Diastrophic dysplasia: prenatal diagnosis and review of the literature

Abstract

CONTEXT: Diastrophic dysplasia is a type of osteochondrodysplasia caused by homozygous mutation in the gene DTDST (diastrophic dysplasia sulfate transporter gene). Abnormalities occurring particularly in the skeletal and cartilaginous system are typical of the disease, which has an incidence of 1 in 100,000 live births. CASE REPORT: The case of a pregnant woman, without any consanguineous relationship with her husband, whose fetus was diagnosed with skeletal dysplasia based on ultrasound findings and DNA tests, is described. An obstetric ultrasound scan produced in the 16 th week of gestation revealed characteristics that guided the clinical diagnosis. Prominent among these characteristics were rhizomelia of the lower and upper limbs (shortening of the proximal portions) and mesomelia (shortening of the intermediate portions). Both upper limbs showed marked curvature, with the first finger of the upper limbs in abduction and clinodactyly of the fifth finger. Molecular analysis using the polymerase chain reaction (PCR) and gene sequencing detected mutations that had already been described in the literature for the gene DTDST, named c.862C > T and c.2147_2148insCT. Therefore, the fetus was a compound heterozygote, carrying two different mutations. CONCLUSIONS: Prenatal diagnosis of this condition allowed a more realistic interpretation of the prognosis, and of the couple's reproductive future. This case report shows the contribution of molecular genetics towards the prenatal diagnosis, for which there are few descriptions in the literature. RESUMOCONTEXTO: A displasia diastrófica é uma osteocondrodisplasia causada por mutação homozigótica no gene DTDST (diastrophic dysplasia sulfate transporter gene). As alterações, principalmente nos sistemas esquelético e cartilaginoso, são típicas dessa doença, que tem uma incidência de 1 em 100.000 nascidos vivos. RELATO DO CASO: Descreve-se o caso de uma mulher gestante, sem relação consanguínea com o seu marido, cujo feto foi diagnosticado com displasia esquelética baseado na ultrassonografia e em testes de DNA. A ultrassonografia obstétrica, realizada na 16 a semana, revelou características que guiaram o diagnóstico clínico. Entre elas, se destacam os membros inferiores e superiores com rizomelia (encurtamento das porções proximais) e mesomelia (encurtamento das porções intermediárias), ambos os membros superiores mostraram acentuada flexão, o primeiro dedo em abdução nas extremidades superiores e clinodactilia do quinto dedo. A análise molecular pela reação em cadeia da polimerase (PCR) e o sequenciamento gênico detectou mutações já descritas na literatura para o gene DTDST, chamado c.862C > T e c.2147_2148insCT. Portanto, o feto é um heterozigoto composto, carreando duas mutações diferentes. CONCLUSÕES: O diagnóstico pré-natal dessa condição permite uma interpretação mais realista do prognóstico e do futuro reprodutivo do casal. Este relato de caso mostra a contribuição da genética molecular no diagnóstico pré-natal, com poucas descrições na literatura.

Neuroimaging Findings in Pediatric Genetic Skeletal Disorders: A Review

“…General information: Rare form of short limbed dwarfism recognizable at birth; incidence is 1 in 100,000 live births …”

First trimester three-dimensional ultrasonographic diagnosis of diastrophic dysplasia: a case report and review of the literature

“…Long bone shortening and hitchhiker thumbs were shown in all these cases. Details are given in Table 1 [1,3,4,[7][8][9]11]. Additional abnormalities in this case were cleft palate, micrognathia, low-set ears, small nose, and hemangioma.…”

“…The c.862 C > T (R279W) mutation is the most common mutation in Caucasians [6]. Honório et al first revealed the prenatal molecular diagnosis of diastrophic dysplasia without previous history [3].…”

Diastrophic Dysplasia : A Case Report

“…Recently, with the advent of prenatal molecu-lar diagnosis, there has been a reduction in diagnostic errors. 7 Antenatal diagnosis can be offered for the next pregnancy through ultrasound screening of fetus for abnormal thumb and short limbs. 15 In this report neither the parents has consanguinity nor there is history of DTD in their families.…”

“…In 1990, there were 160 Finns patients with skeletal dysplasia, while there were fewer than 300 patients in rest of the world. 7,8 Clinical presentation of this disorder may confuse with other form of dwarfism with bone disorder. Frequency of occurrence of this condition is not known in our country.…”