Novel ANKRD11 Variant in a Lebanese Girl with KBG Syndrome: An 11-Year Follow-Up
TL;DR
This case expands the molecular spectrum of KBG syndrome and highlights the importance of genomic testing in children presenting with developmental delay, learning difficulties, and subtle dysmorphic features, particularly when the diagnosis remains uncertain during early childhood.
Abstract
KBG syndrome is a rare autosomal dominant neurodevelopmental disorder caused by pathogenic variants in the ANKRD11 gene. The clinical presentation is highly variable and may include characteristic craniofacial features, developmental delay, learning disabilities, behavioral abnormalities, and growth impairment. Here we describe a Lebanese female patient who was followed for 11 years because of failure to thrive, developmental delay, attention deficit, behavioral difficulties, and persistent learning disabilities. Longitudinal follow-up documented gradual neurocognitive improvement with multidisciplinary interventions and pharmacological treatment for attention and behavioral difficulties. Whole Exome Sequencing (WES), performed at the age of 11 years, identified a novel heterozygous frameshift pathogenic variant in the ANKRD11 gene (p.Tyr808fs), confirming the diagnosis of KBG syndrome. To our knowledge, this is the first reported Lebanese patient carrying this specific ANKRD11 variant. This case expands the molecular spectrum of KBG syndrome and highlights the importance of genomic testing in children presenting with developmental delay, learning difficulties, and subtle dysmorphic features, particularly when the diagnosis remains uncertain during early childhood.