Lethal Congenital Contracture Syndrome Type 3 in an Isolated Canadian Population

The diagnosis of a genetic etiology for fetal akinesia deformation sequence (FADS) in the prenatal setting is challenging. It is especially difficult in patients from isolated populations in which genetic testing has been limited and the background allelic frequencies are unknown. Lethal congenital contracture syndromes type 3 (LCCS3; OMIM 611369) is a rare autosomal recessive condition caused by biallelic pathogenic variants in the PIP5K1C gene. There are only 13 cases of LCCS3 in the medical literature. We describe three cases sharing a novel variant in PIP5K1C in an isolated Canadian population and provide the first detailed postnatal phenotyping of the condition in live born neonates. The repeatedly observed variant in the PIP5K1C gene and identification of three apparently unrelated cases suggest the possibility of a founder effect in this population. These cases add to our understanding of an ultra-rare genetic condition and provide personalized management in this underserviced population.