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Study methodology. Using genetic epidemiology to study Rett syndrome: the design of a case–control study
Author(s) -
Leonard Helen,
Fyfe Susan,
Dye Danielle,
Leonard Seonaid
Publication year - 2000
Publication title -
paediatric and perinatal epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.667
H-Index - 88
eISSN - 1365-3016
pISSN - 0269-5022
DOI - 10.1046/j.1365-3016.2000.00218.x
Subject(s) - rett syndrome , proband , medicine , fragile x syndrome , epidemiology , pediatrics , genetic epidemiology , neurodevelopmental disorder , family aggregation , population , psychiatry , developmental psychology , genetics , mutation , psychology , pathology , biology , environmental health , autism , gene
Rett syndrome is a neurological disorder that is seen almost exclusively in females. Although generally considered to have a genetic basis, the underlying mechanism remains obscure. One favoured hypothesis is that the syndrome is an X‐linked dominant disorder, lethal or non‐expressed in males. Genealogical research has also suggested that the mode of transmission in Rett syndrome may involve a pre‐mutation which over several generations is converted to a full mutation. Geographical clustering has been reported, and it has also been proposed that Rett syndrome is a clinically variable condition and that other neurological disorders may be occurring more commonly in families with Rett syndrome. Other studies have found an apparent increase in intellectual disability and seizures in the extended families of girls with Rett syndrome. The science of genetic epidemiology can be used to identify familial aggregation, which is the clustering of a disorder within a family. We have used a case–control study design to investigate both fetal wastage and familial aggregation of other disorders in families of girls with Rett syndrome. The Australian Rett Syndrome Database provided the source of cases, and control probands were girls of a similar age with normal development. 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 important feature. Both the strengths and the shortcomings of our design are identified, and recommendations are made for future research.