FOXG1 variants can be associated with milder phenotypes than congenital Rett syndrome with unassisted walking and language development.
FOXG1 gene
FOXG1 phenotype spectrum
congenital Rett syndrome
mild phenotype
Journal
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
ISSN: 1552-485X
Titre abrégé: Am J Med Genet B Neuropsychiatr Genet
Pays: United States
ID NLM: 101235742
Informations de publication
Date de publication:
08 Mar 2024
08 Mar 2024
Historique:
revised:
22
01
2024
received:
07
09
2023
accepted:
30
01
2024
medline:
9
3
2024
pubmed:
9
3
2024
entrez:
8
3
2024
Statut:
aheadofprint
Résumé
Since 2008, FOXG1 haploinsufficiency has been linked to a severe neurodevelopmental phenotype resembling Rett syndrome but with earlier onset. Most patients are unable to sit, walk, or speak. For years, FOXG1 sequencing was only prescribed in such severe cases, limiting insight into the full clinical spectrum associated with this gene. Next-generation sequencing (NGS) now enables unbiased diagnostics. Through the European Reference Network for Rare Malformation Syndromes, Intellectual and Other Neurodevelopmental Disorders, we gathered data from patients with heterozygous FOXG1 variants presenting a mild phenotype, defined as able to speak and walk independently. We also reviewed data from three previously reported patients meeting our criteria. We identified five new patients with pathogenic FOXG1 missense variants, primarily in the forkhead domain, showing varying nonspecific intellectual disability and developmental delay. These features are not typical of congenital Rett syndrome and were rarely associated with microcephaly and epilepsy. Our findings are consistent with a previous genotype-phenotype analysis by Mitter et al. suggesting the delineation of five different FOXG1 genotype groups. Milder phenotypes were associated with missense variants in the forkhead domain. This information may facilitate prognostic assessments in children carrying a FOXG1 variant and improve the interpretation of new variants identified with genomic sequencing.
Identifiants
pubmed: 38459409
doi: 10.1002/ajmg.b.32970
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e32970Subventions
Organisme : Dijon University Hospital
Organisme : European Regional Development Fund
Organisme : Ricerca Corrente 5X1000
Informations de copyright
© 2024 Wiley Periodicals LLC.
Références
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