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Summary: Purpose: Mental retardation, facial dysmorphisms, and neurologic and brain abnormalities are features of 6q terminal deletions. Epilepsy is frequently associated with this chromosome abnormality, but electroclinical findings are not well delineated. We report five unrelated patients with 6q terminal deletions and a peculiar clinical, EEG, and neuroradiologic picture of epilepsy, mental retardation, and colpocephaly. Methods: These three male and two female patients underwent general and neurologic examinations, repeated awake and sleep EEGs, and brain magnetic resonance imaging (MRI). A cytogenetic study and fluorescent in situ hybridization (FISH) with chromosome-specific subtelomeric probes were carried out in all cases. Results: All subjects had seizures characterized by vomiting, cyanosis, and head and eye version, with and without loss of consciousness. In four cases, EEGs showed posterior spike-andwave complexes, which were activated by sleep. No patient had status epilepticus or prolonged seizures. Brain MRI revealed colpocephaly and dysgenesis of the corpus callosum and brainstem in four patients; three of them also had hypertrophic massa intermedia. FISH analysis revealed a 6q terminal deletion in all patients, which ranged between 9 Mb (cases 2 and 3) and 16 Mb (case 4). Conclusions: We suggest that epilepsy associated with 6q terminal deletions is a new entity. Patients with dysmorphic features associated with focal occipital epilepsy, colpocephaly, and dysgenesis of the corpus callosum, thalami, and brainstem should be considered candidates for testing for 6q subtelomere deletions. Key Words: 6q Deletion—Epilepsy—EEG— Colpocephaly—Chromosome abnormalities.

Objective To perform an extensive search for genomic rearrangements by microarray-based comparative genomic hybridization in patients with epilepsy. Design Prospective cohort study. Setting Epilepsy centers in Italy. Patients Two hundred seventy-nine patients with unexplained epilepsy, 265 individuals with nonsyndromic mental retardation but no epilepsy, and 246 healthy control subjects were screened by microarray-based comparative genomic hybridization. Main Outcomes Measures Identification of copy number variations (CNVs) and gene enrichment. Results Rare CNVs occurred in 26 patients (9.3%) and 16 healthy control subjects (6.5%) (P = .26). The CNVs identified in patients were larger (P = .03) and showed higher gene content (P = .02) than those in control subjects. The CNVs larger than 1 megabase (P = .002) and including more than 10 genes (P = .005) occurred more frequently in patients than in control subjects. Nine patients (34.6%) among those harboring rare CNVs showed rearrangements associated with emerging microdeletion or microduplication syndromes. Mental retardation and neuropsychiatric features were associated with rare CNVs (P = .004), whereas epilepsy type was not. The CNV rate in patients with epilepsy and mental retardation or neuropsychiatric features is not different from that observed in patients with mental retardation only. Moreover, significant enrichment of genes involved in ion transport was observed within CNVs identified in patients with epilepsy. Conclusions Patients with epilepsy show a significantly increased burden of large, rare, gene-rich CNVs, particularly when associated with mental retardation and neuropsychiatric features. The limited overlap between CNVs observed in the epilepsy group and those observed in the group with mental retardation only as well as the involvement of specific (ion channel) genes indicate a specific association between the identified CNVs and epilepsy. Screening for CNVs should be performed for diagnostic purposes preferentially in patients with epilepsy and mental retardation or neuropsychiatric features.

To the Editor: Although the association between some chromosomal alterations and epilepsy is well known, few chromosomal abnormalities specifically associated with epilepsy are recognized by neurologists (1). We report a patient affected by a de novo apparently balanced translocation involving the long arm of chromosome 4 (4q34) and the short arm of chromosome 9 (9p22). This 10-year-old girl is the third child of nonconsanguineous, healthy parents. An older sister died at birth of unknown causes. The family history was unremarkable except for a grandmother who had rare generalized tonic–clonic seizures during adulthood. The patient was born at term after a normal pregnancy. Growth measurements at birth were normal. Developmental stages were delayed: the patient started to walk at age 14 months and started using single words at age 18 months. When she was 2 years old, she had brief nocturnal episodes of nonmotivated crying associated with extension of the upper limbs and staring, followed by loss of consciousness. Between ages 3 and 5 years, she had clusters of spasms with sudden adduction of the upper limbs and eye deviation to right. At age 7 years, the patient began to have atonic seizures without loss of consciousness. Antiepileptic drugs, used singly or in association, failed to control the epilepsy. At age 9 years, the girl was referred to our clinic. Physical examination revealed hypertelorism, bushy eyebrows, broad nasal bridge, low-set hair, short neck and extremities, abnormal dermatoglyphic pattern, clinodactyly of the fifth finger and syndactyly of the second and third fingers of both hands, syndactyly of the first three toes, diffuse hirsutism, and genu valgum (Fig. 1).