1. Familial NEDD4L variant in periventricular nodular heterotopia and in a fetus with hypokinesia and flexion contractures
- Author
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Britta Müller, Miriam Elbracht, Ute Hehr, Matthias Begemann, Martin Häusler, Petra Holschbach, Ildiko M. Kabat, Ingo Kurth, Michael Mull, and Florian Kraft
- Subjects
0301 basic medicine ,Heterozygote ,Pathology ,medicine.medical_specialty ,Contracture ,Nedd4 Ubiquitin Protein Ligases ,NEDD4L ,Mutation, Missense ,Hypokinesia ,Toe syndactyly ,Clinical Reports ,arthrogryposis ,fetal hypokinesia ,03 medical and health sciences ,0302 clinical medicine ,Periventricular Nodular Heterotopia ,Genetics ,medicine ,Humans ,Missense mutation ,Child ,Molecular Biology ,Genetics (clinical) ,Arthrogryposis ,Fetus ,Clinical Report ,business.industry ,Syndrome ,medicine.disease ,Developmental disorder ,Phenotype ,030104 developmental biology ,periventricular nodular heterotopias ,nanopore sequencing ,Flexion contractures ,Female ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Background Mutations in the HECT domain of NEDD4L have recently been identified in a cohort of eight patients with a syndromic form of bilateral periventricular nodular heterotopia (PVNH) in association with neurodevelopmental delay, cleft palate, and toe syndactyly (PVNH7). Methods Case report based on NGS sequencing. Results Here, we describe a girl with a novel heterozygous NEDD4L missense variant, p.Tyr679His, and characteristic clinical findings, including bilateral periventricular nodular heterotopia, cleft palate and mild toe syndactyly. Molecular testing from peripheral blood identified the healthy father to carry the NEDD4L variant in mosaic state. Notably, a previous pregnancy of the couple had been terminated due to a complex fetal developmental disorder, including hypokinesia and flexion contractures. Upon review, this affected fetus was also shown to carry the familial NEDD4L variant. Conclusion Our findings may suggest a broader spectrum of NEDD4L‐associated phenotypes, including severe prenatal neurodevelopmental manifestations, which might represent yet another genetic form of fetal hypokinesia with flexion contractures.
- Published
- 2018