Self-limited focal epilepsy and childhood apraxia of speech with WAC pathogenic variants.

Heterozygous pathogenic WAC variants cause Desanto-Shinawi syndrome; affected patients have dysmorphic features, developmental impairment and behavioral abnormalities. Seizures are reported in one quarter, including tonic-clonic, absence, and febrile seizures. This study aimed to better understand the phenotypic spectrum of epilepsy and development in Desanto-Shinawi syndrome. We identified four children with seizures and pathogenic WAC variants, including two siblings. All had global developmental impairment with language affected most severely; two had diagnoses of childhood apraxia of speech and two had autism spectrum disorder. Seizure onset age ranged from six months to 14 years. Seizures always occurred from sleep and were focal impaired awareness with motor features in three patients, with one having bilateral tonic-clonic seizures of suspected focal onset. Two patients had spontaneous seizure resolution without treatment, and the remaining two were well-controlled on monotherapy. EEG was normal in two patients; one had focal right frontal spikes in drowsiness and sleep while the last had independent centrotemporal spikes from both hemispheres, activated in sleep. All patients had heterozygous truncating pathogenic WAC variants, with negative parental testing. The findings in this cohort of patients suggest that epilepsy in Desanto-Shinawi syndrome is usually focal and self-limited, and may fall within the epilepsy-aphasia spectrum.
Competing Interests: Declaration of competing interest Dr. Myers reports research funding support from Citizens United for Research in Epilepsy, Savoy Foundation, Dravet Canada, Fonds de recherche du Québec – Santé, and the Research Institute of the McGill University Health Centre; and is a site principal investigator or sub-investigator for trials sponsored by LivaNova and Biogen. Dr Scheffer serves/has served on the editorial boards of the Annals of Neurology, Neurology and Epileptic Disorders; may accrue future revenue on pending patent WO61/010,176 (filed: 2008): Therapeutic Compound; has a patent for SCN1A testing held by Bionomics Inc and licensed to various diagnostic companies; has a patent molecular diagnostic/theranostic target for benign familial infantile epilepsy (BFIE) [PRRT2] 2,011,904,493 & 2,012,900,190 and PCT/AU2012/001321 (TECH ID:2012–009) with royalties paid. She has served on scientific advisory boards for UCB, Eisai, GlaxoSmithKline, BioMarin, Nutricia, Rogcon and Xenon Pharmaceuticals; has received speaker honoraria from GlaxoSmithKline, UCB, BioMarin, Biocodex and Eisai; has received funding for travel from UCB, Biocodex, GlaxoSmithKline, Biomarin and Eisai; has served as an investigator for Zogenix, Zynerba, Ultragenyx, GW Pharma, UCB, Eisai, Anavex Life Science and Marinus; and has consulted for Zynerba Pharmaceuticals, Atheneum Partners, Ovid Therapeutics and UCB. She receives/has received research support from the National Health and Medical Research Council of Australia, Medical Research Future Fund, Health Research Council of New Zealand, CURE, Australian Epilepsy Research Fund, March of Dimes and NIH/NINDS. The remaining authors have no conflicts of interest.
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