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Abstract Details

The Phenotypic Spectrum of Epilepsy in Desanto-Shinawi Syndrome
Child Neurology and Developmental Neurology
P16 - Poster Session 16 (5:30 PM-6:30 PM)
5-015
To clarify the phenotypic spectrum of epilepsy in Desanto-Shinawi syndrome.

WAC encodes WW domain-containing adaptor with Coiled-Coil region. Pathogenic WAC variants cause Desanto-Shinawi syndrome; affected patients have dysmorphic features, developmental impairment and behavioral abnormalities. Seizures have been reported in about 15%, including tonic-clonic, absence, and febrile seizure semiologies.

We reviewed our epilepsy research database for children who had experienced seizures and had pathogenic WAC variants.
We identified three patients, including two siblings. (1) A five-year-old boy presented with seizures before 1 year of age. These occurred from sleep, involving brief crying, left arm stiffening, perioral cyanosis and unresponsiveness. He has language delay. On exam he has relative macrocephaly, bitemporal hirsutism, and other dysmorphic features. (2) His nine-year-old sister was diagnosed with language delay at 16 months of age. She had similar seizures from sleep from 1 to 3 years of age.  She has relative macrocephaly, bitemporal hirsutism, and other dysmorphic features.  Both siblings had normal EEG, microarray and brain MRI.  The sister’s genetic testing identified a heterozygous likely pathogenic truncation variant in WAC (c. 1864 C>T, p.Arg622*) which was subsequently also found in her brother.  The parents tested negative for the variant on DNA samples extracted from blood, suggesting one of them has germline mosaicism. (3) An unrelated 15-year-old young woman has autism, language delay and epilepsy. She had generalized tonic-clonic seizures from sleep beginning at 14 years of age, controlled with lamotrigine.  She had a normal brain MRI and EEG showed right frontal focal epileptiform activity. A gene panel identified an apparently de novo heterozygous pathogenic truncation varient in WAC (c.148 G>T, p.G50X). 
The findings in this small cohort of patients suggest that the course of epilepsy in Desanto-Shinawi syndrome is often relatively benign. Seizure onset may occur from infancy to adolescence. 
Authors/Disclosures
Abdulla Alawadhi, MBBS (Dubai health / AJCH)
PRESENTER 		Dr. Alawadhi has nothing to disclose.
Ken Myers, MD, PhD (Montreal Children'S Hospital/McGill University Health Centre) Dr. Myers has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Myers has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jazz Pharmaceuticals. Dr. Myers has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pendopharm. Dr. Myers has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AS2Bio. The institution of Dr. Myers has received research support from Fonds de Recherche de Santé Québec. The institution of Dr. Myers has received research support from Liam Foundation. The institution of Dr. Myers has received research support from Pediatric Research Foundation. The institution of Dr. Myers has received research support from Montreal Children's Hospital Foundation. The institution of Dr. Myers has received research support from CQDM/Pharma Liam. The institution of Dr. Myers has received research support from CIHR.