Division of Neurology, Department of Pediatrics, Tawam Hospital, Al Ain.
Division of Genetic and Metabolic Disorders, Departments of Pediatrics, Tawam Hospital, Al Ain.
Epileptic Disord. 2018 Oct 1;20(5):401-412. doi: 10.1684/epd.2018.1005.
Mutations in the WWOX gene have been reported in a number of patients with various neurological disorders including spino-cerebellar ataxia, intellectual disability, epilepsy, and epileptic encephalopathy. We aimed to study the clinical, electrographic, and imaging features of two new cases with WWOX mutations and compare them to previously reported cases with WWOX mutations. We assessed two unrelated children from two consanguineous families who had severe neurological disorder including early-onset spastic quadriplegia, profound developmental delay, epilepsy, and West syndrome. Based on whole-exome sequencing, we identified homozygous null mutations in WWOX in both children, and further addressed the genotype-phenotype correlation. In addition, we provide a detailed review of the previously reported cases of WWOX-related neurological disorders and compare them to the children in this report. The findings in this report expand the clinical phenotype associated with WWOX mutations and confirm a well characterised severe central nervous system disorder in association with biallelic null mutations in WWOX. This syndrome consists of profound psychomotor delay, early-onset 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.
已经有报道称，许多患有各种神经疾病的患者存在 WWOX 基因突变，包括脊髓小脑共济失调、智力障碍、癫痫和癫痫性脑病。我们旨在研究两个具有 WWOX 基因突变的新病例的临床、电描记图和影像学特征，并将其与之前报道的具有 WWOX 基因突变的病例进行比较。我们评估了两个来自两个近亲家庭的无关儿童，他们患有严重的神经疾病，包括早发性痉挛性四肢瘫痪、严重的发育迟缓、癫痫和 West 综合征。基于全外显子组测序，我们在两个孩子中均发现了 WWOX 的纯合性缺失突变，并进一步探讨了基因型-表型相关性。此外，我们提供了对之前报道的 WWOX 相关神经疾病病例的详细回顾，并将其与本报告中的儿童进行了比较。本报告中的发现扩展了与 WWOX 突变相关的临床表型，并证实了与 WWOX 双等位基因缺失突变相关的一种特征明确的严重中枢神经系统疾病。该综合征包括严重的精神运动发育迟缓、早发性痉挛性四肢瘫痪和难治性癫痫，包括癫痫性脑病、获得性小头畸形和生长受限。这可能与进行性脑萎缩有关，提示神经退行性变。临床医生识别这种表型有助于早期诊断和适当的遗传咨询。
