Gastrointestinal and Nutritional Problems Occur Frequently Throughout Life in Girls and Women With Rett Syndrome

Abstract

Objective We conducted a nationwide survey to determine the prevalence of common gastrointestinal and nutritional disorders in Rett syndrome (RTT) based on parental reporting and related the occurrence of these problems to age and methyl-CpG-binding protein 2 (MECP2) status. Methods We designed a questionnaire that probed symptoms, diagnoses, diagnostic tests, and treatment interventions related to gastrointestinal and nutritional problems in RTT. The International Rett Syndrome Foundation distributed the questionnaire to 1666 family-based members and forwarded their responses for our review. We interrogated the Rare Disease Clinical Research Network database to supplement findings related to medications used to treat gastrointestinal problems in RTT. Results Parents of 983 RTT females (59%) responded and identified symptoms and diagnoses associated with gastrointestinal dysmotility (92%); chewing and swallowing difficulties (81%); weight deficits or excess (47%); growth deficits (45%); low bone mineral content or fractures (37%); biliary tract disorders (3%). Height, weight, and BMI z-scores decreased significantly with age; height and weight, but not BMI, z-scores were significantly lower in females with MECP2 mutations than those without. Vomiting, nighttime awakening, gastroesophageal reflux, chewing difficulty, and choking with feeding were significantly less likely to occur with increasing age. Short stature, low bone mineral content, fractures, and gastrostomy placement were significantly more likely to occur with increasing age. Chewing difficulty, choking with feeding, and nighttime awakening were significantly less likely to occur, whereas short stature was significantly more likely to occur, in females with MECP2 mutations than those without. Diagnostic evaluations and therapeutic interventions were utilized less frequently than the occurrence of symptoms or diagnoses in the RTT cohort. Conclusion Gastrointestinal and nutritional problems perceived by parents are prevalent throughout life in girls and women with RTT and may pose a substantial medical burden for their caregivers. Physician awareness of these features of RTT may improve the health and quality of life of individuals affected with this disorder.

Conceptualizing a quality of life framework for girls with Rett syndrome using qualitative methods

“…Hand function and language skills regress in early childhood, in conjunction with the development of hand stereotypies and impaired mobility [Neul et al, 2010]. These functional deficits are further complicated by the development of comorbid conditions such as epilepsy [Bao et al, 2013], gastrointestinal disorders [Motil et al, 2012], and scoliosis [Downs et al, in press]. Some children can walk, negotiate stairs, self-feed or use eye gaze technology whereas others are unable to walk, require enteral feeding or engage in selfinjurious behaviors.…”

Rett Syndrome: Reaching for Clinical Trials

“…This may be coupled with the appearance of dystonic positions, particularly at the ankles and wrists. Multiple neurologic or systemic issues often arise: 1) epilepsy beginning typically by the third year of life [30][31][32]; 2) periodic breathing consisting of breath-holding or hyperventilation or both [33][34][35]; 3) prominent gastrointestinal (GI) issues from top to bottom, including poor chewing and swallowing, gastroesophageal reflux, delayed stomach emptying, and constipation [36][37][38][39]; 4) decline in growth parameters in most, including height, weight, hands, and feet [28,40]; 5) scoliosis in most with up to 13% requiring surgical correction of the deformity [41]; 6) intolerance of warm temperatures; and 7) cool hands and feet. Ambulation is achieved initially in as many as 80% but is typically broad-based and nonpurposeful.…”

Roles of Methyl-CpG Binding Protein 2 in Immune Function

“…Scoliosis and osteoporosis are prominent (Chahrour and Zoghbi, 2007;Hagberg, 2002;Motil et al, 2014). In addition, gastrointestinal problems are common, including chewing difficulties, gastroesophageal reflux, constipation, and occasional biliary tract disorders (Hagberg, 2002;Motil et al, 2012). These gastrointestinal complications may significantly contribute to the general growth deficit and nutritional deficiencies observed in Rett syndrome patients (Motil et al, 2012).…”

“…In addition, gastrointestinal problems are common, including chewing difficulties, gastroesophageal reflux, constipation, and occasional biliary tract disorders (Hagberg, 2002;Motil et al, 2012). These gastrointestinal complications may significantly contribute to the general growth deficit and nutritional deficiencies observed in Rett syndrome patients (Motil et al, 2012). Autonomic function is also disrupted, including peripheral vascular/vasomotor dysfunction and cardiac abnormalities, with prolonged QT interval and abnormal heart rate representing prominent manifestations of this aspect of disease (Chahrour and Zoghbi, 2007;Ellaway et al, 1999;Glaze, 2005;Hagberg, 2002;Neul et al, 2010;Sekul et al, 1994).…”

“…However, patients with Rett syndrome may suffer from more subtle issues, such as chronic inflammatory disease. Indeed, Rett syndrome patients experience frequent bowel complications (Motil et al, 2012), which in theory could be related to a chronic inflammatory process. Additionally, Rett syndrome patients experience significant bone pathology, including scoliosis and osteopenia (Chahrour and Zoghbi, 2007;Motil et al, 2014).…”