RESUMO
Xia-Gibbs syndrome (XGS) is a neurodevelopmental disorder characterized by intellectual disability, developmental delay, seizures, hypotonia, obstructive sleep apnoea and mild facial dysmorphism. Heterozygosity for loss-of-function variants in AHDC1, encoding the AT-hook DNA binding motif containing protein 1, were discovered in 2014 as the likely genetic cause of Xia-Gibbs syndrome. We present five patients with Xia-Gibbs syndrome caused by previously unreported variants in AHDC1. Two of the patients share a frameshift variant: c.2849del (p.(Pro950Argfs*192)) in AHDC1. Despite sharing this variant, the two patients show remarkable phenotypic differences underscoring the clinical heterogeneity of Xia-Gibbs syndrome. In addition, we present a case of Xia-Gibbs syndrome caused by mosaicism for an AHDC1 variant.
Assuntos
Anormalidades Craniofaciais/genética , Proteínas de Ligação a DNA/genética , Deficiências do Desenvolvimento/genética , Deformidades do Pé/genética , Hipotonia Muscular/genética , Fenótipo , Adolescente , Adulto , Anormalidades Craniofaciais/patologia , Deficiências do Desenvolvimento/patologia , Feminino , Deformidades do Pé/patologia , Mutação da Fase de Leitura , Humanos , Masculino , Hipotonia Muscular/patologia , Síndrome , Adulto JovemRESUMO
The molecular background for osteogenesis imperfecta (OI) is mutations in one of the two genes (COL1A1 and COL1A2) encoding collagen I. The disease is characterised by varying degrees of fragile bones, retarded growth, bone deformities, tooth abnormalities, blue sclerae, and hearing loss. Treatment with bisphosphonates reduces the incidence of fractures in children with severe OI, while this still remains to be demonstrated in adults. Results from bone marrow transplantation and animal experiments may lead to alternative treatment in severe OI.
