Using genetic epidemiology to study Rett syndrome: the design of a case-control study

Citation
H. Leonard et al., Using genetic epidemiology to study Rett syndrome: the design of a case-control study, PAED PERIN, 14(1), 2000, pp. 85-95
Citations number
48
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pediatrics
Journal title
PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
ISSN journal
0269-5022 → ACNP
Volume
14
Issue
1
Year of publication
2000
Pages
85 - 95
Database
ISI
SICI code
0269-5022(200001)14:1<85:UGETSR>2.0.ZU;2-E
Abstract
Rett syndrome is a neurological disorder that is seen almost exclusively in females. Although generally considered to have a genetic basis, the underl ying mechanism remains obscure. One favoured hypothesis is that the syndrom e is an X-linked dominant disorder, lethal or non-expressed in males. Genea logical research has also suggested that the mode of transmission in Rett s yndrome may involve a pre-mutation which over several generations is conver ted to a full mutation. Geographical clustering has been reported, and it h as also been proposed that Rett syndrome is a clinically variable condition and that other neurological disorders may be occurring more commonly in fa milies with Rett syndrome. Other studies have found an apparent increase in intellectual disability and seizures in the extended families of girls wit h Rett syndrome. The science of genetic epidemiology can be used to identif y familial aggregation, which is the clustering of a disorder within a fami ly. We have used a case-control study design to investigate both fetal wast age and familial aggregation of other disorders in families of girls with R ett syndrome. The Australian Rett Syndrome Database provided the source of cases, and control probands were girls of a similar age with normal develop ment. This paper describes the methodology for a case-control study of this rare condition using pedigree data and discusses issues in the collection and evaluation of such data. The use of a control population is an importan t feature. Both the strengths and the shortcomings of our design are identi fied, and recommendations are made for future research.