Assessment and Management of Nutrition and Growth in Rett Syndrome

Objective Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting approximately one in 10,000 female births. The clinical features of RTT are known to impact both patients’ and caretakers’ quality of life (QOL) in RTT. We hypothesized that more severe clinical features would negatively impact caretaker physical QOL but would positively impact caretaker mental QOL. Methods Participants were individuals enrolled in the Rett Natural History Study with a diagnosis of classic RTT. Demographic data, clinical disease features, caretaker QOL, and measures of family function were assessed during clinic visits. The Optum™ SF-36v2® Health Survey was used to assess caretaker physical and mental QOL (higher scores indicate better QOL). Descriptive, univariate, and multivariate analyses were utilized to characterize relationships between child and caretaker characteristics and caretaker QOL. Results Caretaker physical component scores (PCS) were higher than mental component scores (MCS): 52.8 (9.7) versus 44.5 (12.1). No differences were noted between the baseline and 5-year follow-up. In univariate analyses, disease severity was associated with poorer PCS (p=0.006) and improved MCS (p=0.003). Feeding problems were associated with poorer PCS (p=0.007) and poorer MCS (p=0.018). In multivariate analyses, limitations in caretaker personal time and home conflict adversely affected PCS. Feeding problems adversely impacted MCS. Conclusions Caretaker QOL in RTT is similar to that for caretakers in other chronic diseases. Disease characteristics significantly impact QOL, and feeding difficulties may represent an important clinical target for improving both child and caretaker QOL. The stability of QOL scores between baseline and 5-years adds important value.

Section: Discussionmentioning

confidence: 73%

Caretaker Quality of Life in Rett Syndrome: Disorder Features and Psychological Predictors

Killian

Lane

Lee

et al. 2016

“…The standard cutoffs of +/− 2 SD (approximating 2 nd and 98 th percentiles) were used for normative charts and more liberal cutoffs of −1.28 SD (10 th percentile) and −0.67 SD (25 th percentile) on RTT charts were tested, in keeping with recent recommendations. 7 Mutation severity was categorized into mild (R133C, R294X, R306C, and 3' truncations) and severe (T158M, R168X, R255X, and R270X) MECP2 mutations. 19 …”

Section: Methodsmentioning

confidence: 99%

“…4 With increasing recognition of the myriad clinical issues and the need for intense therapeutic approaches, longevity and overall quality of life improved. 5 The predominant morbidity issues include growth, 6 nutrition, 7 scoliosis, 8 seizures, 9 aspiration risk, and gastrointestinal dysfunction (gastroesophageal reflux, delayed gastric emptying, and constipation). 10 Clinical experience suggests that intense physical and occupational therapies reduced development of contractures and skeletal deformities and communication technologies improve engagement.…”

Section: Introductionmentioning

confidence: 99%

The Changing Face of Survival in Rett Syndrome and MECP2-Related Disorders

Tarquinio

Hou

Neul

et al. 2015

Purpose Survival in Rett syndrome (RTT) remains unclear. Although early estimates were grim, more recent data suggest that survival into adulthood is typical. We aimed to define survival in RTT more clearly and identify risk factors for early death. Methods Participants with clinical RTT or Methyl CpG Binding Protein 2 mutations without clinical RTT were recruited through the RTT Natural History study from 2006 to 2015. Clinical details were collected, and survival was determined using the Kaplan-Meier estimator. Risk factors were assessed using Cox proportional hazards models. Results Among 1189 valid participants, 51 died (range 3.9–66.6 years) during the 9-year follow-up period. Those who died included 36 (3.9%) classic RTT females, 5 (5.9%) atypical severe RTT females, 1 (2.4%) non-RTT female, the single atypical severe male, 6 (30%) non-RTT males, and 2 (7.1%) DUP males. All atypical mild RTT females, DUP females and the single classic RTT male remain alive. Most deaths were due to cardiorespiratory issues. Only one died due to severe malnutrition, scoliosis, and extreme frailty. Survival for classic and atypical RTT was greater than 70% at 45 years. Overall severity and several modifiable risk factors, including ambulation, weight, and seizures, were associated with mortality in classic RTT. Conclusions Survival in to the 5th decade is typical in RTT, and death due to extreme frailty has become rare. While the leading cause of death remains cardiorespiratory compromise, many risk factors for early death are modifiable. Intense therapeutic approaches could further improve the prognosis for patients with RTT.

“…Categorization of BMI was based on published recommendations, specific to RTT, regarding overweight and obesity (85 th and 98 th percentiles respectively), and under-nutrition (25 th percentile). 27,28 Categorization of MECP2 mutation based on phenotypic similarities 29,30 was as follows: mild mutations included R133C, R294X, R306C, and 3’ truncations; moderate included T158M and other mutations; and severe included R106W, R168X, R255X, R270X, early truncations, and large deletions. Mutation negative participants were excluded from mutation analysis.…”

Section: Methodsmentioning

confidence: 99%

Pubertal Development in Rett Syndrome Deviates From Typical Females

Killian

Lane

Cutter

et al. 2014

Background Rett syndrome is a unique neurodevelopmental disorder, affecting approximately 1 in 10,000 live female births, most experiencing reduced growth. We characterized pubertal trajectories in females with Rett syndrome. We hypothesized that pubertal trajectory deviates from the general female population with early pubertal onset and delayed menarche. Methods Participants were individuals enrolled in the Rett Syndrome Natural History Study with clinical diagnosis of Rett syndrome or mutations in MECP2. Intervals to thelarche, adrenarche, and menarche were assessed by survival analysis; BMI, mutation type, clinical severity, and pubertal milestone relationships were assessed by log-likelihood test; pathway synchrony (relationship between thelarche, adrenarche, and menarche) was assessed by Chi-squared analysis. Results Compared to the general female population, over 25% initiated puberty early, yet entered menarche later (median age 13.0 years). 19% experienced delayed menarche. Median length of puberty, from thelarche to menarche, was 3.9 years. Higher BMI correlated with earlier thelarche and adrenarche but not menarche; milder mutations correlated with earlier menarche; and milder clinical presentation correlated with earlier thelarche and menarche. Fifty-two percent entered puberty in synchrony, but differing from general population, 15% led with thelarche, and 32% with adrenarche. Conclusions Pubertal trajectories in Rett syndrome differ from general population, entering puberty early and reaching menarche later. BMI affects pubertal timing, but the relationship between specific mutations, clinical presentation, and underlying neuroendocrine pathology is less clear.