We provide the first study of two siblings with a novel autosomal recessive LRP1-related syndrome identified by rapid genome sequencing and overlapping multiple genetic models. The patients presented with respiratory distress, congenital heart defects, hypotonia, dysmorphology, and unique findings, including corneal clouding and ascites. Both siblings had compound heterozygous damaging variants, c.11420G > C (p.Cys3807Ser) and c.12407T > G (p.Val4136Gly) in LRP1, in which segregation analysis helped dismiss additional variants of interest. LRP1 analysis using multiple human/mouse data sets reveals a correlation to patient phenotypes of Peters plus syndrome with additional severe cardiomyopathy and blood vessel development complications linked to neural crest cells.
Keywords: episodic respiratory distress; fetal ascites; hypertelorism; mild fetal ventriculomegaly; patent ductus arteriosus after premature birth; polyhydramnios; postductal coarctation of the aorta; small anterior fontanelle.
© 2022 Mark et al.; Published by Cold Spring Harbor Laboratory Press.