%0 Case Reports
%T Fetal Presentation of Walker-Warburg Syndrome with Compound Heterozygous POMT2 Missense Mutations.
%A Zago S
%A Silvestri E
%A Arcangeli T
%A Calisesi M
%A Romeo C
%A Parmeggiani G
%A Parrini E
%A Cetica V
%A Guerrini R
%A Palicelli A
%A Bonasoni MP
%J Fetal Pediatr Pathol
%V 42
%N 2
%D Apr 2023
%M 36048137
%F 1.412
%R 10.1080/15513815.2022.2116620
%X Background: Walker-Warburg syndrome (WWS) (OMIM #236670) is an autosomal recessive disorder characterized by congenital muscular dystrophy, hydrocephalus, cobblestone lissencephaly, and retinal dysplasia. The main genes involved are: POMT1, POMT2, POMGNT1, FKTN, LARGE1, and FKRP. Case report: We present a fetus with WWS showing at ultrasound severe triventricular hydrocephalus. Pregnancy was legally terminated at 21 weeks +2 days of gestation. In vivo and postmortem magnetic resonance revealed corpus callosum agenesis and cerebellar hypoplasia. Cobblestone lissencephaly was observed at post-mortem. Next generation sequencing (NGS) of 193 genes, performed on fetal DNA extracted from amniocytes, detected two heterozygous mutations in the POMT2 gene. The c.1238G > C p.(Arg413Pro) mutation was paternally inherited and is known to be pathogenic. The c.553G > A p.(Gly185Arg) mutation was maternally inherited and has not been previously described. Conclusion: Compound heterozygous mutations in the POMT2 gene caused a severe cerebral fetal phenotype diagnosed prenatally at midgestation allowing therapeutic pregnancy termination.