FG Syndrome 1: Disease-Characteristics Research Report

Executive summary and scope

FG syndrome 1 (FGS1) is the molecularly defined, X-linked multiple-congenital-anomaly/neurodevelopmental disorder classically called Opitz–Kaveggia syndrome, caused by the recurrent germline MED12 c.2881C>T (p.Arg961Trp; p.R961W) variant. It must be distinguished from the older, phenotype-based label “FG syndrome,” which includes genetically heterogeneous and MED12-negative cases. Only about 3% of patients historically assigned a clinical FG-syndrome diagnosis were found to carry p.Arg961Trp in one diagnostic series. The principal evidence base remains a small cohort—23 molecularly confirmed males from 10 families—so frequencies below are descriptive, not population estimates. (clark2009fgsyndromean pages 1-2, clark2009fgsyndromean pages 7-7, clark2009fgsyndromean pages 4-6)

No substantial FGS1-specific clinical or therapeutic advances were identified from 2023–2024. Recent work on MED12 has primarily refined the wider allelic spectrum and mechanisms of Mediator-complex dysfunction rather than changing FGS1 diagnosis or care. The most relevant modern synthesis is van de Plassche and de Brouwer, published April 2021, DOI: 10.3390/genes12050663. Its abstract states: “Missense variants in MED12 cause FG syndrome, Lujan-Fryns syndrome, and Ohdo syndrome, as well as non-syndromic intellectual disability (ID) in hemizygous males.” This statement concerns the broader MED12 spectrum; the classic FGS1 diagnosis is specifically anchored to p.Arg961Trp. (graham2013med12relateddisorders pages 1-2, plassche2021med12related(neuro)developmentaldisorders pages 7-10)

Table: This table summarizes the most actionable evidence for molecularly confirmed FG syndrome 1, including defining variant, cohort size, major phenotype frequencies, mechanism, diagnostic performance, prognosis, and treatment gaps. It is useful for separating MED12 p.Arg961Trp-associated disease from the broader heterogeneous FG phenotype.

1. Disease information

Definition and history

FGS1 is a congenital, lifelong Mendelian disorder characterized by developmental delay/intellectual disability, congenital hypotonia, severe constipation or anorectal abnormalities, characteristic craniofacial morphology and behavior, and variable brain, cardiac, skeletal, ocular, and genitourinary anomalies. Opitz and Kaveggia originally described five affected males—three brothers and two male first cousins—in 1974. The causal recurrent MED12 variant was established in 2007. (clark2009fgsyndromean pages 1-2, graham2013med12relateddisorders pages 1-2)

Identifiers and synonyms

• OMIM: 305450, FG syndrome 1/Opitz–Kaveggia syndrome.
• Causal gene: MED12, OMIM 300188, Xq13.
• Synonyms: FG syndrome type 1; FGS1; Opitz–Kaveggia syndrome; FG syndrome, MED12-related.
• MONDO: A dedicated current MONDO identifier could not be verified from the retrieved primary literature; a knowledge-base ingest should resolve the live MONDO release rather than infer an identifier.
• Orphanet: A current subtype-specific number was not verified in the retrieved evidence.
• ICD-10/ICD-11 and MeSH: No specific FGS1 code was established. Cases are generally represented under broader congenital-malformation, syndromic intellectual-disability, or rare genetic-disease categories.

The evidence summarized here is aggregated disease-level literature, mostly pedigrees, dysmorphology examinations, records, imaging, and patient-derived cell experiments—not individual EHR data.

2. Etiology

Cause and genetic risk

FGS1 is caused by the germline hemizygous MED12 NM_005120.3:c.2881C>T, p.(Arg961Trp) missense variant in affected males. It is an X-linked disorder: transmission through heterozygous females produces at-risk sons, while male-to-male transmission does not occur. No environmental, infectious, lifestyle, occupational, or toxic cause has been demonstrated. (clark2009fgsyndromean pages 6-7, clark2009fgsyndromean pages 7-7, graham2013med12relateddisorders pages 1-2)

The core cohort found clinically unaffected, intellectually normal heterozygous females. This supports sex-dependent expression, probably influenced by X-inactivation, but does not establish a numerical penetrance estimate for every carrier population. Expressivity among affected males is variable, particularly for congenital malformations and intellectual severity. No validated modifier gene, protective allele, founder haplotype, anticipation, or reproducible germline-mosaicism rate has been defined. (clark2009fgsyndromean pages 6-7)

Protective factors and gene–environment interaction

No genetic or environmental factor is known to prevent expression in a hemizygous male. No reproducible gene–environment interaction has been reported. Good nutrition, early therapy, constipation control, and treatment of cardiac or feeding complications can reduce secondary morbidity but are not etiologic protection.

3. Phenotypes

The best quantitative data derive from incompletely assessed subsets of 23 confirmed males; denominators therefore vary. (clark2009fgsyndromean pages 4-6, clark2009fgsyndromean pages 6-7)

Characteristic facies, affable behavior, and infantile hypotonia/feeding difficulty/constipation were each reported in all 13 subjects in one deeply characterized subset; congenital anomalies occurred in 11/13. These figures are vulnerable to referral and publication bias. (clark2009fgsyndromean pages 2-3, clark2009fgsyndromean pages 3-4)

Quality-of-life studies using EQ-5D, SF-36, PROMIS, or an FGS1-specific instrument were not found. Major burdens are communication impairment, dependence in daily living, chronic bowel dysfunction, anxiety with transitions, mobility limitations, feeding problems, sleep disturbance, and consequences of congenital anomalies. Socialization may be a relative strength. (graham2013med12relateddisorders pages 2-3)

4. Genetic and molecular information

• Gene: MED12, mediator complex subunit 12; Xq13; HGNC symbol MED12.
• Defining FGS1 variant: c.2881C>T, p.Arg961Trp, missense; germline and hemizygous in affected males.
• Population frequency: No numerical gnomAD frequency was established in the retrieved evidence. Its recurrence in affected pedigrees, segregation, rarity, and functional evidence support pathogenicity; a current clinical report should query the live gnomAD and ClinVar releases.
• Functional class: Not simple whole-gene loss of function. Evidence favors a pathway-selective altered-function/hypomorphic transcriptional-regulatory defect. Complete MED12 loss has broader and often developmentally severe consequences. (plassche2021med12related(neuro)developmentaldisorders pages 7-10, plassche2021med12related(neuro)developmentaldisorders pages 6-7)

Other MED12 variants cause different allelic disorders, including Lujan syndrome—classically p.Asn1007Ser—X-linked Ohdo syndrome and broader male or female neurodevelopmental phenotypes. Protein-truncating MED12 variants in females can cause Hardikar syndrome or other severe syndromic presentations and should not automatically be called FGS1. (graham2013med12relateddisorders pages 1-2, plassche2021med12related(neuro)developmentaldisorders pages 7-10)

No validated FGS1 modifier gene or disease-specific epigenetic signature is known. Large deletions, duplications, translocations, aneuploidy, repeat expansions, mitochondrial variants, and somatic MED12 mutations are not the defining cause of FGS1.

5. Environmental information

Environmental toxins, radiation, pollution, diet, smoking, alcohol, exercise, occupational exposures, and infectious agents have no established causal role. Environmental care affects complications: inadequate hydration or mobility can worsen constipation, and poorly structured transitions may exacerbate anxiety and behavior. These are management interactions, not demonstrated etiologic gene–environment effects. FGS1 is neither infectious nor zoonotic.

6. Mechanism and pathophysiology

Upstream molecular defect

MED12 is part of the Mediator kinase module and helps couple transcription factors and regulatory signals to RNA polymerase II. p.Arg961Trp does not appear to abolish all MED12 functions; it selectively impairs recruitment or response at particular regulatory complexes. MED12 loss can reduce super-enhancer capacity by approximately 50% and disturb enhancer–promoter interactions, although these broader loss experiments are not equivalent to FGS1. (plassche2021med12related(neuro)developmentaldisorders pages 7-10, plassche2021med12related(neuro)developmentaldisorders pages 6-7)

Supported pathway effects

1. Immediate-early genes and Pol II recruitment—human patient cells. In EBV-immortalized lymphoblastoid cells from p.Arg961Trp patients, JUN was downregulated and FOS upregulated. Chromatin immunoprecipitation showed that MED12 and RNA polymerase II promoter recruitment tracked these changes; impaired TCF4 recruitment was observed at JUN, while altered ELK-factor occupancy occurred at FOS. This supports stimulus-responsive transcriptional dysregulation. DOI: 10.1093/hmg/ddx099, published June 2017. (donnio2017med12relatedxliddisorders pages 10-14)

2. SHH–GLI3 signaling—patient cells and rescue experiments. MED12 normally constrains GLI3-dependent Sonic Hedgehog transcription. Patient lymphoblast lines carrying MED12 XLID variants, including p.Arg961Trp, had increased transcripts of GLI3-regulated targets including CREB5, BMP4, and NEUROG2. p.Arg961Trp failed to restore normal SHH inhibition in a MED12-null experimental setting and showed reduced CDK8 recruitment at GLI3 sites while retaining recruitment at unrelated PPARγ targets. DOI: 10.1002/mgg3.569, published February 2019. (srivastava2019dysregulationsofsonic pages 8-9, plassche2021med12related(neuro)developmentaldisorders pages 7-10, srivastava2019dysregulationsofsonic pages 1-2)

3. REST/neural-gene repression. Experimental rescue studies indicate that p.Arg961Trp fails to restore REST-mediated silencing while retaining β-catenin rescue capacity. Unscheduled derepression of neural genes could disrupt neuronal differentiation. This effect appears kinase-independent and therefore differs mechanistically from the CDK8-dependent SHH defect. (plassche2021med12related(neuro)developmentaldisorders pages 6-7)

Proposed causal chain

Germline MED12 p.Arg961Trp → selective disruption of signal-responsive Mediator assembly/recruitment → altered Pol II occupancy, immediate-early-gene expression, REST repression, and SHH/GLI3 developmental transcription → abnormal neurodevelopment and morphogenesis → intellectual disability, hypotonia, corpus-callosum, craniofacial, anorectal, cardiac, and skeletal phenotypes. The downstream organ links are biologically plausible but not proven directly in fetal human brain, enteric nervous system, heart, or anorectal tissue.

Suggested annotations include GO:0016592 mediator complex; GO:0006357 regulation of transcription by RNA polymerase II; GO:0007224 smoothened signaling pathway; GO:0045664 regulation of neuron differentiation; GO:0007417 central nervous system development; GO:0060536 cartilage morphogenesis. Candidate cell types—not demonstrated selective targets—include neural progenitor cell (CL:0011020), neuron (CL:0000540), enteric neuron (CL:0007011), cardiomyocyte (CL:0000746), and chondrocyte (CL:0000138).

No FGS1-specific single-cell, spatial-transcriptomic, proteomic, metabolomic, lipidomic, or multi-omic human-tissue dataset was identified. No characteristic immune, inflammatory, metabolic, mitochondrial, aggregation, fibrosis, or tissue-necrosis mechanism has been demonstrated.

7. Anatomical structures affected

• Nervous system: cerebral commissures, especially corpus callosum; pituitary/sella and optic nerve can be abnormal. Suggested UBERON: UBERON:0002336 corpus callosum, UBERON:0000007 pituitary gland, UBERON:0000966 retina, UBERON:0001908 optic nerve.
• Digestive/anorectal system: anus, distal bowel, and functional intestinal motility; UBERON: UBERON:0001245 anus, UBERON:0000160 intestine, UBERON:0001988 rectum.
• Cardiovascular: congenital structural heart disease; UBERON:0000948 heart.
• Musculoskeletal: skull, vertebrae/ribs, chest wall, joints, hips, hands/thumbs; UBERON:0003129 skull, UBERON:0002416 vertebral column, UBERON:0001464 hand.
• Craniofacial and ear structures: face and external ear; UBERON:0001456 face, UBERON:0003102 external ear.

The relevant subcellular site is principally the nucleus and chromatin-associated Mediator/transcription machinery: GO:0005634 nucleus, GO:0000785 chromatin, GO:0016592 mediator complex. No characteristic lateralization has been reported. (clark2009fgsyndromean pages 4-6, clark2009fgsyndromean pages 6-7)

8. Temporal development

FGS1 begins prenatally as a developmental disorder. Hypotonia, feeding problems, constipation, dysmorphism, cardiac disease, and anorectal malformations may be apparent neonatally; developmental and behavioral differences emerge during infancy and childhood. Facial recognition may be easiest in early childhood. (clark2009fgsyndromean pages 4-6, clark2009fgsyndromean pages 6-7)

The course is chronic and lifelong, not episodic or relapsing-remitting. Congenital malformations are structurally stable unless corrected; hypotonia often improves with age, while intellectual, speech, and adaptive limitations persist. No formal stages, progression rate, remission pattern, or validated critical therapeutic window has been defined, although early feeding, cardiac, bowel, developmental, speech, and vision intervention is clinically important. Some children achieve walking only in later childhood, while surviving adults can function into their fifth or sixth decades. (clark2009fgsyndromean pages 6-7, clark2009fgsyndromean pages 3-4)

9. Inheritance and population

Inheritance is X-linked. A heterozygous carrier has a 50% probability of transmitting the variant in each pregnancy; a son inheriting it is expected to be affected, whereas a daughter inheriting it is generally an asymptomatic carrier based on the core pedigrees. An affected male transmits the variant to all daughters and no sons, assuming reproductive fitness. This is standard X-linked counseling and should be individualized for maternal mosaicism and X-inactivation.

Formal incidence, prevalence per 100,000, carrier frequency, ethnic enrichment, geographic concentration, and sex ratio from a registry are unavailable. FGS1 is ultra-rare and reported across unrelated families. The clinical cohort consists almost entirely of males because of X-linked hemizygous expression. No founder effect, consanguinity association, anticipation, or population-specific risk has been established. Early family histories often included deceased male infants, miscarriages, or X-linked intellectual disability. (clark2009fgsyndromean pages 6-7, clark2009fgsyndromean pages 1-2)

10. Diagnostics

Recommended approach

Diagnosis requires a compatible phenotype plus identification of a pathogenic MED12 variant, with p.Arg961Trp defining classic FGS1. Modern testing should use an intellectual-disability/congenital-anomaly panel containing MED12 or exome/genome sequencing, with confirmation and segregation testing. Targeted testing for c.2881C>T is efficient where the classic phenotype or familial variant is known. A historical phenotype algorithm achieved 100% sensitivity and approximately 90% specificity and reduced targeted testing by 74%, but it was derived from small retrospective cohorts and should not replace contemporary sequencing. (clark2009fgsyndromean pages 1-2, clark2009fgsyndromean pages 2-3)

WES/WGS is useful for atypical cases and for detecting alternative diagnoses. Copy-number analysis should be considered when sequencing is negative or the phenotype suggests a genomic disorder. Karyotyping, FISH, mitochondrial sequencing, repeat-expansion tests, biopsy, metabolomics, and liquid biopsy are not routine FGS1 tests.

Baseline clinical evaluation

Recommended assessments include developmental and neurologic examination; brain MRI with attention to the corpus callosum; echocardiography and ECG; formal ophthalmology; hearing evaluation; feeding/swallow and nutritional assessment; gastrointestinal/anorectal examination; renal/genitourinary evaluation when indicated; and orthopedic review. Routine blood or urine chemistry has no diagnostic biomarker. (clark2009fgsyndromean pages 4-6, clark2009fgsyndromean pages 6-7)

Differential diagnosis

Important differentials include Lujan syndrome and X-linked Ohdo syndrome caused by other MED12 variants; broader MED12-related neurodevelopmental disorders; FLNA-, UPF3B-, and BRWD3-associated X-linked intellectual disability; Xq28 duplication syndromes; fragile X syndrome; Mowat–Wilson syndrome; Coffin–Siris spectrum; and other syndromic causes of hypotonia, constipation, macrocephaly, callosal abnormality, and anal or cardiac malformations. A MED12-negative patient with nonspecific “FG-like” findings should not automatically retain an FGS1 label. (clark2009fgsyndromean pages 7-7, graham2013med12relateddisorders pages 2-3, graham2013med12relateddisorders pages 1-2)

There is no population newborn screen. Cascade testing of relatives is appropriate after molecular confirmation.

11. Outcome and prognosis

Early mortality occurred in 8 of the 10 reported families, although the literature does not provide a reliable disease-specific mortality rate or survival curve. Congenital cardiac, respiratory, feeding, and gastrointestinal complications likely contribute, but causes cannot be assigned uniformly. Among survivors beyond infancy, mortality did not appear markedly elevated in the small series, and three males were reportedly functioning into their fifth or sixth decades. (clark2009fgsyndromean pages 6-7)

Long-term morbidity includes intellectual and speech disability, chronic constipation, anxiety/behavioral dysregulation, sleep disturbance, orthopedic problems, and residual consequences of congenital anomalies. Recovery from the underlying disorder is not expected, but hypotonia, mobility, communication, comfort, and participation may improve. No validated molecular prognostic biomarker or FGS1-specific quality-of-life statistic exists.

12. Treatment

There is no disease-modifying, gene, RNA, cell, targeted, or approved MED12-directed therapy for FGS1. No FGS1-specific interventional clinical trial or treatment-response rate was identified. Care is individualized and multidisciplinary. (graham2013med12relateddisorders pages 2-3, clark2009fgsyndromean pages 6-7)

• Feeding therapy, nutritional support, and gastrostomy when required — suggested MAXO:0001006 nutritional therapy, MAXO:0001175 gastrostomy.
• Aggressive constipation management, reflux treatment, and evaluation for structural anorectal disease; surgery where indicated — MAXO:0000088 surgical procedure, MAXO:0000011 therapeutic procedure.
• Cardiology surveillance and repair of significant congenital defects — MAXO:0000487 echocardiography, surgical-procedure terms as appropriate.
• Physical and occupational therapy for hypotonia, mobility, contractures, and adaptive skills — MAXO:0000015 physical therapy, MAXO:0000017 occupational therapy.
• Early, sustained speech-language and augmentative-communication support — MAXO:0000018 speech therapy.
• Structured routines, advance warnings for transitions, educational support, and behavioral/psychological treatment for anxiety, attention problems, or sleep disturbance.
• Ophthalmic, hearing, orthopedic, neurologic, dental, and genitourinary treatment according to findings.

Reported real-world interventions include tube feeding, gastrostomy, fundoplication, congenital-heart surgery, orthopedic management, and developmental therapies. Pharmacotherapy is symptom-directed; no FGS1 pharmacogenomic guidance or evidence-based combination regimen exists. (graham2013med12relateddisorders pages 2-3, clark2009fgsyndromean pages 3-4)

13. Prevention

The inherited molecular defect cannot be prevented by diet, vaccination, lifestyle change, or environmental avoidance. Primary reproductive prevention options after identification of a familial variant include genetic counseling, carrier testing, preimplantation genetic testing, chorionic-villus sampling, amniocentesis, and use of donor gametes. Secondary prevention consists of early molecular diagnosis and prompt detection of cardiac, feeding, bowel, visual, hearing, and developmental complications. Tertiary prevention includes bowel regimens, nutrition, rehabilitation, communication support, safety planning, and surveillance for known congenital anomalies. No vaccine, preventive medication, public-health exposure intervention, or population screening program is applicable.

14. Other species and natural disease

MED12 is evolutionarily conserved in vertebrates, but no naturally occurring veterinary disorder established as an exact orthologue of human MED12 p.Arg961Trp FGS1 was identified. Consequently, no breed, VBO term, animal incidence, veterinary transmission, or zoonotic potential applies. Orthologues include Med12 in mouse (Mus musculus, NCBI Taxonomy 10090) and med12 in zebrafish (Danio rerio, Taxonomy 7955); exact live NCBI Gene IDs should be resolved during database ingestion.

15. Model organisms and experimental systems

The strongest FGS1-specific functional evidence comes from patient-derived EBV-immortalized lymphoblastoid cells, promoter ChIP/qPCR, and MED12-null/rescue cellular experiments. These models demonstrate altered JUN/FOS regulation, Pol II/MED12 recruitment, REST silencing, and SHH/GLI3 target expression. Their major limitation is that lymphoblasts do not model developing cortical neurons, enteric neurons, cardiomyocytes, or anorectal mesenchyme. (plassche2021med12related(neuro)developmentaldisorders pages 7-10, plassche2021med12related(neuro)developmentaldisorders pages 6-7, srivastava2019dysregulationsofsonic pages 1-2, donnio2017med12relatedxliddisorders pages 10-14)

Conditional and reduced-expression Med12 mouse models establish that MED12 is essential for embryogenesis and tissue development, but constitutive loss is often embryonic lethal and is not equivalent to the selective p.Arg961Trp disorder. A validated knock-in model shown to reproduce the complete human FGS1 phenotype was not identified in the retrieved evidence. No established FGS1 zebrafish, Drosophila, C. elegans, organoid, or patient-iPSC neuronal model with comprehensive phenotypic validation was found. Experts have proposed isogenic induced-neuron models to distinguish pathogenic MED12-specific expression signatures, underscoring that this remains a research need rather than a clinical assay. (plassche2021med12related(neuro)developmentaldisorders pages 7-10, plassche2021med12related(neuro)developmentaldisorders pages 6-7)

Evidence limitations and current expert assessment

The defining clinical dataset is small, familial, retrospective, and enriched for recognizable severe cases. Frequencies should therefore retain their original denominators and should not be interpreted as penetrance estimates. Mechanistic studies consistently indicate selective transcriptional-network dysfunction, but most were performed in lymphoblastoid or engineered cells rather than affected fetal tissues. As of the searched 2023–2024 literature, no prospective natural-history registry, standardized patient-reported outcome, validated biomarker, disease-modifying therapy, or FGS1-specific intervention trial was evident. The immediate priorities are longitudinal natural-history collection, modern variant curation, patient-derived neural and enteric models, and tissue-relevant multi-omic analysis.

Principal sources

1. Clark RD et al. FG syndrome, an X-linked multiple congenital anomaly syndrome: the clinical phenotype and an algorithm for diagnostic testing. Genetics in Medicine, published November 2009. DOI: 10.1097/GIM.0b013e3181bd3d90. (clark2009fgsyndromean pages 6-7, clark2009fgsyndromean pages 1-2)
2. Graham JM, Schwartz CE. MED12 related disorders. American Journal of Medical Genetics Part A, published November 2013. DOI: 10.1002/ajmg.a.36183. (graham2013med12relateddisorders pages 2-3, graham2013med12relateddisorders pages 1-2)
3. Donnio LM et al. MED12-related XLID disorders are dose-dependent of immediate early genes (IEGs) expression. Human Molecular Genetics, published June 2017. DOI: 10.1093/hmg/ddx099. (donnio2017med12relatedxliddisorders pages 10-14)
4. Srivastava S et al. Dysregulations of sonic hedgehog signaling in MED12-related X-linked intellectual disability disorders. Molecular Genetics & Genomic Medicine, published February 2019. DOI: 10.1002/mgg3.569. (srivastava2019dysregulationsofsonic pages 8-9, srivastava2019dysregulationsofsonic pages 1-2)
5. van de Plassche SR, de Brouwer APM. MED12-Related (Neuro)Developmental Disorders: A Question of Causality. Genes, published April 2021. DOI: 10.3390/genes12050663. (plassche2021med12related(neuro)developmentaldisorders pages 7-10, plassche2021med12related(neuro)developmentaldisorders pages 6-7)

References

1. (clark2009fgsyndromean pages 1-2): Robin Dawn Clark, John M. Graham, Michael J. Friez, Joe J. Hoo, Kenneth Lyons Jones, Carole McKeown, John B. Moeschler, F. Lucy Raymond, R. Curtis Rogers, Charles E. Schwartz, Agatino Battaglia, Michael J. Lyons, and Roger E. Stevenson. Fg syndrome, an x-linked multiple congenital anomaly syndrome: the clinical phenotype and an algorithm for diagnostic testing. Genetics in Medicine, 11:769-775, Nov 2009. URL: https://doi.org/10.1097/gim.0b013e3181bd3d90, doi:10.1097/gim.0b013e3181bd3d90. This article has 49 citations and is from a highest quality peer-reviewed journal.

2. (clark2009fgsyndromean pages 7-7): Robin Dawn Clark, John M. Graham, Michael J. Friez, Joe J. Hoo, Kenneth Lyons Jones, Carole McKeown, John B. Moeschler, F. Lucy Raymond, R. Curtis Rogers, Charles E. Schwartz, Agatino Battaglia, Michael J. Lyons, and Roger E. Stevenson. Fg syndrome, an x-linked multiple congenital anomaly syndrome: the clinical phenotype and an algorithm for diagnostic testing. Genetics in Medicine, 11:769-775, Nov 2009. URL: https://doi.org/10.1097/gim.0b013e3181bd3d90, doi:10.1097/gim.0b013e3181bd3d90. This article has 49 citations and is from a highest quality peer-reviewed journal.

3. (clark2009fgsyndromean pages 4-6): Robin Dawn Clark, John M. Graham, Michael J. Friez, Joe J. Hoo, Kenneth Lyons Jones, Carole McKeown, John B. Moeschler, F. Lucy Raymond, R. Curtis Rogers, Charles E. Schwartz, Agatino Battaglia, Michael J. Lyons, and Roger E. Stevenson. Fg syndrome, an x-linked multiple congenital anomaly syndrome: the clinical phenotype and an algorithm for diagnostic testing. Genetics in Medicine, 11:769-775, Nov 2009. URL: https://doi.org/10.1097/gim.0b013e3181bd3d90, doi:10.1097/gim.0b013e3181bd3d90. This article has 49 citations and is from a highest quality peer-reviewed journal.

4. (graham2013med12relateddisorders pages 1-2): John M. Graham and Charles E. Schwartz. Med12 related disorders. American Journal of Medical Genetics Part A, 161:2734-2740, Nov 2013. URL: https://doi.org/10.1002/ajmg.a.36183, doi:10.1002/ajmg.a.36183. This article has 97 citations.

5. (plassche2021med12related(neuro)developmentaldisorders pages 7-10): Stijn R. van de Plassche and Arjan P. M. de Brouwer. Med12-related (neuro)developmental disorders: a question of causality. Genes, 12 5:663, Apr 2021. URL: https://doi.org/10.3390/genes12050663, doi:10.3390/genes12050663. This article has 28 citations.

6. (graham2013med12relateddisorders pages 2-3): John M. Graham and Charles E. Schwartz. Med12 related disorders. American Journal of Medical Genetics Part A, 161:2734-2740, Nov 2013. URL: https://doi.org/10.1002/ajmg.a.36183, doi:10.1002/ajmg.a.36183. This article has 97 citations.

7. (clark2009fgsyndromean pages 6-7): Robin Dawn Clark, John M. Graham, Michael J. Friez, Joe J. Hoo, Kenneth Lyons Jones, Carole McKeown, John B. Moeschler, F. Lucy Raymond, R. Curtis Rogers, Charles E. Schwartz, Agatino Battaglia, Michael J. Lyons, and Roger E. Stevenson. Fg syndrome, an x-linked multiple congenital anomaly syndrome: the clinical phenotype and an algorithm for diagnostic testing. Genetics in Medicine, 11:769-775, Nov 2009. URL: https://doi.org/10.1097/gim.0b013e3181bd3d90, doi:10.1097/gim.0b013e3181bd3d90. This article has 49 citations and is from a highest quality peer-reviewed journal.

8. (clark2009fgsyndromean pages 2-3): Robin Dawn Clark, John M. Graham, Michael J. Friez, Joe J. Hoo, Kenneth Lyons Jones, Carole McKeown, John B. Moeschler, F. Lucy Raymond, R. Curtis Rogers, Charles E. Schwartz, Agatino Battaglia, Michael J. Lyons, and Roger E. Stevenson. Fg syndrome, an x-linked multiple congenital anomaly syndrome: the clinical phenotype and an algorithm for diagnostic testing. Genetics in Medicine, 11:769-775, Nov 2009. URL: https://doi.org/10.1097/gim.0b013e3181bd3d90, doi:10.1097/gim.0b013e3181bd3d90. This article has 49 citations and is from a highest quality peer-reviewed journal.

9. (donnio2017med12relatedxliddisorders pages 10-14): Lise-Marie Donnio, Baptiste Bidon, Satoru Hashimoto, Melanie May, Alexey Epanchintsev, Colm Ryan, William Allen, Anna Hackett, Jozef Gecz, Cindy Skinner, Roger E. Stevenson, Arjan P.M. de Brouwer, Charles Coutton, Christine Francannet, Pierre-Simon Jouk, Charles E. Schwartz, and Jean-Marc Egly. Med12-related xlid disorders are dose-dependent of immediate early genes (iegs) expression. Human Molecular Genetics, 26:2062–2075, Jun 2017. URL: https://doi.org/10.1093/hmg/ddx099, doi:10.1093/hmg/ddx099. This article has 33 citations and is from a domain leading peer-reviewed journal.

10. (srivastava2019dysregulationsofsonic pages 1-2): Siddharth Srivastava, Tejasvi Niranjan, Melanie M. May, Patrick Tarpey, William Allen, Anna Hackett, Pierre‐Simon Jouk, Lucy Raymond, Slyvain Briault, Cindy Skinner, Annick Toutain, Jozef Gecz, William Heath, Roger E. Stevenson, Charles E. Schwartz, and Tao Wang. Dysregulations of sonic hedgehog signaling in med12‐related x‐linked intellectual disability disorders. Molecular Genetics & Genomic Medicine, Feb 2019. URL: https://doi.org/10.1002/mgg3.569, doi:10.1002/mgg3.569. This article has 21 citations and is from a peer-reviewed journal.

11. (plassche2021med12related(neuro)developmentaldisorders pages 6-7): Stijn R. van de Plassche and Arjan P. M. de Brouwer. Med12-related (neuro)developmental disorders: a question of causality. Genes, 12 5:663, Apr 2021. URL: https://doi.org/10.3390/genes12050663, doi:10.3390/genes12050663. This article has 28 citations.

12. (clark2009fgsyndromean pages 3-4): Robin Dawn Clark, John M. Graham, Michael J. Friez, Joe J. Hoo, Kenneth Lyons Jones, Carole McKeown, John B. Moeschler, F. Lucy Raymond, R. Curtis Rogers, Charles E. Schwartz, Agatino Battaglia, Michael J. Lyons, and Roger E. Stevenson. Fg syndrome, an x-linked multiple congenital anomaly syndrome: the clinical phenotype and an algorithm for diagnostic testing. Genetics in Medicine, 11:769-775, Nov 2009. URL: https://doi.org/10.1097/gim.0b013e3181bd3d90, doi:10.1097/gim.0b013e3181bd3d90. This article has 49 citations and is from a highest quality peer-reviewed journal.

13. (srivastava2019dysregulationsofsonic pages 8-9): Siddharth Srivastava, Tejasvi Niranjan, Melanie M. May, Patrick Tarpey, William Allen, Anna Hackett, Pierre‐Simon Jouk, Lucy Raymond, Slyvain Briault, Cindy Skinner, Annick Toutain, Jozef Gecz, William Heath, Roger E. Stevenson, Charles E. Schwartz, and Tao Wang. Dysregulations of sonic hedgehog signaling in med12‐related x‐linked intellectual disability disorders. Molecular Genetics & Genomic Medicine, Feb 2019. URL: https://doi.org/10.1002/mgg3.569, doi:10.1002/mgg3.569. This article has 21 citations and is from a peer-reviewed journal.

Artifacts

• Edison artifact artifact-00