Clinical and genetic characteristics of and diagnostic insights on KBG syndrome in Chinese patients: a retrospective study and literature review

Most published cohorts of individuals with KBG are Caucasian which limits the understanding of the genetic diversity and clinical presentation across ethnicities. Herein, we report Chinese patients with KBGS, summarise their clinical and genetic characteristics, and compare their characteristics with those of non-Chinese patients. We retrospectively analysed the data of 65 Chinese patients, identified 33 previously unreported cases, and compared their data with those of 519 non-Chinese patients. We noted the most prevalent features in Chinese patients. Large and/or prominent ears, triangular faces, anteverted nares, synophrys, long philtrum, low hairline, spinal anomalies, and recurrent otitis media differed significantly among ethnicities. Among the 51 patients with the c.1903_1907del variant, there were differences across ethnicities; the c.1903_1907del and non-c.1903_1907del variants differed among Chinese patients. Rare phenotypes were identified in Chinese patients. The incidence of IUGR, polyhydramnios, abnormal renal and brain morphology, abnormal cardiovascular system morphology, preterm birth, and higher NT was higher in all patients. Genetic sequencing revealed 14 unreported variants. Eight patients were treated with recombinant human growth hormone and had increased height without significant adverse effects. Our findings support the consideration of KBGS in the differential diagnosis when specific prenatal features (such as IUGR and polyhydramnios) are present. In such scenarios, referral for genetic counseling to discuss the option of testing for ANKRD11 variants and 16q24.3 microdeletions is a prudent clinical step.Overall, Chinese patients with KBGS appear to tolerate growth hormone treatment, but further studies are needed to confirm its long-term safety and efficacy.