EP18.45: Prenatal diagnosis, phenotype expansion and genetic analysis of Joubert syndrome with new MKS1 mutation

Pathogenic variants in the MKS1 gene are responsible for a ciliopathy with a wide spectrum of clinical manifestations ranging from Meckel and Joubert syndrome to Bardet-Biedl syndrome, and involving the central nervous system, liver, kidney, skeleton, and retina. Joubert syndrome is an autosomal recessive disorders characterised by the typic neurosonographic “molar tooth" sign, and accompanying neurologic symptoms. Several variants in MKS1 mutation are associated specifically with Joubert syndrome 28 (JBTS28), which is a relatively mild form of the disease, but the MKS1:c.371G>A variant has not been reported in the literature in individuals with MKS1-related diseases. The aim of this case report is to describe the significant ultrasound features of a fetus with JBTS and the genetic analysis of the fetus and parents. We report on a Joubert syndrome fetus at 20 week, with an inherited compound heterozygous mutation in MKS1:c.371G>A, p.Arg124Gln and MKS1:c.76_80+8del. The former mutation was carried by the mother, the latter by the father. This is the first case of Joubert syndrome prenatal diagnosis in a fetus presenting “molar tooth sign” with MKS1:c.371 variant. The fetus also showed other significant structural malformations such as occipital encephalocele, callosal hyperplasia, hypertelorism, polydactily, unilateral microophtalmie and unilateral supernumerary thoracic rib. The discovered microophtalmie and rib anomaly as far as we know are the first prenatally detected features in Joubert syndrome. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.