Case reportLethal multiple pterygium syndrome: A severe phenotype associated with a novel mutation in the nebulin gene

- Fetal akinesia deformation sequence is a genetically heterogeneous disorder.
- The nebulin gene is involved in the etiology of lethal multiple pterygium syndrome.
- NEB mutations are associated with a wide spectrum of phenotypic manifestations.
- Next generation sequencing is a valuable tool for the evaluation of fetal akinesia.

Fetal akinesia deformation sequence is a clinically and genetically heterogeneous disorder characterized by a variable combination of fetal akinesia, intrauterine growth restriction, developmental abnormalities such as cystic hygroma, hydrops fetalis, pulmonary hypoplasia, occasional arthrogryposis, and pterygia. The pathogenetic mechanisms of fetal akinesia deformation sequence include neuropathy, muscular disorders, neuromuscular junction disorders, maternal myasthenia gravis, restrictive dermopathy and others. We here report an Egyptian family presenting with recurrent lethal multiple pterygium syndrome. The diagnosis was based on antenatal sonographic demonstration of complete fetal akinesia and a large cystic hygroma with severe limb contractures evident on postmortem examination. Next generation sequencing performed on the second affected fetus identified a novel homozygous essential splice-site variant in the nebulin gene. In conclusion, our report adds further evidence for the involvement of the nebulin gene in the etiology of fetal akinesia deformation sequence/lethal multiple pterygium syndrome.