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AN APPROACH TO GENOTYPE-PHENOTYPE CORRELATION IN RETT SYNDROME
Building: Bourbon Cataratas Convention Centre, Foz do Iguaçu
Room: Iguazu II
Date: 2014-05-05 03:00 PM – 03:15 PM
Last modified: 2014-02-09
Abstract
Introduction
Rett Syndrome (RTT) is a genetic disease caused primarily by mutations in MECP2. There are more than 200 MECP2 mutations but 7 recurrent mutations are associated with 70 % of cases. Diagnosis is based on clinical criteria and confirmed by molecular analysis.
Methods
Clinical severity and phenotypic characteristics of patients with a clinical diagnosis of Rett syndrome and MECP2 gene mutations were analyzed using the Rett Syndrome Severity Scale (RSSS). Type of sequence change in MECP2 gene was considered individually.
Results
16 patients (age: 2-19 years) were assessed. The mean RSSS corresponded to the intermediate range of severity, which reflected that the majority of participants were in the moderate severity category. All of the patients in the sample had speech, hand use and gait abnormalities; 81% had sleep irregularities; 69% epilepsy; 50% breathing abnormalities and only 31% suffered scoliosis (which might be related to a young average sample age). Truncating mutations were related to more severe phenotypes of patients with Rett syndrome and the missense mutation T158M mutation and c.820_1193del associated with milder phenotypes.
Conclusions
While it is not possible to establish a genotype-phenotype correlation due to the small number of patients and variability of genotypes in our sample, we can say that the general genotype-phenotype relationships were confirmed. The clinical severity was found to be very variable even between individuals with the same mutation, which may be influenced by X chromosome inactivation.
Rett Syndrome (RTT) is a genetic disease caused primarily by mutations in MECP2. There are more than 200 MECP2 mutations but 7 recurrent mutations are associated with 70 % of cases. Diagnosis is based on clinical criteria and confirmed by molecular analysis.
Methods
Clinical severity and phenotypic characteristics of patients with a clinical diagnosis of Rett syndrome and MECP2 gene mutations were analyzed using the Rett Syndrome Severity Scale (RSSS). Type of sequence change in MECP2 gene was considered individually.
Results
16 patients (age: 2-19 years) were assessed. The mean RSSS corresponded to the intermediate range of severity, which reflected that the majority of participants were in the moderate severity category. All of the patients in the sample had speech, hand use and gait abnormalities; 81% had sleep irregularities; 69% epilepsy; 50% breathing abnormalities and only 31% suffered scoliosis (which might be related to a young average sample age). Truncating mutations were related to more severe phenotypes of patients with Rett syndrome and the missense mutation T158M mutation and c.820_1193del associated with milder phenotypes.
Conclusions
While it is not possible to establish a genotype-phenotype correlation due to the small number of patients and variability of genotypes in our sample, we can say that the general genotype-phenotype relationships were confirmed. The clinical severity was found to be very variable even between individuals with the same mutation, which may be influenced by X chromosome inactivation.
Keywords
Rett syndrome
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