RESUMO
Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by the triad of short stature, microtia and absent or small patellae. We report on a patient with MGS secondary to biallelic mutations in CDC45 detected on whole exome sequencing (WES). Patients with MGS caused by mutations in CDC45 display a distinct phenotype characterized by craniosynostosis and anorectal malformation. Our patient had craniosynostosis, anorectal malformation and short stature, but did not have the microtia or patella hypoplasia. Our report also highlights the value of WES in aiding diagnosis of patients with rare genetic diseases. In conclusion, our case report and review of the literature illustrates the unique features of CDC45-related MGS as well as the benefits of WES in reducing the diagnostic odyssey for patients with rare genetic disorders.
Assuntos
Proteínas de Ciclo Celular/genética , Microtia Congênita/diagnóstico , Microtia Congênita/genética , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/genética , Micrognatismo/diagnóstico , Micrognatismo/genética , Patela/anormalidades , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/fisiopatologia , Malformações Anorretais/genética , Malformações Anorretais/fisiopatologia , Craniossinostoses/genética , Craniossinostoses/fisiopatologia , Feminino , Transtornos do Crescimento/congênito , Humanos , Mutação , Fenótipo , Doenças Raras/genética , Doenças Raras/fisiopatologia , Sequenciamento do ExomaRESUMO
Osteogenesis imperfecta, is a genetically and clinically heterogeneous connective tissue disorder that disrupts bone architecture, making it fragile and more prone to fractures. While more than 85% of cases are due to variants in COL1A1 and COL1A2, variants in noncollagen genes have been identified in the remaining cases. The recurring heterozygous variant in IFITM5 (c.-14C>T) leads to osteogenesis imperfecta type V, a second missense variant in IFITM5 (c.119C>T, p.Ser40Leu) leads to phenotype resembling osteogenesis imperfecta type VI. In this report, we describe the first patient with Ser40Trp variant in IFITM5, who presented with multiple fractures in the prenatal period. She remained fracture free after birth (except for trauma-related fractures during puberty) with normal bone mineral densitometry. Her mother, who did not have a history of fracture, was noted to have somatogonadal mosaicism for this variant and became pregnant with a second child with multiple prenatal fractures, found to have the same variant. To our knowledge, this is the first case of somatogonadal mosaicism in IFITM5. In addition, we have summarized the literature on patients presenting with variant in codon 40 (serine) of IFTIM5 protein.