TY - JOUR
T1 - West syndrome, developmental and epileptic encephalopathy, and severe CNS disorder associated with WWOX mutations
AU - Shaukat, Qudsia
AU - Hertecant, Jozef
AU - El-Hattab, Ayman W.
AU - Ali, Bassam R.
AU - Suleiman, Jehan
N1 - Funding Information:
Two unrelated children with early-onset spastic quadriplegia, psychomotor retardation, and WS were evaluated at the paediatric neurology service at Tawam Hospital, Al-Ain, United Arab Emirates. Written informed consent was obtained from both families. This study was approved by Al-Ain Medical Human Research Ethics Committee according to the national regulations (protocol number 13/95-CRD 297/13), and funded by the United Arab Emirates University (grant number 31M135). DNA samples from peripheral blood were extracted for the affected children and their parents at the hospital laboratory, as recommended by the manufacturer. Chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) was performed as a service at Baylor Genetics Laboratory (www.bmgl.com), Texas, USA, according to the generally accepted international standards.
Funding Information:
This study was approved by Al-Ain Medical Human Research Ethics Committee according to the national regulations (protocol number 13/95-CRD 297/13). Both families consented to this publication. The study was funded by the United Arab Emirates University (grant number 31M135). JS received research awards from the National Health and Medical Research Council (NHMRC), Australia. None of the authors have any conflict of interests to declare.
Publisher Copyright:
© 2018 Epileptic Disorders
PY - 2018/10
Y1 - 2018/10
N2 - Aims. 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. Methods. 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. Results. 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. Conclusions. 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.
AB - Aims. 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. Methods. 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. Results. 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. Conclusions. 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.
KW - WWOX
KW - West syndrome
KW - epileptic encephalopathy
KW - intellectual disability
KW - microcephaly
KW - spasticity
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U2 - 10.1684/epd.2018.1005
DO - 10.1684/epd.2018.1005
M3 - Article
C2 - 30361190
AN - SCOPUS:85055637629
SN - 1294-9361
VL - 20
SP - 401
EP - 412
JO - Epileptic Disorders
JF - Epileptic Disorders
IS - 5
ER -