Genetics and clinical phenotypes of epilepsy associated with Dup15q syndrome

Objective To summarize the genetics and clinical phenotypes of epilepsy in children with Dup 15q syndrome. Methods Twenty patients with Dup 15q syndrome were retrospectively collected, the features of clinical manifestations, electroencephalogram and neuroimaging were analyzed. Results 19 patients had de novo copy number variation (CNV) with a duplication size between 4.87 and 12.9 Mb and 1 patient inherited from mother. The main genes in the region were UBE3A, GABRB3, GABRA5, GABRG3 and HERC2. Age at seizure onset ranged from 3 months to 8 years 4 months (median age: 8 months). Multiple seizure types were observed, included epileptic spasm (85%), focal seizures (70%), tonic seizures (45%) and myoclonic seizures (10%). Developmental delay was presented in all 20 patients. 3 patients had craniofacial anomaly, 1 patient had congenital torticollis and 1 patient had congenital heart disease. 13 patients had Autism-like manifestations. Brain magnetic resonance imaging（MRI）showed enlargement of subarachnoid spaces in the frontotemporal region in 5 patients, deep sulcus in 2 patients, dilated lateral ventricles in 2 patients and agenesis of the corpus callosum in 2 patients. Eight patients were diagnosed with Infantile spasms and three with Lennox-Gastaut syndrome. In the last follow-up, 11 patients were seizure-free for more than 12 months and 9 patients still had seizures. Conclusions Most epilepsy children with Dup15q syndrome had early seizure onset and developmental delay. Seizures can be control in more than half of the patients. Most of them have autism-like manifestations, and some patients have abnormalities in other systems.
Keywords: Dup15q syndrome; Epilepsy; Infantile spasms; Autism; prognosis