Abstract
Introduction: Skeletal dysplasias constitute an important differential diagnosis in chromosomally inconspicuous fetuses with growth retardation. Skeletal dysplasias include a number of disorders, with varying consequences for fetal survival and a differing risk for repeat occurrence. In the case presented here, we show how, despite the absence of an index patient, a combination of first-trimester ...
Abstract
Introduction: Skeletal dysplasias constitute an important differential diagnosis in chromosomally inconspicuous fetuses with growth retardation. Skeletal dysplasias include a number of disorders, with varying consequences for fetal survival and a differing risk for repeat occurrence. In the case presented here, we show how, despite the absence of an index patient, a combination of first-trimester ultrasound and targeted DNA diagnostics offer the possibility of an exact diagnosis which is essential for the counseling of affected families. Methods: A healthy nullipara presented in the 12 + 4 GW with pronounced enlarged nuchal transparency (nuchal fold > 10 mm). The subsequent fetal sonography showed shortened ribs, a negative A-wave in the flow of the ductus venosus and tetramicromelia, which suggested a lethal form of skeletal dysplasia. The differential diagnosis thus included thanatophoric dysplasia and the three subtypes of achondrogenesis (ACG). Based on this, the possible gene localization could be narrowed down to three genes. Results: A homozygous frame shift mutation in the sulfate transporter gene SLC26A2 was identified in DNA from the chorion biopsy. This resulted in a diagnosis of autosomal recessive achondrogenesis type IB (ACG1B; OMIM 600972). The certainty of a lethal prognosis and a risk of repeat occurrence of 25% for ACG1B permitted the family to come to an informed decision regarding the current pregnancy and their further family planning. Conclusion: The combination of ultrasound and genetics permits the exact diagnosis of certain lethal skeletal dysplasias already in the first trimester, even without an index patient. This is of far reaching importance both for current and future pregnancies.
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