Psychotic disorder and focal epilepsy in a left-handed patient with chromosome XYY abnormality

Summary: Psychotic disorder and focal epilepsy in a left-handed patient with chromosome XYY abnormality: Objective: To discuss the relationship between XYY chromosome abnormality, psychiatric disorders and epilepsy. Method: Single case report. Results: A 34-year-old man with 47, XYY karyotype and normal intelligence was followedup at a neuropsychiatrie clinic for over 30 years. He was first seen at age 3 years with a history of delayed motor and language development and an immunodeficiency syndrome. At age 8 years he developed refractory focal epilepsy, and in late adolescence he started to exhibit increasingly prominent obsessive thoughts, paranoid ideation, and aggressive sexual fantasies and behaviour. Conclusions: When interpreted within the context of previous literature reports, this case suggests a pathophysiological link between XYY chromosome abnormality, characteristic psychiatric symptoms and epilepsy disorder. Key-words: XYY chromosome disorder - Psychotic disorder - Epilepsy - Case report. INTRODUCTION XYY syndrome is a rare sex chromosome abnormality (SCA) often associated with language deficits, reduced social skills and psychiatric disorders (12, 14, 17). An altered expression of the genes on the X and/ or Y chromosomes may predispose individuals with SCAs to vulnerability to additional genetic and environmental insults, such as familial psychopathology, abuse, birth trauma and comorbid conditions (15, 18). These insults may subsequently trigger childhood or adult onset of psychotic disorders (15, 18). Sex chromosome abnormalities also alter the development of the physiological asymmetry between brain hemispheres, which is critical for several mental functions and language (6, 8, 9). This is explained by localization of the gene for cerebral asymmetry on the X and Y chromosomes (5, 23), as supported by a sexual dysmorphism in asymmetry (3), greater relative hand skills (right > left) and greater verbal ability in females than in males (5), and non-dominant hemispheric (spatial) deficits in XO individuals and dominant hemispheric (verbal) deficits in XXY and XXX individuals (13). As suggested by some authors, an abnormal brain lateralization may result in language deficits and psychotic disorders (7, 10, 11). For example, schizophrenia and, to a lesser extent, bipolar disorder display widespread cerebral re-organization, including bilateral distribution of language components normally localized on the left hemisphere (7, 20). In this report, we describe the concomitant occurrence of psychotic disorders, focal epilepsy and XYY chromosome abnormality in a 34year-old left handed man. CASE REPORT RG. was bora full term with a normal delivery. Family history was negative for epilepsy and psychiatric disturbances. Early motor and language development was delayed, with first words at 20 months, and first sentences at 30 months (instead of 12-14 and 24 months respectively). At 18 months he had an isolated febrile seizure. His karyotype was found to be 47, XYY. He was referred to our clinic at age 3 years because of IgA and T lymphocyte deficiency, which was considered idiopathic. At age 8 he developed focal motor seizures, mostly nocturnal, without secondary generalization. Seizures persisted with varying frequency (from weekly to about yearly) despite subsequent treatments with phenobarbital (up to 150 mg/day), carbamazepine (up to 800 mg/day) and, currently, oxcarbazepine (900 mg/day). Over the years, his EEG recordings showed a posterior alpha activity reacting normally to eye opening and closure (Fig. 1), with slow abnormalities and, at times, intermittent or repetitive focal spikes, sharp-waves and spike-and-waves predominant over the right frontal-temporal regions. During childhood, the patient was segregated from his peers because of fear of infections due to his immunodeficiency. In elementary school, he displayed difficulties with literacy skills, in particular reading and spelling. …