Genotypic and Phenotypic Landscape of KBG Syndrome: A Study of 23 Turkish Individuals.

Journal: American Journal Of Medical Genetics. Part A
Published:
Abstract

KBG syndrome is a rare autosomal dominant disorder caused by ANKRD11 variants, characterized by distinctive craniofacial features, short stature, skeletal anomalies, and neurodevelopmental impairment. Regional studies, particularly from underrepresented populations, are essential to broaden the clinical and molecular spectrum of the syndrome. We retrospectively analyzed the clinical, molecular, and anthropometric data of 23 Turkish individuals with molecularly confirmed KBG syndrome. Molecular analyses included whole exome sequencing, clinical exome sequencing, and targeted gene panels. Variants were classified according to ACMG guidelines, and phenotypic features were systematically assessed using standardized criteria. Eighteen distinct ANKRD11 pathogenic or likely pathogenic variants were identified, including eight novel variants, predominantly located in exon 9. Short stature (height SDS < -2) was documented in 30.4% of patients. Intellectual disability was observed in 82.6%, and behavioral anomalies in 52.2% of the cohort. Craniofacial dysmorphism, including long philtrum, triangular facial shape, and macrodontia, was prominent. No genotype-phenotype correlation could be established. This study expands the mutational landscape of ANKRD11 and underscores the clinical variability of KBG syndrome in a Turkish cohort. Our findings emphasize the importance of integrating molecular and detailed clinical evaluations for early diagnosis, especially in diverse populations with limited prior representation.

Authors
Enise Avci Durmusalioglu, Esra Isik, Turkan Turkut Tan, Yusuf Dogan, Banu Nur, Burcu Yeter, Aslihan Sanri, Dilek Uludag Alkaya, Serife Ozturk Yilmaz, Akcahan Akalin, Gizem Urel Demir, Aysegul Yilmaz, Merve Sogukpinar, Oznur Yilmaz Bayer, Ozlem Giray Bozkaya, Ozlem Sezer, Pelin Simsek Kiper, Gulen Utine, Beyhan Tuysuz, Ozgur Cogulu, Ercan Mihci, Tahir Atik
Relevant Conditions

KBG Syndrome