Genetic and clinical variations in a Norwegian sample diagnosed with Rett syndrome

Area of Science:

• Neuroscience
• Genetics
• Pediatrics

Background:

• Rett syndrome (RTT) is a neurodevelopmental disorder.
• Mutations in the MECP2 gene are the primary cause of RTT.
• Current diagnostic criteria for RTT are clinical, not solely genetic.

Purpose of the Study:

• To correlate genotype and phenotype in RTT.
• To investigate clinical associations in RTT.
• To compare individuals with and without MECP2 mutations.

Main Methods:

• Study included 91 females diagnosed with RTT in Norway.
• Clinical examinations, interviews, and medical record reviews were conducted.
• Exome sequencing identified causative mutations in individuals without known mutations.

Main Results:

• Causative mutations identified in 86 individuals; 77 had MECP2 mutations.
• Nine individuals had mutations in other genes (SMC1A, SYNGAP1, SCN1A, CDKL5, FOXG1, chromosome 13q).
• Significant phenotypic differences observed based on MECP2 genotypic status, affecting development and epilepsy.

Conclusions:

• Considerable genetic and clinical variation exists in RTT.
• MECP2 mutations significantly impact the clinical phenotype of RTT.
• MECP2 is a key determinant of clinical presentation in RTT.