Prenatal Phenotypic Expansion: A Fetus With Neurodegeneration With Developmental Delay, Early Respiratory Failure,...

Neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities (NDDRSB) is an extremely rare but severe disorder. Here, we describe the case of a 24-week-old fetus from a Chinese family with healthy parents. The fetus presented with hydrops fetalis and abnormal limb posturing. Chromosomal microarray analysis revealed that the fetus had a heterozygous 17p12 deletion, which is associated with hereditary neuropathy with liability to pressure palsies. Trio-based exome sequencing (ES) analysis revealed that the deletion was inherited from the father, who has a normal phenotype. Trio-based ES identified a novel nonsense variant (c.229C>T, p.Q77*) and a rare nonsense variant (c.325C>T, p.R109*) in the mediator complex subunit 11 (MED11) gene. Both parents were heterozygous carriers for one of the variants in MED11. This is the first study to report the presence of hydrops fetalis and abnormal limb posturing phenotypes in fetuses with MED11 variants. These results expand the prenatal phenotypic spectrum of NDDRSB, which is helpful for genetic counseling and early prenatal diagnosis of fetuses with ultrasound abnormalities. In addition, the novel c.229C>T variant expands the spectrum of MED11 variants.