Investigators at the Boston Children's Hospital, MA, and other centers evaluated the role of copy number variants (CNVs) detected using chromosomal microarray (CMA) testing in 805 patients seen between 2006 and 2011 and having ICD-9 codes for epilepsy or seizures. They observed 437 CNVs in 323 patients (1-4 per patient), including 185 (42%) deletions and 252 (58%) duplications. Forty (9%) were confirmed de novo, 186 (43%) were inherited, and parental data were unavailable for 211 (48%). CNV size ranged from 18kb to 142Mb (excluding full trisomies), and 34% were >500kb. The epilepsy phenotype was explained by a CNV in at least 40 cases (5%), including 29 patients with epilepsy associated syndromes and 11 with likely disease-associated CNVs involving epilepsy genes or “hotspots” (e.g., 1q21.1, 15q11.2, 16p13.11) that predispose to epilepsy.

Genetic syndromes associated with epilepsy and confirmed by CNV testing included 22q11 duplication (4 cases), Mowat-Wilson (3 cases), Wolf-Hirschhorn (3 cases), Dravet (2), Williams (2), Kleefstra (2), Angelman (2), Phelan-McDermid (2), and benign familial neonatal convulsions, totalling 3.6%. CMA is recommended in the diagnosis of unexplained epilepsy. [1]

COMMENTARY. The advantages of the CNV to the patient with an unexplained epilepsy, parents, and clinician include an earlier more definitive diagnosis, an estimate of prognosis, and in some cases, more specific treatment. Screening for rare CNVs is a valuable routine diagnostic workup in patients with unclassified epilepsies and complex phenotypes; 88 rare CNVs were discovered in 71 of 222 patients (31.9%) [2]. A chromosomal microarray (CMA) screen of 215 patients with a broad range of neurological phenotypes of unknown etiology found 30 (14%) were abnormal; phenotypes included infantile spasms, other epilepsies, and cortical malformations [3].

CMA is recommended especially in unclassified epilepsy patients with dysmorphic features, developmental delay, autistic spectrum disorder, family history of epilepsy, or parental consanguinity. More directed genetic testing for specific epilepsy genes or genetic neurological syndromes is indicated for patients with a characteristic phenotype [4].