Phenotype and genotype analysis of a French cohort of 119 patients with CHARGE syndrome.

Fiche publication

Date publication

décembre 2017

Journal

American journal of medical genetics. Part C, Seminars in medical genetics

Auteurs

Membres identifiés du Cancéropôle Est :
Pr FAIVRE Laurence

Tous les auteurs :
Legendre M, Abadie V, Attié-Bitach T, Philip N, Busa T, Bonneau D, Colin E, Dollfus H, Lacombe D, Toutain A, Blesson S, Julia S, Martin-Coignard D, Geneviève D, Leheup B, Odent S, Jouk PS, Mercier S, Faivre L, Vincent-Delorme C, Francannet C, Naudion S, Mathieu-Dramard M, Delrue MA, Goldenberg A, Héron D, Parent P, Touraine R, Layet V, Sanlaville D, Quélin C, Moutton S, Fradin M, Jacquette A, Sigaudy S, Pinson L, Sarda P, Guerrot AM, Rossi M, Masurel-Paulet A, El Chehadeh S, Piguel X, Rodriguez-Ballesteros M, Ragot S, Lyonnet S, Bilan F, Gilbert-Dussardier B

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/29178447

Résumé

CHARGE syndrome (CS) is a genetic disorder whose first description included Coloboma, Heart disease, Atresia of choanae, Retarded growth and development, Genital hypoplasia, and Ear anomalies and deafness, most often caused by a genetic mutation in the CHD7 gene. Two features were then added: semicircular canal anomalies and arhinencephaly/olfactory bulb agenesis, with classification of typical, partial, or atypical forms on the basis of major and minor clinical criteria. The detection rate of a pathogenic variant in the CHD7 gene varies from 67% to 90%. To try to have an overview of this heterogenous clinical condition and specify a genotype-phenotype relation, we conducted a national study of phenotype and genotype in 119 patients with CS. Selected clinical diagnostic criteria were from Verloes (2005), updated by Blake & Prasad (). Besides obtaining a detailed clinical description, when possible, patients underwent a full ophthalmologic examination, audiometry, temporal bone CT scan, gonadotropin analysis, and olfactory-bulb MRI. All patients underwent CHD7 sequencing and MLPA analysis. We found a pathogenic CHD7 variant in 83% of typical CS cases and 58% of atypical cases. Pathogenic variants in the CHD7 gene were classified by the expected impact on the protein. In all, 90% of patients had a typical form of CS and 10% an atypical form. The most frequent features were deafness/semicircular canal hypoplasia (94%), pituitary defect/hypogonadism (89%), external ear anomalies (87%), square-shaped face (81%), and arhinencephaly/anosmia (80%). Coloboma (73%), heart defects (65%), and choanal atresia (43%) were less frequent.