Phenotype in 18 Danish subjects with genetically verified CHARGE syndrome

• Published in: Clinical genetics Vol. 83; no. 2; pp. 125 - 134
• Main Authors: Husu, E, Hove, HD, Farholt, S, Bille, M, Tranebjærg, L, Vogel, I, Kreiborg, S
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2013; Wiley-Blackwell
• Subjects: Adolescent; Biological and medical sciences; Bone Diseases, Developmental - genetics; Bone Diseases, Developmental - pathology; CHARGE syndrome; CHARGE Syndrome - genetics; CHARGE Syndrome - pathology; CHD7; Child; Child, Preschool; Choanal atresia; chromo domain helicase DNA-binding protein7; Chromosome aberrations; Coloboma - genetics; Coloboma - pathology; Computed tomography; Cranial nerves; Denmark - epidemiology; Developmental Disabilities - genetics; Developmental Disabilities - pathology; DNA helicase; DNA Helicases - genetics; DNA-binding protein; DNA-Binding Proteins - genetics; Ear; Ear, External - abnormalities; Ear, External - pathology; Eye; Facial Asymmetry - genetics; Facial Asymmetry - pathology; Female; Fundamental and applied biological sciences. Psychology; Gene deletion; Genetic Association Studies; Genetic screening; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genotype; Genotype & phenotype; Hearing loss; Hearing Loss, Sensorineural - genetics; Hearing Loss, Sensorineural - pathology; Heart; Heart Defects, Congenital - genetics; Heart Defects, Congenital - pathology; Humans; Hypoplasia; Infant; Magnetic resonance imaging; Male; Medical genetics; Medical sciences; Molecular and cellular biology; Mouth Abnormalities - genetics; Mouth Abnormalities - pathology; Mutation; phenotype; Reconstruction; Retrospective Studies; swallowing; Temporal bone; Urogenital Abnormalities - genetics; Urogenital Abnormalities - pathology; Vestibular system; Denmark; Europe; Netherlands; Chromosomal aberration; Human; Nervous system diseases; Trisomy; Urinary system disease; Typing; chromo domain helicase DNA-binding protein7; CHD7; Aneuploidy; Cardiovascular disease; Genotype; Chromosome E18; Phenotype; DNA; CHARGE syndrome; ENT disease; Danish; Genetics; Complex syndrome
• ISSN: 0009-9163; 1399-0004; 1399-0004
• DOI: 10.1111/j.1399-0004.2012.01884.x

Husu E, Hove HD, Farholt S, Bille M, Tranebjærg L, Vogel I, Kreiborg S. Phenotype in 18 Danish subjects with genetically verified CHARGE syndrome. CHARGE (coloboma of the eye, heart defects, choanal atresia, retarded growth and development, genital hypoplasia and ear anomalies and/or hearing loss) syndrome is a rare genetic, multiple‐malformation syndrome. About 80% of patients with a clinical diagnose, have a mutation or a deletion in the gene encoding chromodomain helicase DNA‐binding protein 7 (CHD7). Genotype–phenotype correlation is only partly known. In this nationwide study, phenotypic characteristics of 18 Danish CHD7 mutation positive CHARGE individuals (N = 18) are presented. We studied patient records, clinical photographs, computed tomography, and magnetic resonance imaging (MRI). Information was not available for all traits in all subjects. Therefore, the results are presented as fractions. The following prevalence of cardinal symptoms were found: coloboma, 16/17; heart defects, 14/18; choanal atresia, 7/17; retarded growth and development, 11/13; genital abnormalities, 5/18; ear anomalies, 15/17 and sensorineural hearing loss, 14/15. Vestibular dysfunction (10/13) and swallowing problems (12/15) were other frequent cranial nerve dysfunctions. Three‐dimensional reconstructions of MRI scans showed temporal bone abnormalities in >85%. CHARGE syndrome present a broad phenotypic spectrum, although some clinical features are more frequently occurring than others. Here, we suggest that genetic testing for CHD7 mutation should be considered in neonates with a specific combination of several clinical symptoms.