Expanding the Evaluation of Skeletal Anomalies in Patients With KBG Syndrome: Recommendations for Clinical Practice

KBG syndrome is a rare autosomal dominant neurodevelopmental disorder caused by ANKRD11 haploinsufficiency and is characterized by short stature, distinctive facial features, intellectual disability or developmental delay, congenital anomalies and skeletal anomalies. Although skeletal anomalies are reported in about 75% of cases, their nature and extent in relation to growth are largely unknown. Therefore, this study aims to asses the prevalence of skeletal anomalies in KBG syndrome and explore whether there is a relationship with short stature. This retrospective cohort study includes patients with a confirmed diagnosis of KBG syndrome, with available radiographic images at the Radboud University Medical Center. The radiographs were re-evaluated by a radiologist focusing on the presence of spinal, costal, vertebral, and hand anomalies using standardized radiological criteria. In our cohort of 38 persons with KBG syndrome, 92% show skeletal anomalies on radiographic imaging. The most frequent observations on the radiographs were spinal anomalies (74%) and costal anomalies (40%). Specifically, lordosis (36%) had the highest prevalence. Patients with short stature (n = 14) showed higher prevalences of kyphosis and delayed skeletal age. In conclusion, this study demonstrates a high prevalence and broad variety of skeletal anomalies in individuals with KBG syndrome.