Rett Syndrome: Prevalence Among Chinese and a Comparison of MECP2 Mutations of Classic Rett Syndrome With Other Neurodevelopmental Disorders

Abstract

Rett syndrome is an X-linked dominant neurodevelopmental disorder. Mutation of the methyl-CpG-binding protein 2 gene (MECP2) is present in up to 96% of patients with Rett syndrome. Eight mutations represent the hotspot of MECP2 mutations (R106W, R133C, T158M, R168X, R255X, R270X, R294X, and R306C) in patients with classic Rett syndrome. The prevalence and survival rate of Rett syndrome among Chinese women was investigated. The 8 hotspot mutations and the A140V mutation were also studied in 4 cohorts of Chinese children (n = 144) actively followed up in our university neurodevelopmental center with classic Rett syndrome (n = 5), autism spectrum disorder (n = 94), epileptic encephalopathy of unknown cause (n = 22), and nonsyndromal mental retardation (n = 23). The prevalence of Rett syndrome among female Chinese younger than 35 years in Hong Kong West is 0.57 (95% confidence interval, 0.15-0.98) per 10 000. Survival is 100.0% at 10 years and 87.5% at 25 years. Three hotspot mutations (R106W, R255X, and R306C) were found in 3 girls with classic Rett syndrome. No hotspot MECP2 mutations were found in the other 3 cohorts. Screening of MECP2 mutations is not worthwhile in Chinese children with pure cognitive, autistic, or unexplained epileptic disorders without other signs of Rett syndrome. In the early stage of developmental arrest before developmental regression, MECP2 screening might be useful for girls with unexplained epileptic encephalopathy before full-blown classic Rett syndrome is evident.

Trends in the Diagnosis of Rett Syndrome in Australia

“…Cases were usually ascertained through a single contact with specialists (14-18, 25, 27), child health departments (22, 23, 28) or education departments(15, 27), institutions (14, 25) and special schools(14, 15, 24, 26), although some used population-based sources (19-21). In one study, case ascertainment involved contacting laboratories for MECP2 positive individuals or analysis of pre-collected blood from a family RTT organization (13), and only cases with a pathogenic MECP2 mutation were included.…”

“…Recent studies (20, 27) varied in their ascertainment methods, inclusion criteria, measures of frequency, sample size and methods of analysis, making comparisons difficult. For example exclusion of mutation negative (13) or atypical cases (27) could partly explain why the prevalence in France (0.58 per 10,000 females aged 4-15 years) (13) and Hong Kong (0.57 per 10,000 females 35 years or younger) (27) were only two thirds that in Australia (0.88 per 10,000 females aged 5-18 years) (20). …”

Epidemiology of Rett Syndrome in Serbia: Prevalence, Incidence and Survival

“…The prevalence of RTT in 1.19/10,000 in females younger than 18 years registered in Serbia is similar to that observed in Scotland and Sweden [5,24], which is higher than in those registered in the USA (Texas, North Dacota), Japan, Estonia, Switzerland and Hong Kong [6,7,8,9,10,25], and lower than in regions of Norway and Northern Italy [11,26]. …”

“…Survival rate analysis showed that 89% of Serbian RTT patients survive up to 12 years of age, while in Texas the survival rate among the 20 year olds was 94% [12]. Additionally, in Hong Kong, there were no lethal outcomes before the age of 10 in RTT population [25]. …”

Skin injuries and joint contractures of the upper extremities in Rett syndrome

“…), while it was reported as 0.58 per 10 000 mutation‐negative females in France (Bienvenu et al . ) and 0.57 per 10 000 females in atypical cases in Hong Kong (Wong & Li ). Generally, after a period of normal development, a healthy‐looking baby girl falls into developmental stagnation, which is followed by rapid deterioration, loss of acquired speech and the replacement of the purposeful use of hands with incessant stereotypies, a characteristic of the syndrome (Chahrour & Zoghbi ).…”