IllnessKBG syndrome, differential diagnosis I

NGS +

KBG syndrome affects multiple body systems. Abnormal facial features include macrodontia, brachycephaly, triangular face, hypertelorism, synophris, long philtrum and thin upper lip. Skeletal anomalies concern delayed bone age and often brachydactyly. The slow physical and mental development is accompanied by hyperactivity or autism spectrum disorder including mental retardation. Less common are hearing loss, seizures and heart defects. KBG syndrome is inherited in an autosomal dominant manner, but 2/3 of the mutations occur de novo, with deletions and insertions diagnosed as causative in nearly 30% of cases. The proportion of patients with clinical KBG findings without detectable ANKRD11 gene mutation is unknown. Therefore, a negative molecular genetic result does not represent exclusion of the clinical diagnosis. For differential diagnostic purposes additional syndromes (transmitted partially via different inheritance patterns) can be considered: Aarskog syndrome, Cohen syndrome and Cornelia de Lange syndrome.

• Alias: Kleinwuchs, faziale + skelettale Anomalien, Intelligenzminderung, Makrodontie
• Allelic: Mungan syndrome (RAD21)
• KBG syndrome (ANKRD11)
• Aarskog-Scott syndrome (FGD1)
• Cohen syndrome (VPS13B)
• Cornelia de Lange syndrome 1 (NIPBL)
• Cornelia de Lange syndrome 2 (SMC1A)
• Cornelia de Lange syndrome 3 ((SMC3)
• Cornelia de Lange syndrome 4 (RAD21)
• Cornelia de Lange syndrome 5 (HDAC8)
• Developmental + epileptic encephalopathy 85, with/-out midline brain defects (SMC1A)
• Mental retardation, XL syndromic 16 (FGD1)