Gastrointestinal and nutritional problems occur frequently throughout life in girls and women with Rett syndrome.

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) gene 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 female patients with RTT (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%), and biliary tract disorders (3%). Height-for-age, weight-for-age, and body mass index z scores decreased significantly with age; height- and weight-, but not body mass index-for-age z scores were significantly lower in female subjects with MECP2 mutations than in 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 female subjects with MECP2 mutations than in those without. Diagnostic evaluations and therapeutic interventions were used less frequently than the occurrence of symptoms or diagnoses in the RTT cohort. CONCLUSIONS: 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.

Gastrostomy placement improves height and weight gain in girls with Rett syndrome.

BACKGROUND: Growth failure and undernutrition complicate the clinical course of girls with Rett syndrome (RTT). These abnormalities are, in part, the consequence of oral motor dysfunction and inadequate dietary intake. OBJECTIVE: To determine whether gastrostomy placement for nutritional therapy alters the natural history of growth failure and undernutrition in RTT. HYPOTHESIS: We hypothesized that gastrostomy placement for nutritional therapy reverses the decline in height, weight, and body mass index (BMI) z scores in RTT. METHODS: Standard stadiometric and anthropometric measures were obtained to derive height, weight, and BMI z scores and estimates of fat-free mass (FFM) and body fat in a cohort of girls (n = 92) with RTT before and after gastrostomy placement. Methyl-CpG-binding protein 2 (MECP2) mutations and the presence or absence of a fundoplication were recorded. RESULTS: The differences in height (n = 73), weight (n = 81), and BMI (n = 81) z score slopes before and after gastrostomy placement were 1.31 + 2.06 (P < 0.001), 2.38 +/- 3.18 (P < 0.001), and 3.25 +/- 3.32 (P < 0.001), respectively. FFM and body fat (n = 43) increased after gastrostomy by 41 +/- 27 g/cm height (P < 0.001) and 7.5% +/- 5.7% body weight (P < 0.001), respectively. The differences in height, weight, and BMI z score slopes were similar regardless of the age at which the gastrostomy was placed. The differences in height, weight, and BMI z score slopes, as well as the change in FFM and body fat deposition after gastrostomy placement, did not differ between those who did or did not have a fundoplication and among the classes of MECP2 mutations. CONCLUSION: Gastrostomy placement for aggressive nutritional therapy favorably altered the natural history of growth failure and undernutrition in RTT, but did not restore height and weight z scores to birth values, regardless of the age at which surgery occurred and in the presence or absence of a fundoplication.

Bone mineral content and bone mineral density are lower in older than in younger females with Rett syndrome.

Although bone mineral deficits have been identified in Rett syndrome (RTT), the prevalence of low bone mineral density (BMD) and its association with skeletal fractures and scoliosis has not been characterized fully in girls and women with RTT. Accordingly, we measured total body bone mineral content (BMC) and BMD using dual energy x-ray absorptiometry in a cross-sectional group of 50 females, aged 2-38 y, with RTT. Methyl-CpG-binding 2 (MECP2) mutations, skeletal fractures, and scoliosis were documented. The prevalence of BMC and BMD z scores < or-2 SD was 59 and 45%, respectively. Although absolute BMC and BMD increased significantly with increasing age, BMC, and BMD z scores were significantly lower in older than in younger females. The prevalence of fractures and scoliosis was 28 and 64%, respectively. Low BMD z scores were positively associated with fractures and scoliosis. Deficits in BMD were identified across a broad range of MECP2 mutations. This study identified associations among low BMD, fractures, and scoliosis, and underscored the need for better understanding of the molecular mechanisms of MECP2 in the regulation of bone mineral metabolism.

Rett syndrome: North American database.

The International Rett Syndrome Association (IRSA) North American database is the first comprehensive compilation of information in the United States and Canada on individuals with Rett syndrome or with another diagnosis in association with MECP2 mutations. The database contains specific information by diagnosis, mutation status, and mutation type and frequency on 1928 participants. Among the 1928 participants, 85.5% were typical, 13.4% were atypical, and 1.1% had MECP2 mutations but did not have Rett syndrome. MECP2 mutations were identified in 914 of 1059 participants (86%): 799 of 870 (92%) participants with typical Rett syndrome had an MECP2 mutation, 94 of 162 (58%) with atypical Rett syndrome had a mutation, and all 21 individuals diagnosed as Not Rett syndrome had a mutation. Missense-type mutations (39.0%) were slightly more common than nonsense type (35.1%). Individual mutation frequency for the 8 common mutations varied from 11.9% for T158M to 4.4% for R106W; large deletions accounted for 6.4% and C-terminal truncations occurred in 8.8%. The remaining mutations (14.3%) occurred singly or in small numbers. This database provides a unique resource for expanding our understanding of Rett syndrome, for comparison with other national databases, and for future study including organization of clinical trials based on the expected emergence of fundamental therapies.