Investigation of genetic and phenotypic heterogeneity in 37 Turkish patients with Kabuki and Kabuki-like phenotype

Kabuki syndrome (KS) is a rare disorder characterized by distinct face, persistent fingertip pads, and intellectual disability (ID) caused by mutation in KMT2D (56%-76%) or KDM6A (5%-8%). Thirty-seven children aged 1-16 years who followed for median of 6.8 years were included in this study, which aimed to investigate the genetic and clinical characteristics of KS patients. KMT2D and KDM6A were evaluated by sequencing and multiplex-ligation-dependent probe amplification in 32 patients. Twenty-one pathogenic variants in KMT2D, of which 17 were truncated and nine were novel, one frame-shift novel variant in KDM6A were identified. The molecular diagnosis rate was 68.7% (22/32). In the whole-exome sequencing analysis performed in the remaining patients, no pathogenic variant that could cause any disease was detected. All patients had ID; 43.2% were severe and moderate. We observed that facial features that became more prominent with age were enough for a possible diagnosis of KS in infancy. The frequencies of facial features, cardiac and renal anomalies, short stature, microcephaly, and epilepsy did not differ depending on whether they had truncating or nontruncating variants or were in variant-negative KS-like group. This study has expanded clinical features of the disease, as well as identified new variants in genes causing KS.