ABSTRACT
PURPOSE: Rett syndrome is a rare neurodevelopmental disorder associated with methyl CpG binding protein 2 (MECP2) gene mutations. We aimed to characterize the long-term nutritional and gastrointestinal course of Rett syndrome in a large national patient population. METHODS: We conducted a retrospective cohort study of patients followed during 1991-2021 at a national center for Rett syndrome. The data retrieved included clinical features, laboratory and genetic analyses. Continuous anthropometric measurements were calculated for the closest visit to the median ages: 2.5, 7.5, 12.5 and 17.5 years. Kaplan Meier curves were used to describe the appearance of clinical manifestations during the follow up period. Generalized estimating equation models were used to compare repeated measurements. RESULTS: Included were 141 patients (139 females), the median age at the first visit was 3.2 years (interquartile range [IQR] 2.3-5.7), and the median length of follow-up was 94.5 months (IQR 28.6-153.3). Mean weight, height and BMI Z-scores were -1.09, -1.03 and -0.56, respectively, at median age 2.5 years; and deteriorated to -3.95, -3.01 and -1.19, respectively, at median age 17.5 years (P < 0.001). Gastrointestinal features included constipation (47.5%, 67/141) and chewing/feeding difficulties (20%, 28/141) at presentation; and an additional 47 (33.3%) and 24 (17.0%), respectively, during follow up. Twenty-eight patients (20%) developed aerophagia and 44 (31.2%) gastroesophageal reflux. No relation was found between genetic mutation types and clinical manifestations. GI manifestations were more prevalent in patients with typical form of Rett syndrome. CONCLUSIONS: Anthropometric parameters were shown to deteriorate with age, regardless of the specific genetic mutation. Chewing/feeding difficulties, constipation and gastroesophageal reflux are common in Rett patients.
