koolen-de vries syndrome: classification of missense kansl1 variants and comparison to fibroblast cells. European Journal of Human Genetics, 32:324-332, Jan 2024. URL: https://doi.org/10.1038/s41431-024-01538-6, doi:10.1038/s41431-024-01538-6. This article has 13 citations and is from a domain leading peer-reviewed journal.
(awamleh2024anewblood pages 1-2): Zain Awamleh, Sanaa Choufani, Wendy Wu, Dmitrijs Rots, Alexander J. M. Dingemans, Nael Nadif Kasri, Susana Boronat, Salvador Ibañez-Mico, Laura Cuesta Herraiz, Irene Ferrer, Antonio Martínez Carrascal, Luis A. Pérez-Jurado, Gemma Aznar Lain, Juan Dario Ortigoza-Escobar, Bert B. A. de Vries, David A. Koolen, and Rosanna Weksberg. A new blood dna methylation signature for koolen-de vries syndrome: classification of missense kansl1 variants and comparison to fibroblast cells. European Journal of Human Genetics, 32:324-332, Jan 2024. URL: https://doi.org/10.1038/s41431-024-01538-6, doi:10.1038/s41431-024-01538-6. This article has 13 citations and is from a domain leading peer-reviewed journal.
(awamleh2024anewblood pages 2-3): Zain Awamleh, Sanaa Choufani, Wendy Wu, Dmitrijs Rots, Alexander J. M. Dingemans, Nael Nadif Kasri, Susana Boronat, Salvador Ibañez-Mico, Laura Cuesta Herraiz, Irene Ferrer, Antonio Martínez Carrascal, Luis A. Pérez-Jurado, Gemma Aznar Lain, Juan Dario Ortigoza-Escobar, Bert B. A. de Vries, David A. Koolen, and Rosanna Weksberg. A new blood dna methylation signature for koolen-de vries syndrome: classification of missense kansl1 variants and comparison to fibroblast cells. European Journal of Human Genetics, 32:324-332, Jan 2024. URL: https://doi.org/10.1038/s41431-024-01538-6, doi:10.1038/s41431-024-01538-6. This article has 13 citations and is from a domain leading peer-reviewed journal.
(colin2023genidaaparticipatory pages 1-2): Florent Colin, Pauline Burger, Timothée Mazzucotelli, Axelle Strehle, Joost Kummeling, Nicole Collot, Elyette Broly, Angela T. Morgan, Kenneth A. Myers, Agnès Bloch-Zupan, Charlotte W. Ockeloen, Bert B.A. de Vries, Tjitske Kleefstra, Pierre Parrend, David A. Koolen, and Jean-Louis Mandel. Genida, a participatory patient registry for genetic forms of intellectual disability provides detailed caregiver-reported information on 237 individuals with koolen-de vries syndrome. Genetics in Medicine Open, 1:100817, Jan 2023. URL: https://doi.org/10.1016/j.gimo.2023.100817, doi:10.1016/j.gimo.2023.100817. This article has 9 citations and is from a peer-reviewed journal.
(prat2021ocularmanifestationsand pages 4-4): Daphna Prat, William R. Katowitz, Alanna Strong, and James A. Katowitz. Ocular manifestations and surgical interventions in pediatric patients with koolen-de-vries syndrome. Ophthalmic Genetics, 42:186-188, Jan 2021. URL: https://doi.org/10.1080/13816810.2020.1868012, doi:10.1080/13816810.2020.1868012. This article has 7 citations and is from a peer-reviewed journal.
(pfalzer2024koolendevriessyndrome pages 2-3): Anna C. Pfalzer, Blake Ivers, Alayna Haynam, Barbara Drake, David A. Koolen, Nael Nadif Kasri, Bert B. A. de Vries, Heather C. Mefford, Angela Morgan, Terry Jo Bichell, Elijah Simon, Ananya Terala, Kenneth A. Myers, and Ashley Point. Koolen-de vries syndrome: a journey from diagnosis to treatments. Therapeutic Advances in Rare Disease, Jan 2024. URL: https://doi.org/10.1177/26330040241265414, doi:10.1177/26330040241265414. This article has 1 citations.
(awamleh2024anewblood pages 5-7): Zain Awamleh, Sanaa Choufani, Wendy Wu, Dmitrijs Rots, Alexander J. M. Dingemans, Nael Nadif Kasri, Susana Boronat, Salvador Ibañez-Mico, Laura Cuesta Herraiz, Irene Ferrer, Antonio Martínez Carrascal, Luis A. Pérez-Jurado, Gemma Aznar Lain, Juan Dario Ortigoza-Escobar, Bert B. A. de Vries, David A. Koolen, and Rosanna Weksberg. A new blood dna methylation signature for koolen-de vries syndrome: classification of missense kansl1 variants and comparison to fibroblast cells. European Journal of Human Genetics, 32:324-332, Jan 2024. URL: https://doi.org/10.1038/s41431-024-01538-6, doi:10.1038/s41431-024-01538-6. This article has 13 citations and is from a domain leading peer-reviewed journal.
(awamleh2024anewblood pages 7-8): Zain Awamleh, Sanaa Choufani, Wendy Wu, Dmitrijs Rots, Alexander J. M. Dingemans, Nael Nadif Kasri, Susana Boronat, Salvador Ibañez-Mico, Laura Cuesta Herraiz, Irene Ferrer, Antonio Martínez Carrascal, Luis A. Pérez-Jurado, Gemma Aznar Lain, Juan Dario Ortigoza-Escobar, Bert B. A. de Vries, David A. Koolen, and Rosanna Weksberg. A new blood dna methylation signature for koolen-de vries syndrome: classification of missense kansl1 variants and comparison to fibroblast cells. European Journal of Human Genetics, 32:324-332, Jan 2024. URL: https://doi.org/10.1038/s41431-024-01538-6, doi:10.1038/s41431-024-01538-6. This article has 13 citations and is from a domain leading peer-reviewed journal.