Lethal multiple pterygium syndrome: A severe phenotype associated with a novel mutation in the nebulin gene.
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.
Department of Human Genetics, Medical Research Institute, University of Alexandria, Egypt. Electronic address: emnasr@kau.edu.sa.
Ebtesam
E
Abdalla
Harry Perkins Institute for Medical Research and Centre for Medical Research, University of Western Australia, Nedlands, WA 6009, Australia.
Gianina
G
Ravenscroft
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Alexandria, Egypt.
Louay
L
Zayed
Harry Perkins Institute for Medical Research and Centre for Medical Research, University of Western Australia, Nedlands, WA 6009, Australia.
Sarah J
SJ
Beecroft
Harry Perkins Institute for Medical Research and Centre for Medical Research, University of Western Australia, Nedlands, WA 6009, Australia.
Nigel G
NG
Laing
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology*; D037881:Aborted Fetus / Q000473:pathology*; D005260:Female; D005865:Gestational Age; D006720:Homozygote; D006801:Humans; D008305:Malignant Hyperthermia / Q000235:genetics* / Q000473:pathology*; D009124:Muscle Proteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D011247:Pregnancy; D011248:Pregnancy Complications; D012868:Skin Abnormalities / Q000235:genetics* / Q000473:pathology*
D009124:Muscle Proteins; C035620:nebulin
Fetal akinesia; Lethal multiple pterygium syndrome; Nebulin gene