TY - JOUR
T1 - Individual clinically diagnosed with CHARGE syndrome but with a mutation in KMT2D, a gene associated with Kabuki syndrome
T2 - A case report
AU - Sakata, Sonoko
AU - Okada, Satoshi
AU - Aoyama, Kohei
AU - Hara, Keiichi
AU - Tani, Chihiro
AU - Kagawa, Reiko
AU - Utsunomiya-Nakamura, Akari
AU - Miyagawa, Shinichiro
AU - Ogata, Tsutomu
AU - Mizuno, Haruo
AU - Kobayashi, Masao
N1 - Funding Information:
The authors would like to thank Ohnishi Hidenori (Department of Pediatrics, Graduate School of Medicine, Gifu University) for helpful discussion. They thank Sarah Williams, Ph.D., from Edanz Group (https://www.edanzediting.com) for editing a draft of this manuscript. This study was supported in part by the Practical Research Project for Rare/Intractable Diseases from the Japan Agency for Medical Research and Development, AMED
PY - 2017/12/11
Y1 - 2017/12/11
N2 - 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.
AB - 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.
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U2 - 10.3389/fgene.2017.00210
DO - 10.3389/fgene.2017.00210
M3 - Article
AN - SCOPUS:85038005540
VL - 8
JO - Frontiers in Genetics
JF - Frontiers in Genetics
SN - 1664-8021
IS - DEC
M1 - 210
ER -