Background: Rett syndrome (RTT) is an X-linked dominant neurodegenerative disorder with various MECP2 mutations. RTT is one of the most common causes of severe intellectual and complex disability in girls. Therefore, the aims of the study were as follows: to highlight the clinical manifestations of RTT; to present the genotype-phenotype relationship; and to assess the possible relation between severity score, clinical manifestations, and MECP2 gene mutations.
Patients and methods: The present cross-sectional study included 15 girls with typical RTT, diagnosed according to the international criteria of RTT. All included patients were followed up at the pediatric neurology clinic, Cairo University Specialized Pediatric Hospital. They were subjected to screening of the entire coding region of the MECP2 gene (MECP2A and MECP2B) using denaturing high-performance liquid chromatography. The clinical severity was assessed among RTT cases using the International Scoring System.
Results: Stereotypic hand movements were present in all cases, acquired microcephaly was present in 73.3% of cases, autistic features in 66.7% of cases, recurrent seizures in 53.3% of cases, delayed language development in 46.6% of cases, deterioration of speech in 53.3% of cases, and growth retardation and peripheral vasomotor changes in 46.6% of cases. Positive mutations were detected in 10 cases (66.66%): heterozygous for p.R270X mutation (three cases), heterozygous for p.R255X mutation (three cases), and heterozygous for p.R168X nonsense mutation (four cases). Microcephaly, seizures, growth retardation, and autistic features were more frequent in patients with a mutated gene; it was also observed that walking ability was more frequent in patients without a mutation.; thus, genotype-phenotype relationship was confirmed. The relationship between severity score and MECP2 mutation was detected in three cases with severe RTT, but there was no relationship between the severity score and specific MECP2 mutation. There was a relationship between the severity score and the clinical manifestations of RTT.
Conclusion: Mutations of MECP2 analysis were detected in 66.7% of RTT cases. There were relationships between the severity score, clinical manifestations, and MECP2 gene mutations. However, there was no relationship between the severity score and specific MECP2 gene mutation.