Metatropic dysplasia in third trimester of pregnancy and a novel causative variant in the TRPV4 gene

Prenatal diagnosis of skeletal dysplasias is particularly difficult for many reasons and differentiating these disorders in the prenatal period can be challenging because they are rare and many of the ultrasound findings are not necessarily pathognomonic for a specific disorder. The diagnosis is often made just after birth or exitus. The prenatal diagnosis of osteochondrodysplasias is based predominantly upon fetal ultrasound findings and it focuses substantially on the possible lethality of the disorder, without always being able to find a specific name for the disorder. Metatropic dysplasia is a rare osteochondrodysplasia due to mutations in the TRPV4 gene: TRPV4 is a cation channel, non-selectively permeable to calcium, encoded by a gene on chromosome 12q24.11; it is widely expressed and involved in many different physiological processes through responses to several different stimuli (physical, chemical, and hormonal) in ciliated epithelial cells. The exact incidence of this disorder is not known, however less than a hundred cases have been reported at present, with only two prenatal reports but without any reference to the molecular test. We describe the first report of molecular diagnosis of metatropic dysplasia carried out in prenatal diagnosis: the molecular testing of the TRPV4 (transient receptor potential cation channel, subfamily V, member 4, MIM *605427) gene in our case, in fact, detected a causative variant, confirming the diagnostic suspicion, which was made possible thanks also to the utilization of MRI and CT scan. In our case different imaging methods together with the close cooperation of a multidisciplinary team and test availability, allowed an accurate diagnosis.