Arthrogryposis and pterygia as lethal end manifestations of genetically defined congenital myopathies

In this report, four fetal or perinatal autopsy cases of arthrogryposis were studied by gross morphology, microscopic histopathologic examination, and whole genome sequencing of postmortem DNA. Two stillborn sibling fetuses with arthrogryposis, pterygia, and amyoplasia had compound heterozygous pathogenic variants in NEB. A neonate with a histopathologic diagnosis of nemaline myopathy had a heterozygous de novo pathogenic variant in ACTA1. Another stillborn infant with pterygia and arthrogryposis had a heterozygous de novo likely pathogenic variant in BICD2. These cases demonstrate the utility of whole genome sequencing as the principal diagnostic method of lethal forms of skeletal muscle disorders that present with arthrogryposis and muscle amyoplasia/hypoplasia. Molecular diagnosis provides an opportunity for studying patterns of inheritance and for family counseling concerning future pregnancies.

Source: American Journal of Medical Genetics Part A - December 23, 2017 Category: Genetics & Stem Cells Authors: Atif A. Ahmed, Priya Skaria, Nicole P. Safina, Isabelle Thiffault, Alex Kats, Eugenio Taboada, Sultan Habeebu, Carol Saunders Tags: ORIGINAL ARTICLE Source Type: research