Medical care of adolescents and women with Rett syndrome: An Italian study

Abstract

Rett syndrome (RTT) is a rare neurodevelopmental disorder, linked to MECP2 gene mutations in the majority of cases, which results in severe disability and is associated with several comorbidities. The clinical condition of RTT patients tends to stabilize over time, and prolonged survival has recently been demonstrated. However, limited information is available on the long-term course of older patients with RTT, especially among those in Southern Europe. The aim of our study is to evaluate the main clinical features and state of health of adult Italian patients with RTT and to present their evolution over time, identifying major clinical issues present at different ages. A total of 130 families of patients with RTT aged ≥14 years were asked to complete a questionnaire, 84 of which were returned (65%). Among the clinical characteristics of RTT, stereotypies and poor hand function and feeding ability remained stable over time, while nonverbal communication tended to improve. With regard to the main pathologies, sleep, behavioral, and autonomic disorders persisted into adulthood, while epilepsy improved and musculoskeletal problems worsened. In our sample, older patients with R294X and R133C mutations and with C-terminal deletions showed lower levels of clinical severity. The development of guidelines for the clinical management of patients with RTT will assist health care providers in dealing with the complex RTT phenotype. More extensive data about the long-term course of the condition could help in the design of programs for secondary prevention of disabilities for younger females affected by the syndrome.

Longitudinal course of epilepsy in Rett syndrome and related disorders

“…Over time, both improvement and deterioration occurred, although parents indicated epilepsy stabilized between 20-30 years of life. The Italian cohort included surveys from 84 subjects, 82% of whom had a history of seizures (Vignoli et al, 2012). Seizure onset varied widely from 1 to 16 years, and a high proportion suffered drug-resistant frequent seizures (36%).…”

Twenty years of surveillance in Rett syndrome: what does this tell us?

“…Thus far only two studies conducted in the Netherlands (2007: n = 53, 2012: n = 37) [7] and Italy (n = 84) [8] have specifically examined health in adults with Rett syndrome. Overall, general health was reported to be good.…”

“…Overall, general health was reported to be good. However epilepsy was found to be highly prevalent in both the Dutch (93%) and the Italian cohorts (82%), and while improvement in seizure activity with age was noted for some women [8], some remained difficult to treat and the majority required medications for control of seizures. A post-adolescence decline in gross motor skills has been reported in some [7,9] but not all women with Rett syndrome [7].…”

“…Autonomic dysfunction which may manifest as hyperventilation or breath holding, or peripheral vasomotor disturbances is a well-recognised but poorly understood feature of Rett syndrome. Abnormal or disturbed sleep patterns and behavioural issues also appeared to persist [7,8]. Similarly, gastrointestinal issues such as constipation, reflux, and feeding difficulties remained prevalent [7,8] and may contribute to poor growth [11].…”

“…Abnormal or disturbed sleep patterns and behavioural issues also appeared to persist [7,8]. Similarly, gastrointestinal issues such as constipation, reflux, and feeding difficulties remained prevalent [7,8] and may contribute to poor growth [11]. However, there is a need for replication of these studies using larger sample sizes to improve our understanding of clinical presentations beyond the growth and development of childhood.…”