Adult–onset seizure disorder in the 18q deletion syndrome

Abstract

Sirs: Deletion of the long arm of chromosome 18, the 18q deletion or 18q-syndrome (also known as de Grouchy syndrome; OMIM#601808) produces a variable phenotype encompassing learning disability, short stature, variable dysmorphism (microcephaly, mid-facial hypoplasia, prominent antihelix, long tapering fingers) and neurological symptoms and signs (hypotonia, incoordination) [2, 6, 13, 14]. Magnetic resonance brain imaging (MRI) shows white matter abnormalities with incomplete myelination and poor differentiation of grey and white matter [3, 5], ascribed to loss of the myelin basic protein (MBP) gene which lies on 18q, since deletions in which the MBP gene is retained have normal appearing white matter [3, 5]. The condition has been classified with the leukodystrophies [1]. Neuropathological studies have shown, in addition to white matter changes, glial neuronal heterotopias and misplaced neurons in the molecular layer of the cortex, indicating cortical dysgenesis [8, 12]. Nonetheless, seizure disorders have only rarely been described in 18q-syndrome [4, 9–11], mostly in those of childhood onset. As this condition may be unfamiliar to neurologists working with adult patients, we report a patient with 18qsyndrome with complex partial seizures of adult onset. A 29-year-old woman with severe learning disability due to the chromosome 18q deletion was referred with a one-year history of blank spells. Her parents and carers had noticed stereotyped attacks in which she was pale, her head fell back, her eyes rolled or failed to make eye contact, associated with teeth grinding, moaning, slobbering, and sometimes jerking of the right arm. Episodes would last from 30 seconds to 2 minutes, and clustering of attacks was noted. Afterwards she was tired and would sleep for up to two hours. At best, she could go two weeks without the attacks. Her learning disability had been associated with behavioural disorders, specifically autistic behaviours and impulsive aggression. These had been briefly treated with carbamazepine but without benefit and the drug was stopped two years before the onset of the attacks. Only limited neurological examination was possible, showing mild muscular hypotonia, ataxic gait and eversion of the feet. The clinical history was suggestive of complex partial seizures. Only a limited standard EEG was possible, which showed generally low amplitude with excessive diffuse fast activity but no focal epileptic discharges. Photic stimulation had to be abandoned because of patient restlessness although some following response was seen. Hyperventilation was not possible. It was not thought justified to submit the patient to general anaesthesia for the purpose of MRI of the brain.An empirical trial of lamotrigine was given. This was associated with a reduction in the number of attacks, such that she could go several weeks without, and less drowsiness.Although her attacks may have been behavioural in origin, seizures are more likely given both the postictal phenomena and the response to lamotrigine. Although one review of the neurological manifestations of 18q-syndrome stated that “a substantial minority of patients have epilepsy” [6], we have identified few published reports [4, 9–11]. This is in keeping with a review of over 400 different chromosomal imbalances associated with seizures or EEG abnormalities which reported that “seizures have not been well-described in 18q syndrome” [7]. Most reports refer to seizures of childhood onset [4, 9, 11]. Seizure semiology has been variable, including complex partial seizures with prominent autonomic features [9, 10], apnoeic seizures [4, 9], and benign focal seizures [11]. Given the paucity of previous reports, it remains possible that seizures in patients with the 18qsyndrome represent a chance concurrence. It is not known what percentage of learning disabled adults and children with seizures have 18q-syndrome. However, since 18qmay be associated with neuronal migration disorders, seizures may be symptomatic in these cases. The possibility that dysmyelination contributes to epileptogenesis has been suggested [12] but seems less likely, given the near universality of white matter changes in 18qand the paucity of reports of seizures.