Lethal short-limbed platyspondylic dwarfism, torrance type

Abstract

A male fetus was delivered at 20 weeks gestation following an ultrasound diagnosis of a lethal skeletal dysplasia. This was the first baby for a non-consanguineous northern European Australian couple with no relevant family history. At post-mortem there was micromelia with bowing of the long bones, brachydactyly, a narrow, bell-shaped thorax but normal trunk length. There was mild macrocephaly, a low nasal bridge but no clover leaf skull. Internally the lungs were hypoplastic and the temporal lobes of the brain were larger than expected with a posterior link. Radiology showed small platyspondylic vertebral bodies with poor ossification, shortening of long limb bones, curved radii and irregular and flared metaphyses. Histology of bones revealed disorganisation of growth plates with some chondrocytes showing large rough endoplasmic reticulum inclusion bodies. There was no mutation of the FGFR3 gene and the karotype was normal. These features are of lethal short-limbed platyspondylic dwarfism, Torrance type (OMIM# 151210), an auto-somal dominant condition due to a defect in the COL2A1 gene. This results in a defect in a protein that forms type II collagen that is essential for normal bone development. The risk of recurrence is the same as the general population although there is a theoretical risk of germline mosaicism.