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Pathological and neuropathological findings in two males with fragile-X syndrome
1Houndslow & Spelthorne Community and Mental Health Trust, London, UK. mangasaba@aol.com
Insights
Post-mortem examination of two elderly males with fragile-X syndrome revealed characteristic macrocephaly and increased brain weight. Findings suggest cardiac anomalies and cerebellar Purkinje cell loss warrant further investigation in fragile-X syndrome research.
Area of Science:
- Neuropathology
- Cardiology
- Genetics
Background:
- Fragile-X syndrome (FRAXA) is a genetic disorder often associated with intellectual disability and characteristic physical features.
- Post-mortem studies are crucial for understanding the long-term pathological changes in aging individuals with FRAXA.
Observation:
- Two elderly males (67 and 87 years) with FRAXA died from sudden cardiovascular events.
- Both cases exhibited macrocephaly, mitral valve abnormalities, ventricular hypertrophy, and cardiomegaly.
- Autopsies revealed increased brain weight, dilated lateral ventricles, mild hippocampal CA4 pyramidal cell loss, and focal cerebellar Purkinje cell loss.
Findings:
- Neuropathological examination showed no gross neuronal dropout but confirmed focal Purkinje cell loss and gliosis in the cerebellum.
- Interstitial cell hyperplasia was confirmed as the primary cause of megalo-testes in FRAXA.
- The study highlights the need to differentiate aging-related changes from FRAXA-specific neuropathology.
Implications:
- The findings support further research into cardiac anomalies and neuropathological features of fragile-X syndrome.
- Shared features like increased brain weight and Purkinje cell loss may reopen discussions on the relationship between FRAXA and autism.
- Systematic neuropathological studies are urgently needed to fully characterize the brain in aging FRAXA patients.
Abstract:
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.