InterRett, a model for international data collection in a rare genetic disorder

Area of Science:

• Genetics
• Neurology
• Rare Diseases

Background:

• Rett syndrome (RTT) is a rare neurodevelopmental disorder within the autistic spectrum.
• Existing RTT databases vary in scope and representativeness.
• The InterRett database is a significant international resource for RTT research.

Purpose of the Study:

• To compare the socio-demographic, clinical, and genetic characteristics of the InterRett database with the Australian Rett syndrome database (ARSD).
• To evaluate the strengths and limitations of InterRett against other Rett syndrome studies.
• To assess the suitability of InterRett for investigating genotype-phenotype associations in RTT.

Main Methods:

• Comparative analysis of questionnaire data from InterRett and ARSD.
• Literature review of RTT population-based and case-based studies investigating genotype-phenotype relationships.
• Verification of case status and comparability between the two databases.

Main Results:

• A total of 935 verified RTT cases from InterRett (born after 1976) were compared with 295 ARSD cases.
• InterRett families reported higher education and occupation levels; their children exhibited marginally less severe symptoms.
• The distribution of *MECP2* mutation types was similar across both databases.

Conclusions:

• The InterRett database demonstrates comparability with population-based registries like ARSD.
• InterRett can be confidently utilized for investigating genotype-phenotype associations and clinical variations in Rett syndrome.
• InterRett serves as an exemplary international model for rare disease data collection and research.