Kabuki syndrome (KS) is a rare disorder of transcriptional regulation with a complex phenotype that includes cranio-facial dysmorphism, intellectual disability, hypotonia, failure to thrive, short stature, and cardiac and renal anomalies. Heterozygous, de novo dominant mutations in either KMT2D or KDM6A underlie KS. Limited information is available about the phenotypic spectrum of KS in China. Fourteen Chinese patients with genetically confirmed KS were evaluated in addition to 11 Chinese patients who were identified from the medical literature. The clinical phenotype spectrum of these patients was compared to that of 449 patients with KS from non-Chinese ethnicities. Additionally, we explored the utility of a facial recognition software in recognizing KS. All 25 patients with KS carried de novo, likely pathogenic or pathogenic variants in either KMT2D or KDM6A. Eighteen patients were male, the age at diagnosis ranged from 2months to 11.6âyears. The facial gestalt included arched and broad eyebrows (25/25; 100%), sparse lateral or notched eyebrows (18/18; 100%), short columella with a concave nasal tip (24/25; 96%) and large, prominent ears (24/24; 100%) which were more frequent in Chinese patients (pâ<â.01). In contrast, microcephaly (2/25; 8%), cleft lip/palate (2/25; 8%), and cardiac defects (10/25; 40%) were less frequent in Chinese patients (not significant). The diagnosis of KS was correctly identified in 13 of 14 patients through facial recognition and clinical phenotyping, underscoring the utility of this approach. As expected, there is marked phenotypic overlap between Chinese and non-Chinese patients with KS, although subtle differences were identified.
KEYWORDS: KDM6A, KMT2D, Chinese, Kabuki syndrome