Long-term Follow-up of Gastrointestinal Manifestations in Rett Syndrome - A National Center Experience

Objective: Rett syndrome is a neurodevelopmental disorder characterized by neurological, musculoskeletal and gastrointestinal (GI) manifestations. Data regarding the long- term course of the gastrointestinal involvement is scarce. We aimed to characterize those features in a large national patient population.

Methods: A retrospective cohort study of patients with Rett syndrome followed between 1991-2021 at the national center for Rett patients in Israel. Clinical features during follow-up, laboratory and genetic data were retrieved.

Results: 141 patients were enrolled, of them 139 females. The median age at the first visit was 3.19 years (IQR 2.33-5.74 years), and the median length of follow-up 94.5 months (IQR 28.6-153.3 months). The main gastrointestinal features were constipation (80.9%, 114/141) and chewing/feeding difficulties (36.2%, 51/141). Twenty-eight patients (20%) developed aerophagia and 44 patients (31.2%) developed symptoms compatible with gastroesophageal reflux. A feeding gastrostomy tube was inserted in 13 patients (9.2%), 10 of them with Nissen fundoplication. Continuous anthropometric measurements were calculated at ages 2.5, 7.5, 12.5 and 17.5 years during follow-up. The mean weight, height and BMI Z-scores were - 1.09, -1.03 and -0.56, respectively, at age 2.5 years. During follow-up those parameters deteriorated reaching to Z-scores of -3.95, -3.01 and -1.19 for weight, height and BMI (respectively) at age 17.5 years (P<0.001). No relation was found between the genetic mutations and the clinical manifestations or anthropometric parameters.

Conclusions: Chewing/feeding difficulties and constipation appear in 50-80% of patients with Rett syndrome, and clinical GER in a third of the patients. Anthropometric parameters tend to deteriorate with age.