Neuroimaging manifestations and genetic heterogeneity of Walker-Warburg syndrome in Saudi patients
| Autor: | Kalthoum Tlili-Graiess, Sara Alharbi, Fowzan S. Alkuraya, Amal Alhashem, Fawaz Kashlan |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Pediatrics medicine.medical_specialty Genetic counseling Saudi Arabia Neuroimaging Mannosyltransferases Microphthalmia Genetic Heterogeneity 03 medical and health sciences 0302 clinical medicine Developmental Neuroscience medicine Polymicrogyria Humans Pentosyltransferases Walker–Warburg syndrome Retrospective Studies business.industry Genetic heterogeneity Infant Newborn Macrocephaly Brain Membrane Proteins Walker-Warburg Syndrome General Medicine medicine.disease Nucleotidyltransferases Buphthalmos Schizencephaly Mutation Pediatrics Perinatology and Child Health Female Neurology (clinical) medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Brain and Development. 43:380-388 |
| ISSN: | 0387-7604 |
| Popis: | Background Walker-Warburg syndrome (WWS), an autosomal recessive disease, is the most severe phenotype of congenital muscular dystrophies. Its diagnosis remains primarily clinical and radiological. Identification of its causative variants will assist genetic counseling. We aim to describe genetic and neuroimaging findings of WWS and investigate the correlation between them. Methods We retrospectively reviewed the clinical, genetic and neuroimaging findings of eleven Saudi neonates diagnosed with WWS between April 2012 and December 2018 in a single tertiary care center. Correlation between neuroimaging and genetic findings was investigated. Results All patients had macrocephaly except one who had intrauterine growth restriction. Dysmorphic features were identified in nearly half of the patients. Creatine kinase levels were available in nine patients and were always elevated. Homozygous pathogenic variants were identified in all patients spanning POMT1 (n = 5), TMEM5 (n = 3), ISPD (n = 2) and POMT2 (n = 1) including one patient who had a dual molecular diagnosis of ISPD and PGAP2. On neuroimaging, all patients showed cobblestone cortex, classical infratentorial findings, and hydrocephalus. Other cerebral cortical malformations included subependymal heterotopia, polymicrogyria and open-lip schizencephaly in four, two and one patients, respectively. Buphthalmos and microphthalmia were the most prevalent orbital findings and found in all patients either unilaterally or bilaterally. Conclusion WWS is a genetically heterogeneous disorder among Saudis. The case with an additional PGAP2-related phenotype exemplifies the increased risk of dual autosomal recessive disorders in consanguineous populations. MRI is excellent in demonstrating spectrum of WWS brain and orbital malformations; however, no definite correlation could be found between the MRI findings and the genetic variant. |
| Databáze: | OpenAIRE |
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