Clinical severity and quality of life in children and adolescents with Rett syndrome.

OBJECTIVE: The clinical features and genetics of Rett syndrome (RTT) have been well studied, but examination of quality of life (QOL) is limited. This study describes the impact of clinical severity on QOL among female children and adolescents with classic RTT. METHODS: Cross-sectional and longitudinal analyses were conducted on data collected from an NIH-sponsored RTT natural history study. More than 200 participants from 5 to 18 years of age with classic RTT finished their 2-year follow-up at the time of analysis. Regression models after adjustment for their MECP2 mutation type and age at enrollment were used to examine the association between clinical status and QOL. RESULTS: Severe clinical impairment was highly associated with poor physical QOL, but worse motor function and earlier age at onset of RTT stereotypies were associated with better psychosocial QOL; conversely, better motor function was associated with poorer psychosocial QOL. CONCLUSIONS: Standard psychosocial QOL assessment for children and adolescents with RTT differs significantly with regard to their motor function severity. As clinical trials in RTT emerge, the Child Health Questionnaire 50 may represent one of the important outcome measures.

Epilepsy and the natural history of Rett syndrome.

BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder primarily seen in females, most with a mutation in MECP2. Epilepsy has been reported in 50%-80%. Previous reports were based on small sample sizes or parent-completed questionnaires, or failed to consider the impact of specific MECP2 mutations. METHODS: The Rare Disease Consortium Research Network for RTT is an NIH-funded project to characterize the clinical spectrum and natural history of RTT in advance of clinical trials. Evaluations include clinical status (classic vs atypical RTT), MECP2 mutations, clinical severity, and presence, frequency, and treatment of seizures. RESULTS: Enrollment as of June 2008 is 602; 528 (88%) meet clinical criteria for classic RTT. Of these, 493 (93%) have MECP2 mutations. Age range was 8 months to 64 years. A total of 360 (60%) were reported to have seizures, including 315 (60%) classic and 45 (61%) atypical RTT. Physician assessment of the 602 indicated that 48% had seizures. There was no significant difference in seizure occurrence by race/ethnicity. A significant age impact for seizures was seen and seizures were infrequent before age 2 years. MECP2 mutations most frequently associated with epilepsy were T158M (74%) and R106W (78%), and less frequently R255X and R306C (both 49%). Individuals with seizures had greater overall clinical severity, and greater impairment of ambulation, hand use, and communication. DISCUSSION: Seizures are common in Rett syndrome, have an age-related onset and occurrence, vary by mutation, and are associated with greater clinical severity. This information represents a key consideration for designing clinical trials.

Colon cleanout preparations in children and adolescents.

To determine the effectiveness and associated side effects of a variety of bowel cleansing preparations before colonoscopy, 52 children, ages 4 months to 18 years, were evaluated. Data gathered included type of cleanout preparation used, adequacy of the preparations, and side effects. Twenty-two combinations of laxatives, lavages, enemas, and rectal suppositories were used. Side effects were reported in 90% of patients. In 79% of the patients the colon was clean or clean with some liquid feces, allowing a complete examination of the colon. Formed feces were present in 21% of the subjects, and cleanout preparations were so inadequate in 9% of the subjects that the procedure had to be rescheduled. The most effective preparations were X-Prep liquid+Adult Fleet enema, GoLYTELY, and GoLYTELY+Adult Fleet enema, all of which allowed a complete examination of the colon. Pediatric Fleet ready-to-use enema was the least effective when used alone. X-Prep liquid+Adult Fleet enema caused the highest number of side effects (18%), while Pediatric Fleet ready-to-use enema alone caused the least (4%). The most effective cleanout preparation with the fewest side effects was GoLYTELY, used alone or in combination with enemas. These results suggest that many typical cleanout preparations yield inadequate results, wasting time or money, and argue in favor of the use of more effective preparations with fewer side effects, such as GoLYTELY.

Oxygen desaturation and cardiac arrhythmias in children during esophagogastroduodenoscopy using conscious sedation.

To determine whether oxygen desaturation and cardiac arrhythmias occur in children during esophagogastroduodenoscopy with the use of conscious sedation, we prospectively studied 34 consecutive patients between the ages of 2 months and 18 years. Patients with pulmonary, cardiac, and neurologic disorders were defined as high risk and those without were defined as normal. All patients received intravenous sedation with meperidine, diazepam, or midazolam, used alone or in combination. Pulse oximetry, respiratory rate, and lead II electrocardiogram were recorded throughout all episodes of desaturation and tachycardia. Oxygen desaturation to less than 90% occurred in 68% of normal patients and in 58% of high-risk patients during esophagogastroduodenoscopy. Seventy-five percent of the high-risk patients and 82% of the normal patients had an arrhythmia during esophagogastroduodenoscopy usually associated with oxygen desaturation. Sinus tachycardia was the most common arrhythmia, although other arrhythmias were identified. Despite the frequency of oxygen desaturation and cardiac arrhythmias, no adverse outcome was observed in any patient. Most episodes of oxygen desaturation and cardiac arrhythmia resolved spontaneously. Subdivision of patients into high-risk groups by age, sex, weight, or diameter of endoscope used did not allow prediction of oxygen desaturation or cardiac arrhythmia. Our data suggest that conscious sedation in children undergoing esophagogastroduodenoscopy is safe and free of significant adverse clinical problems. However, conscious sedation during esophagogastroduodenoscopy continues to have certain inherent risks. Therefore we strongly advocate the routine use of continuous cardiac rhythm and pulse oximetry monitoring of all children during esophagogastroduodenoscopy performed with the use of conscious sedation.

New treatment for rectal impaction in children: an efficacy, comfort, and safety trial of the pulsed-irrigation enhanced-evacuation procedure.

To determine the efficacy, comfort, and safety of the pulsed-irrigation enhanced-evacuation (PIEE) procedure in children, we evaluated 27 procedures performed on 24 consecutive children, 16 boys and 8 girls, 4-15 years old (mean, 8.7), with chronic constipation, encopresis, and rectal impaction. Children with known heart, lung, and/or neurologic diseases were excluded. Temperature, pulse, respiratory rate, and blood pressure were obtained prior to, during, and immediately after the procedure. Abdominal radiographs were obtained before and after the procedure, and the degree of disimpaction was estimated by a single radiologist. Patients graded the discomfort of the procedure at the time of speculum insertion and every 15 min from 1 to 5: 1, painless; 2, mild discomfort; 3, moderate discomfort; 4, severe discomfort; 5, extremely painful. Serum sodium, potassium, chloride, and bicarbonate values were obtained before, immediately after, and 90 min after the procedure and compared by paired Student t analysis. A digital rectal examination confirmed rectal impaction prior to insertion of the speculum. One course of pulsed irrigations was performed, typically lasting 25-30 min. No significant changes in vital signs were found during or after the procedure. In 18 of 23 (78%) procedures, there was at least a 50% emptying of feces from the colon immediately after the procedure. Patients continued to empty their colon up to 12 h later; thus, the procedure effectively disimpacted all patients. In terms of comfort, patients graded the PIEE a 2.6 +/- 0.75 (range, 1-5). Speculum insertion was the most uncomfortable factor and received a 2.7. No child had any indication of water intoxication.(ABSTRACT TRUNCATED AT 250 WORDS)