VP13.07: Prenatal recurrence of artrogryposis

A NEK9 mutation is causing a form of lethal congenital contracture syndrome. It's an autosomal recessive disorder. Characteristic features that can be seen on prenatal ultrasound are fetal akinesia, multiple contractures, shortened long bones, thoracic dysplasia, long hypoplasia and protruding abdomen as reported by J.P. Casey et al (2016) in two Irish travelling families. A 29-year-old woman and her partner, G4P1M0, were referred to our tertiary medical centre in the 13th week of pregnancy with suspicion of bilateral pes equinovarus. The couple had two early miscarriages and a termination of pregnancy because of a compound heterozygous mutation in the NEK9 gene with severe fetal abnormalities. The fetus presented with bilateral pes equinovarus, a fixed position of the upper and lower limbs, clenched hands and no visible movements of joints. A chorionic villus biopsy was performed with a normal result of QF-PCR for the most common genetic disorders, as well as a normal result for the Array. The WES showed a recurrence of the NEK9(protein coding) mutation that had also been found in a previous pregnancy. Both parents are carrier of a genetic defect: c.1871A>G in the NEK9 gene heterozygote maternal, c.329_331del in the NEK gene heterozygote paternal. The couple decided to terminate the pregnancy and a son was born, with fixated joints. Autopsy was not performed. Recurrence risk was estimated at 25%. Initially, the mutations found in both parents were classified as variants of uncertain significance (VUS), therefore they were not eligible for PGD. More recently both mutations have been reclassified as probably pathogens so that the couple now is eligible for PGD. The same NEK9 mutation found by whole-exome sequencing in this case was earlier reported in a previous pregnancy. The prenatal presentation of this specific fetus was different from earlier documented cases. There was no shortening of the long bones nor protruding abdomen.