2.4 Clinical delineation and genotype–phenotype correlation in 104 children with Kabuki syndrome: a single-center, cross-sectional and follow-up study in China

Yirou Wang; Feihan Hu; eqiong Xu; Jun Tan; Tingting Yu; Niu Li; Qian Li; Yao Chen; Guoying Chang; Xiuqi Ma; Ding Yu; Xiumin Wang

doi:10.1530/ey.22.2.4

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ESPE Yearbook of Paediatric Endocrinology (2025) 22 2.4 | DOI: 10.1530/ey.22.2.4

ESPEYB25 2. Antenatal and Neonatal Endocrinology Rare Syndromes (3 abstracts)

2.4 Clinical delineation and genotype-phenotype correlation in 104 children with Kabuki syndrome: a single-center, cross-sectional and follow-up study in China

Yirou Wang , Feihan Hu , Xueqiong Xu , Jun Tan , Tingting Yu , Niu Li , Qian Li , Yao Chen , Guoying Chang , Xiuqi Ma , Ding Yu & Xiumin Wang

Eur J Pediatr 2025 Mar 27;184(4):271.doi: 10.1007/s00431-025-06103-x

Brief Summary: This is an important longitudinal study of 104 Chinese patients with Kabuki syndrome (KS, OMIM #147920 and #300867), and the largest to date. It provides the first growth curves for this rare syndrome based on WHO 2007 standards, as well as detailed phenotypic data.

In order to be included, all patients had pathogenic or likely pathogenic variants in KMT2D or KDM6A (both encode histone demethylases) on whole genome sequencing followed by Sanger sequencing. Facial recognition software (Face2Gene) correctly identified 85 patients of the 99 patients providing photographs, with some concern for photograph quality for those not confirmed.

In the 89 patients with KMT2D mutations (KS1), 78 variants were scattered throughout the gene but 29.2% were within exon 39. In the 15 KS2 patients with KDM6A mutations, 14 different variants were reported. Predicted adult height data (excluding GH deficient/treated patients): KS1-Male -1.43 SD, KS1-Female -1.86 SD,KS2-Male -1.26 SD, KS2-Female -0.98 SD. Growth kinetics suggested that, in addition to a 25-30% incidence of fetal growth restriction and stature < -2 SD in ~30% of patients, they lack a pubertal growth spurt. While all patients with KS1 had intellectual disabilities, some with KS2 mutations had intelligence in the normal range; a very high proportion (60-80%) had dysarthria, and renal, cardiac and cleft palate are among the notable malformations.

This paper should improve our diagnostic suspicion for KS and prompt consideration of facial dysmorphology software to make a diagnosis, pending genetic testing.