{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:03:55Z","timestamp":1788141835608,"version":"build-2803163510"},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,11,21]],"date-time":"2018-11-21T00:00:00Z","timestamp":1542758400000},"content-version":"vor","delay-in-days":51,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epileptic Disorders"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:italic>Aims<\/jats:italic>. Mutations in the <jats:italic>WWOX<\/jats:italic> gene have been reported in a number of patients with various neurological disorders including spino\u2010cerebellar ataxia, intellectual disability, epilepsy, and epileptic encephalopathy. We aimed to study the clinical, electrographic, and imaging features of two new cases with <jats:italic>WWOX<\/jats:italic> mutations and compare them to previously reported cases with <jats:italic>WWOX<\/jats:italic> mutations.<\/jats:p><jats:p><jats:italic>Methods<\/jats:italic>. We assessed two unrelated children from two consanguineous families who had severe neurological disorder including early\u2010onset spastic quadriplegia, profound developmental delay, epilepsy, and West syndrome.<\/jats:p><jats:p><jats:italic>Results<\/jats:italic>. Based on whole\u2010exome sequencing, we identified homozygous null mutations in <jats:italic>WWOX<\/jats:italic> in both children, and further addressed the genotype\u2010phenotype correlation. In addition, we provide a detailed review of the previously reported cases of <jats:italic>WWOX<\/jats:italic>\u2010related neurological disorders and compare them to the children in this report.<\/jats:p><jats:p><jats:italic>Conclusions<\/jats:italic>. The findings in this report expand the clinical phenotype associated with <jats:italic>WWOX<\/jats:italic> mutations and confirm a well characterised severe central nervous system disorder in association with biallelic null mutations in <jats:italic>WWOX.<\/jats:italic> This syndrome consists of profound psychomotor delay, early\u2010onset spastic quadriplegia, and refractory epilepsy including epileptic encephalopathy, acquired microcephaly, and growth restriction. This can be associated with progressive brain atrophy, suggestive of neurodegeneration. Identification of this phenotype by clinicians may help with early diagnosis and appropriate genetic counselling.<\/jats:p>","DOI":"10.1684\/epd.2018.1005","type":"journal-article","created":{"date-parts":[[2019,8,2]],"date-time":"2019-08-02T13:24:29Z","timestamp":1564752269000},"page":"401-412","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["West syndrome, developmental and epileptic encephalopathy, and severe CNS disorder associated with <i>WWOX<\/i> mutations"],"prefix":"10.1002","volume":"20","author":[{"given":"Qudsia","family":"Shaukat","sequence":"first","affiliation":[{"name":"Division of Neurology, Department of Pediatrics, Tawam Hospital, Al Ain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jozef","family":"Hertecant","sequence":"additional","affiliation":[{"name":"Division of Genetic and Metabolic Disorders, Departments of Pediatrics, Tawam Hospital, Al Ain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman W.","family":"El\u2010Hattab","sequence":"additional","affiliation":[{"name":"Division of Genetic and Metabolic Disorders, Departments of Pediatrics, Tawam Hospital, Al Ain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bassam R.","family":"Ali","sequence":"additional","affiliation":[{"name":"Departments of Pathology, College of Medicine and Health Sciences, UAE University, Al Ain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jehan","family":"Suleiman","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Pediatrics, Tawam Hospital, Al Ain"},{"name":"Department of Pediatrics, College of Medicine and Health Sciences UAE University, Al Ain, United Arab 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