KBG syndrome

KBG syndrome (also known as KBG acronym syndrome, named after the initials of the first families described) is a rare genetic disorder characterized by a distinctive combination of macrodontia (abnormally large upper central incisors), characteristic facial features, skeletal anomalies, short stature, and developmental delay or intellectual disability. The condition is caused by pathogenic variants in the ANKRD11 gene on chromosome 16q24.3, or less commonly by 16q24.3 microdeletions encompassing this gene. ANKRD11 encodes a protein involved in chromatin remodeling and transcriptional regulation, which explains the broad developmental impact of the disorder. The facial features of KBG syndrome are often recognizable and include a triangular face shape, broad or bushy eyebrows that may be synophrys (joined in the midline), a wide nasal bridge, a long philtrum, a thin upper lip, and prominent ears. Macrodontia of the permanent upper central incisors is considered a hallmark feature and is present in the majority of affected individuals. Skeletal findings commonly include brachydactyly (short fingers), costal (rib) anomalies, delayed bone age, and characteristic hand findings. Short stature is frequently observed, and many individuals have mild to moderate intellectual disability with speech and language delay. Seizures occur in approximately 25-50% of patients. Hearing loss, both conductive and sensorineural, has been reported in a subset of individuals. Behavioral features, including anxiety and attention difficulties, may also be present. There is currently no cure or disease-specific treatment for KBG syndrome. Management is supportive and multidisciplinary, tailored to the individual's specific needs. This may include speech therapy, occupational therapy, educational support, growth hormone evaluation for short stature, antiepileptic medications for seizures, audiological monitoring, and dental management for macrodontia. Early intervention programs are recommended to optimize developmental outcomes. With appropriate support, many individuals with KBG syndrome can achieve meaningful developmental progress. The condition is increasingly recognized due to wider availability of genetic testing, and the true prevalence is likely higher than currently estimated.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about KBG syndrome