Epilepsy and EEG findings in 18 males with fragile X syndrome.

Of the 24 males identified as having fragile X syndrome in the Northeast Essex screening programme, 25% had epilepsy. Epilepsy in individuals with fragile X syndrome is known to follow a benign course with seizures disappearing before the age of 20. However, half of our sample with a history of epilepsy continued to have seizures after the age of 20. We reviewed the EEG reports of 18 of the 24 individuals (aged between 13 and 63 years) including all six individuals with epilepsy. We had 32 EEG recordings from 18 subjects, with nine people having more than one recording at different points. The EEG showed a definite improvement in only five individuals. Three individuals who had serial recordings (one with epilepsy) showed no significant changes over time and the EEG of one subject with epilepsy deteriorated. The most common abnormal EEG findings were rhythmic theta activity (50%) and a slowing of background activity (28%). There were no characteristic features in the sleep EEGs performed on four subjects. The possible implications of these preliminary findings are discussed.

Pathological and neuropathological findings in two males with fragile-X syndrome.

The present paper addresses post mortem pathological and neuropathological findings in two males with fragile-X syndrome, aged 67 and 87 years. Both subjects died from sudden, unexpected cardiovascular causes, and both showed abnormalities of the mitral valve, ventricular hypertrophy and cardiomegaly. Both cases demonstrated macrocephaly characteristic of the classical Martin-Bell phenotype in FRAXA. There was increased brain weight in both cases: macroscopically, both cerebral and cerebellar hemispheres appeared normal, but dilated lateral ventricles were seen; and microscopic examination of the brain in case 2 showed normal hexalaminar architecture and no gross neuronal dropout. The hippocampus showed mild CA4 pyramidal cell loss and associated gliosis. The cerebellum showed focal Purkinje cell loss and corresponding Bergmann gliosis. Whilst there is a need to delineate the microscopic features of fragile-X syndrome from those of the ageing process, there is an urgent need for more systematic neuropathological studies of fragile-X syndrome; the increased brain weight and Purkinje cell loss in autism and fragile-X syndrome reopens the debate on these two conditions. The case for further research into the cardiac anomalies in fragile-X syndrome is also strengthened by the findings. Finally, the present report confirms the role of interstitial cell hyperplasia as the major cause of megalo-testes in this condition.

Case report: autistic disorder and chromosomal abnormality 46, XX duplication (4) p12-p13.

We report an 18-year-old female with a diagnosis of DSM-IV Autistic Disorder and moderate to severe mental retardation who was discovered to have a previously undescribed chromosomal abnormality 46, XX, duplication (4) p12-p13. We discuss her history and diagnosis, noting that the co-occurrence of her diagnoses have not previously been documented. The report adds to the literature supporting the argument that individuals with autistic spectrum disorders should be re-examined for chromosomal abnormalities.

Fragile-X syndrome in North East Essex: towards systematic screening: clinical selection.

A systematic screening for fragile-X syndrome, using various clinical criteria to preselect for cytogenetic testing, was performed throughout the North East Essex Health District on 1100 people attending three different local services for people with learning disability. The selection procedure used varied from a gestalt impression to head, ear and testis measurement depending on the setting. Fifty-nine males and five females who met the selection criteria went on to have chromosome studies. Of these, 23 males and one female were positive (more than 4% positive cells). They came from 19 families. Whilst the true prevalence of fragile-X syndrome is not known in the district, at a minimum, it contributed 3.2% of the institutionalized males (health authority care), 4.4% of the boys and 2.1% of the girls attending special schools for severe learning disability, 7.9% of the boys attending schools for mild learning disability (Local Education Authority), and 3.5% of men attending the two adult training centres within the district (social services). These figures compare well with the yield from reported surveys in which all individuals without a known diagnosis were tested cytogenetically.