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Cited by 34Genetics and Neurodevelopmental DisordersGenomics and Rare DiseasesFetal and Pediatric Neurological Disorders

Severe CNS involvement in WWOX mutations: Description of five new cases

Tabarki, Brahim, AlHashem, Amal, AlShahwan, Saad, Alkuraya, Fowzan S., Gedela, Satyanarayana, Zuccoli, Giulio·2015·American Journal of Medical Genetics Part A
DOI 10.1002/ajmg.a.37363
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Abstract

Recently, mutations in WWOX have been identified in the setting of central nervous system (CNS) disorders, highlighting a previously unrevealed role of this gene in the normal development and function of the CNS. In this report, we add five patients from two seemingly unrelated families presenting with a primarily neurological phenotype. All the children were product of consanguineous marriages. Whole exome sequencing revealed the same homozygous mutation (NM_016373.3:c.606‐1G>A) of WWOX in all five patients. All patients and carriers in the family share the same haplotype indicating the families are in fact related to one another. The clinical presentation included progressive microcephaly, early onset of spasticity in the first 3 months of life, intractable epilepsy, severe failure to thrive, and profound developmental delay. Retinopathy was observed in two patients. All five patients died before their third birthday. Neuroimaging showed extensive neurodegeneration characterized by periventricular white matter volume loss and atrophy of the corpus callosum. Additional degeneration selectively affecting the mediodorsal nucleus of the thalamus was observed in one patient. Our findings in five new patients affected by WWOX mutation with early infantile phenotype confirm the features of the disease represented by early infantile epileptic encephalopathy. We suggest that neuroimaging in these patients reveals a characteristic pattern of neurodegeneration in which the cerebellum is spared that could help with early diagnosis in the appropriate clinical setting. © 2015 Wiley Periodicals, Inc.

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  • Mutations in WWOX are associated with autosomal recessive spinocerebellar ataxia 12, mental retardation, microcephaly, and hypomyelination, among other neurological phenotypes.

    “Mutations in WWOX are associated with autosomal recessive spinocerebellar ataxia 12, mental retardation, microcephaly and hypomyelination164, among other neurological phenotypes.”

    From Imaging structural and functional brain development in early childhood (2018) · cites this paper as [164]

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Authors
Tabarki, B., AlHashem, A., AlShahwan, S., Alkuraya, F. S., Gedela, S., & Zuccoli, G.
Affiliations
  • Riyadh Armed Forces Hospital (SA)
  • Alfaisal University (SA)
  • Nationwide Children's Hospital (US)
  • University of Pittsburgh (US)
Corresponding author
Tabarki, Brahim
ORCID
Venue
American Journal of Medical Genetics Part A
Publisher
Wiley
Published
2015-09-08
Volume
167
Issue
12
Pages
3209-3213
ISSN
  • 1552-4825 (ISSN-L)
  • 1552-4833
DOI
10.1002/ajmg.a.37363
OpenAlex
W2136980073
Cited by
34
References
17
Citations by year
2025: 1 · 2023: 5 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 5 · 2018: 10 · 2017: 2 · 2016: 1 · 2015: 1
FWCI
3.19
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • American Journal of Medical Genetics Part A (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
Keywords
central nervous system involvement, early infantile epileptic encephalopathy, consanguinity, homozygous mutation, microcephaly, spasticity, drug-resistant epilepsy, developmental delay, retinopathy, neurodegeneration, corpus callosum atrophy, mediodorsal thalamus, neuroimaging, early diagnosis
MeSH terms
WW Domain-Containing Oxidoreductase, Female, Homozygote, Humans, Infant, Magnetic Resonance Imaging, Male, Mutation, Oxidoreductases, Pedigree, Phenotype, Prognosis, Spasms, Infantile, Tumor Suppressor Proteins, Aicardi Syndrome, Exome, Neuroimaging

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