Clinical delineation and genotype-phenotype correlation in 104 children with kabuki syndrome: A single-center, cross-sectional and follow-up study in China.

Abstract

This study provides a detailed genotype and phenotype analysis of a large longitudinal cohort of Kabuki Syndrome (KS) from a single center in China. From July 2017 to July 2024, participants were enrolled at Shanghai Children's Medical Center. Variants in KMT2D or KDM6A were identified through whole exome sequencing. Phenotype data included prenatal and perinatal history, neonatal, childhood and adolescence evaluations. A total of 104 KS individuals fullfiled 362 outpatient visits, with an average follow-up of 2.58 years and a median follow-up time of 1.75 years. Growth curves were plotted based on 433 height data points. Among the patients, 27.08% had congenital heart defects (CHD), and 3 patients were identified with anomalous pulmonary venous connection as a new KS phenotype. KS patients showed facial feature heterogeneity, patients with atypical facial features associated with a older diagnosis age and a more diverse and severe phenotype. Among the 99 KS patients who provided facial photographs, the Face2Gene software was able to make accurate diagnoses in 85 individuals. The remaining 14 individuals may have had incorrect diagnoses because the provided photographs were not frontal facial images.

Conclusion: This study offered a comprehensive description of a Chinese KS cohort, and provided the first growth curves and a detailed CHD phenotype spectrum of Chinese KS patients. Our findings also suggest that, despite requirements for photograph quality, facial recognition software will be of significant value in the clinical diagnosis of KS.

What is known: • Kabuki syndrome is a rare disease that affects multiple systems. • Short stature is one of the common clinical manifestations of Kabuki syndrome.

What is new: • The genotypes and phenotypes of patients with Kabuki syndrome in China have been described in detail. • Growth curves for patients with Kabuki syndrome in China have been established.