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Rett syndrome, classical and atypical: genealogical support for common origin
H O Akesson1, B Hagberg, J Wahlström
1Department of Psychiatry, Sahlgrenska University Hospital, Göteborg, Sweden.
Journal of Medical Genetics
|September 1, 1996
Summary
Atypical Rett syndrome (RS) cases, particularly the "forme fruste" (FF) type, are likely true variants of classical RS. Genealogical studies reveal shared ancestry and geographical origins, suggesting a common genetic basis for RS.
Area of Science:
- Genetics
- Neurology
- Pediatrics
Background:
- Rett syndrome (RS) is a complex neurodevelopmental disorder.
- Atypical presentations, such as the
- forme fruste
- (FF) type, require further investigation to understand their relationship to classical RS.
Purpose of the Study:
- To investigate whether atypical RS cases, specifically FF, are true variants of classical RS using genealogical methods.
- To explore the genetic and ancestral links between atypical and classical RS patients.
Main Methods:
- Genealogical analyses were performed on 32 FF RS cases from the Swedish national RS registry.
- Pedigrees of approximately 3200 ancestors were analyzed for geographical origins, ancestry, and consanguinity.
- Comparison with previously identified classical RS patient data.
Main Results:
- Thirty-four percent of FF females traced to a defined "Rett area," with six originating from the same homestead as classical RS patients.
- Four pedigrees showed co-occurrence of FF and classical RS cases, all descending from common ancestors.
- Consanguinity was observed in 6.6% of grandparents, potentially higher than the general Swedish population, supporting findings in classical RS.
Conclusions:
- The findings strongly suggest that many atypical FF cases are genuine variants of classical Rett syndrome.
- Genealogical data support the hypothesis that RS may involve a premutation transmitted over generations, potentially affecting both X chromosomes and autosomes.