Background: Mutations in the gene encoding the Chromodomain Helicase DNA-binding protein 7 (CHD7) are found in 60% of patients with CHARGE Syndrome (Coloboma, Heart Defects, Choanal Atresia, Retarded growth and development, Genital hypoplasia, Ear abnormalities and/or hearing problems) and in 6% of patients with Kallmann syndrome.
Objectives and hypotheses: To describe a novel CHD7 mutation and its clinical presentation.
Methods: Case report with clinical evaluation, endocrine investigations, neuroimaging and genetic analysis were performed.
Results: 13.5 year-old male was addressed for investigation of pubertal and growth delay. Family history was marked by delayed puberty in both parents. The patient was born full term; eutrophic after an uneventful pregnancy. He was operated at 5 days of life for bilateral choanal atresia. Development was normal. Height and weight were −2.04 SDS and −1.74 SDS respectively. He exhibited a Tanner A1P2G1 stage with micropenis (4×1 cm). Gonadotrophines were low (LH:0.2U/L, FSH:0.9U/L); At age 14, LHRH test suggested hypogonadotrophic hypogonadism. Sniffing test revealed complete anosmia. MRI demonstrated semi-circular canal and olfactory bulb hypoplasia, vestibular, cochlear and right VII cranial nerve malformation, and a decreased hypophyseal volume (160 mm3). According to the Verloes 2005 Criteria, the patient was diagnosed with partial CHARGE syndrome. We identified a de novo heterozygous CHD7 mutation (c.4234T>G, pTyr1412Asp) located in the Helicase C domain. This is a private variant, absent in ExAC database and predicted to be deleterious by 10/10 prediction algorithms.
Discussion and conclusion: CHARGE syndrome remained undiagnosed in this patient until adolescence despite the presence of suggestive features. Genetic testing promotes the broadening of phenotypic and genotypic spectrum of CHARGE syndrome and may give insight to the mild end of phenotypic spectrum, ensuring optimal follow up and appropriate genetic counselling.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology