Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Medical Genetics Center, Asan Medical Center, Seoul, Republic of Korea.
J Hum Genet. 2024 Sep;69(9):417-423. doi: 10.1038/s10038-024-01258-1. Epub 2024 Jun 1.
Kabuki syndrome (KS) is a rare disorder characterized by typical facial features, skeletal anomalies, fetal fingertip pad persistence, postnatal growth retardation, and intellectual disabilities. Heterozygous variants of the KMT2D and KDM6A genes are major genetic causes of KS. This study aimed to report the clinical and genetic characteristics of KS.
This study included 28 Korean patients (14 boys and 14 girls) with KS through molecular genetic testing, including direct Sanger sequencing, whole-exome sequencing, or whole-genome sequencing.
The median age at clinical diagnosis was 18.5 months (IQR 7-58 months), and the median follow-up duration was 80.5 months (IQR 48-112 months). Molecular genetic testing identified different pathogenic variants of the KMT2D (n = 23) and KDM6A (n = 3) genes, including 15 novel variants. Patients showed typical facial features (100%), such as long palpebral fissure and eversion of the lower eyelid; intellectual disability/developmental delay (96%); short stature (79%); and congenital cardiac anomalies (75%). Although 71% experienced failure to thrive in infancy, 54% of patients showed a tendency toward overweight/obesity in early childhood. Patients with KDM6A variants demonstrated severe genotype-phenotype correlation.
This study enhances the understanding of the clinical and genetic characteristics of KS.
歌舞伎综合征（KS）是一种罕见的疾病，其特征为典型的面部特征、骨骼异常、胎儿指尖垫持续存在、出生后生长迟缓以及智力障碍。KMT2D 和 KDM6A 基因的杂合变异是 KS 的主要遗传原因。本研究旨在报告 KS 的临床和遗传特征。
本研究通过分子遗传学检测，包括直接 Sanger 测序、外显子组测序或全基因组测序，纳入了 28 名韩国 KS 患者（14 名男孩和 14 名女孩）。
临床诊断时的中位年龄为 18.5 个月（IQR 7-58 个月），中位随访时间为 80.5 个月（IQR 48-112 个月）。分子遗传学检测发现了 KMT2D（n=23）和 KDM6A（n=3）基因的不同致病性变异，包括 15 个新变异。患者表现出典型的面部特征（100%），如长睑裂和下眼睑外翻；智力障碍/发育迟缓（96%）；身材矮小（79%）；和先天性心脏异常（75%）。尽管 71%的患者在婴儿期存在生长不良，但 54%的患者在幼儿期有超重/肥胖的趋势。KDM6A 变异患者表现出严重的基因型-表型相关性。
本研究加深了对 KS 的临床和遗传特征的认识。
