RESUMO
Stüve-Wiedemann syndrome (SWS) is a severe congenital skeletal dysplasia associated with life threatening dysautonomic manifestations. Newborns affected with this condition exhibit distinctive shortening and bowing of the long bones with reduced bone volume. The majority of affected newborns die early due to neuromuscular complications namely hyperthermia, apnea, and swallowing difficulties. In this review, we provide an overall picture on the clinical, including long-term management, molecular and cellular aspects of SWS and discuss briefly other related bent bone dysplasias.
Assuntos
Doenças do Desenvolvimento Ósseo/genética , Exostose Múltipla Hereditária/genética , Fatores de Transcrição NFI/genética , Osteocondrodisplasias/genética , Receptores de OSM-LIF/genética , Doenças do Desenvolvimento Ósseo/metabolismo , Doenças do Desenvolvimento Ósseo/patologia , Pré-Escolar , Transtornos de Deglutição/genética , Transtornos de Deglutição/metabolismo , Transtornos de Deglutição/patologia , Exostose Múltipla Hereditária/metabolismo , Exostose Múltipla Hereditária/patologia , Humanos , Lactente , Recém-Nascido , Mutação , Osteocondrodisplasias/metabolismo , Osteocondrodisplasias/patologia , Disautonomias Primárias/genética , Disautonomias Primárias/metabolismo , Disautonomias Primárias/patologiaRESUMO
Fibrochondrogenesis is documented to be a neonatally lethal rare recessively inherited disorder characterized by short-limbed skeletal dysplasia. Here we report two patients from two unrelated consanguineous Emirati families who have unexpectedly survived till the ages of 3 and 6 years. These patients show additional symptoms which include developmental delay, profound sensory-neural deafness, severe myopia and progressive severe skeletal abnormalities. Linkage of fibrochondrogenesis in the Emirati families to chromosome 1 has been established using homozygosity mapping confirming recent findings by Tompson et al. in 2010. Screening of the COL11A1 gene revealed two null homozygous mutations [c.4084C>T (p.R1362X) and c.3708+437T>G] in the aforementioned two families. The c.4084C>T mutation is predicted to introduce a stop codon at position Arg1362, whereas the c.3708+437T>G mutation causes the activation of an intronic pseudoexon between exons 48 and 49. This resulted in the insertion of 50 nucleotides into the mRNA. The carriers of these mutations display ocular defects with normal hearing. In conclusion, our data shall improve the overall understanding of fibrochondrogenesis especially in surviving homozygous patients and, at least partly, explain the phenotypic variability associated with COL11A1 gene mutations.