FOXG1 variants can be associated with milder phenotypes than congenital Rett syndrome with unassisted walking and language development.
Fiche publication
Date publication
mars 2024
Journal
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FAIVRE Laurence, Pr PHILIPPE Christophe, Mr DUFFOURD Yannis, Pr THAUVIN-ROBINET Christel, Dr MAZEL Benoît
Tous les auteurs :
Mazel B, Delanne J, Garde A, Racine C, Bruel AL, Duffourd Y, Lopergolo D, Santorelli FM, Marchi V, Pinto AM, Mencarelli MA, Canitano R, Valentino F, Papa FT, Fallerini C, Mari F, Renieri A, Munnich A, Niclass T, Le Guyader G, Thauvin-Robinet C, Philippe C, Faivre L
Lien Pubmed
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.
Mots clés
FOXG1 gene, FOXG1 phenotype spectrum, congenital Rett syndrome, mild phenotype
Référence
Am J Med Genet B Neuropsychiatr Genet. 2024 03 8;:e32970