A Case of CHARGE Syndrome with a Novel Intronic Variant in the CHD7 Gene

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What is already known on this topic?CHARGE syndrome is an autosomal dominant disorder.The characteristic findings of the syndrome include coloboma (C), heart anomalies (H), choanal atresia (A), growth and developmental delay (R), genitourinary system anomalies (G), and ear anomalies and/or hearing loss (E).The CHD7 gene is currently the only confirmed pathogenic gene associated with CHARGE syndrome and is known to be widely expressed in both embryonic and adult tissues.Although numerous pathogenic variants have been identified, intronic variations in CHD7 remain exceedingly rare. What this study adds?This study reports a novel heterozygous intronic variant (c.5050+2T>C) in intron 22 of the CHD7 gene in a patient with classical features of CHARGE syndrome.The identification of this rare variant highlights the clinical relevance of intronic mutations and contributes to the growing body of genetic data associated with the syndrome.ABSTRACT CHARGE syndrome is an autosomal dominant disorder caused by variations in the CHD7 gene.The characteristic findings of the syndrome include coloboma (C), heart anomalies (H), choanal atresia (A), growth and developmental delay (R), genitourinary system anomalies (G), and ear anomalies and/or hearing loss (E).A 7.7-years-old male patient was initially referred after a partial empty sella appearance was noted on brain imaging during evaluation for developmental delay at 10 months of age.He had undergone surgery for choanal atresia and congenital heart disease.The patient exhibited severe postnatal growth retardation, hypertelorism, ep canthal folds, cleft palate, a thin upper lip, bilateral ear anomalies, preaxial polydactyly, and bilateral undescended testes.He had motor and mental developmental delay.Ophthalmologic examination showed retinal atrophy and coloboma.Genetic analysis identified a novel heterozygous c.5050+2T>C variant in intron 22 of the CHD7 gene, confirming the diagnosis of CHARGE syndrome.Furthermore, the patient had undergone bilateral orchiopexy at two years of age, and growth hormone therapy was initiated after a diagnosis of complete growth hormone deficiency at 19 months of age.A novel heterozygous variant in the CHD7 gene was identified in a patient, who presented with classical signs of CHARGE sydrome.Early recognition and diagnosis is important to enable initiation of timely treatment of potential complications associated with the disorder.