Abstract
BACKGROUND: Wiedemann-Steiner syndrome (WSS) is a genetic malformation syndrome caused by abnormalities in KMT2A. It is characterized by developmental delays, facial dysmorphism, hypertrichosis, failure to thrive, and musculoskeletal anomalies. Expanded applications of exome sequencing have increased the number of confirmed cases, broadening our understanding of the WSS spectrum. METHODS: We collected and organized the clinical and molecular features of 10 unrelated Korean patients diagnosed with WSS using molecular analysis. Clinical characteristics were presented based on the electronic medical records of the patients' regular visits. RESULTS: Subject patients consisted of four male and six female patients. The median patient age at diagnosis was 6.76 years. In most cases, the chief complaint upon visiting a clinician was developmental delay (8/10). The most frequently observed phenotypes included failure to thrive (9/10), short stature (7/10), developmental delay (10/10), and hypertrichosis (10/10). The degree of developmental delay varied among the patients. The majority (9/10) were diagnosed by exome sequencing, with the exception of one patient (1/10) who had a microdeletion at 11q23.3, encompassing partial KMT2A, as diagnosed by chromosomal microarray. All patients had private pathogenic or Likely pathogenic variants without any recurrent variants, and nine of the 10 variants were novel. CONCLUSIONS: Most Korean patients with WSS exhibited suggestive features, but most were not pathognomonic of WSS; thus, many patients may only be identifiable by molecular analyses. Phenotypes frequently overlap with other chromatinopathy syndromes. Future studies are needed to determine the genetic background of patients with molecularly unresolved WSS and to further delineate WSS.