Expansion of the phenotype of lateral meningocele syndrome
Open Access
- 6 March 2020
- journal article
- research article
- Published by Wiley in American Journal of Medical Genetics Part A
- Vol. 182 (5), 1259-1262
- https://doi.org/10.1002/ajmg.a.61536
Abstract
Lateral meningocele syndrome (LMS) is due to specific pathogenic variants in the last exon of NOTCH3 gene. Besides the lateral meningoceles, this condition presents with dysmorphic features, short stature, congenital heart defects, and feeding difficulties. Here, we report a girl with neurosensorial hearing loss, severe gastroesophageal reflux disease, congenital heart defects, multiple renal cysts, kyphosis and left‐convex scoliosis, dysmorphic features, and mild developmental delay. Exome sequencing detected the previously unreported de novo loss‐of‐function variant in exon 33 of NOTCH3 p.(Lys2137fs). Following the identification of the gene defect, MRI of the brain and spine revealed temporal encephaloceles, inner ears anomalies, multiple spinal lateral meningoceles, and intra‐ and extra‐dural arachnoid spinal cysts. This case illustrates the power of reverse phenotyping to establish clinical diagnosis and expands the spectrum of clinical manifestations related to LMS to include inner ear abnormalities and multi‐cystic kidney disease.Keywords
Funding Information
- Fondazione Telethon (GSP15001)
This publication has 9 references indexed in Scilit:
- Renewed proliferation in adult mouse cochlea and regeneration of hair cellsNature Communications, 2019
- Aberrant Regulation of Notch3 Signaling Pathway in Polycystic Kidney DiseaseScientific Reports, 2018
- Neurosurgical management in lateral meningocele syndrome: case reportJournal of Neurosurgery: Pediatrics, 2017
- Lateral meningocele (Lehman) syndrome: A child with a novel NOTCH3 mutationAmerican Journal of Medical Genetics Part A, 2016
- Truncating mutations in the last exon of NOTCH3 cause lateral meningocele syndromeAmerican Journal of Medical Genetics Part A, 2014
- ANNOVAR: functional annotation of genetic variants from high-throughput sequencing dataNucleic Acids Research, 2010
- Notch Signaling Regulates the Extent of Hair Cell Regeneration in the Zebrafish Lateral LineJournal of Neuroscience, 2008
- Notch signaling in the development of the inner ear: Lessons from DrosophilaProceedings of the National Academy of Sciences of the United States of America, 2000
- Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementiaNature, 1996