Recognizing KBG syndrome in pediatric practice: a case series highlighting phenotypic variability and diagnostic clues
TL;DR
This Saudi case series adds to the growing evidence of clinical heterogeneity in KBGS, suggesting possible underrecognized systemic involvement and cautious interpretation is required given the small sample size.
Abstract
Background KBG syndrome (KBGS) is a rare autosomal dominant neurodevelopmental disorder caused by heterozygous pathogenic variants in ANKRD11. It is characterized by developmental delay, intellectual disability, behavioral difficulties, macrodontia, craniofacial dysmorphism, short stature, and skeletal anomalies. Objectives To describe the clinical, radiological, and molecular findings of Saudi patients with molecularly confirmed KBGS and compare their presentation with reported features in the literature. Methods We conducted a retrospective case series at King Faisal Specialist Hospital and Research Centre, Riyadh, between January 2002 and December 2024. Clinical, dysmorphological, developmental, behavioral, family history, neuroimaging, and molecular data were reviewed for three pediatric patients with confirmed ANKRD11-related KBGS. Results All patients demonstrated core features of KBGS, including intellectual disability, speech and motor delay, learning difficulties, and behavioral manifestations such as autism spectrum features or aggression. Common dysmorphic findings included long philtrum and prominent ears in all patients, with a triangular face, macrodontia, and synophrys observed in two patients. Short stature and skeletal anomalies were also present. Molecular testing identified heterozygous pathogenic or likely pathogenic ANKRD11 variants: NM_013275.6:c.4087C > T (p.Arg1363Ter), NM_013275.6:c.3382_3383del (p.Asp1128GlufsTer41), and NM_013275.6:c.1977C > G (p.Tyr659Ter). All variants were predicted to result in premature termination. Renal fusion and complex vertebral anomalies were observed, suggesting possible underrecognized systemic involvement, although cautious interpretation is required given the small sample size. Conclusion This Saudi case series adds to the growing evidence of clinical heterogeneity in KBGS. Early recognition, molecular confirmation, multidisciplinary care, and longitudinal follow-up are essential to improve diagnosis, surveillance, and management.