Individual Clinically Diagnosed with CHARGE Syndrome but with a Mutation in KMT2D, a Gene Associated with Kabuki Syndrome: A Case Report

Frontiers in Genetics

Chihiro Tani¹  Kohei Aoyama²  Tsutomu Ogata³  Sonoko Sakata⁴  Akari Utsunomiya-Nakamura⁴  Reiko Kagawa⁴  Satoshi Okada⁴  Masao Kobayashi⁴  Haruo Mizuno⁵  Keiichi Hara⁶  Shinichiro Miyagawa⁷ 

[1] Department of Diagnostic Radiology, Hiroshima University Graduate School of Biomedical and Health Science, Hiroshima, Japan;Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan;Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan;Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan;Department of Pediatrics, International University of Health and Welfare School of Medicine, Chiba, Japan;Department of Pediatrics, National Hospital Organization Kure Medical Center, Kure, Japan;Miyagawa Kid’s Clinic, Hiroshima, Japan;

关键词: CHARGE syndrome;    Kabuki syndrome;    KMT2D;    CHD7;    phenotypic overlap;   

DOI  :  10.3389/fgene.2017.00210

来源: DOAJ

【 摘 要 】

We report a Japanese female patient presenting with classic features of CHARGE syndrome, including choanal atresia, growth and development retardation, ear malformations, genital anomalies, multiple endocrine deficiency, and unilateral facial nerve palsy. She was clinically diagnosed with typical CHARGE syndrome, but genetic analysis using the TruSight One Sequence Panel revealed a germline heterozygous mutation in KMT2D with no pathogenic CHD7 alterations associated with CHARGE syndrome. Kabuki syndrome is a rare multisystem disorder characterized by five cardinal manifestations including typical facial features, skeletal anomalies, dermatoglyphic abnormalities, mild to moderate intellectual disability, and postnatal growth deficiency. Germline mutations in KMT2D underlie the molecular pathogenesis of 52–76% of patients with Kabuki syndrome. This is an instructive case that clearly represents a phenotypic overlap between Kabuki syndrome and CHARGE syndrome. It suggests the importance of considering the possibility of a diagnosis of Kabuki syndrome even if patients present with typical symptoms and meet diagnostic criteria of CHARGE syndrome. The case also emphasizes the impact of non-biased exhaustive genetic analysis by next-generation sequencing in the genetic diagnosis of rare congenital disorders with atypical manifestations.

【 授权许可】

Unknown