Associations Between Hyperphagia, Symptoms of Sleep Breathing Disorder, Behaviour Difficulties and Caregiver Well-Being in Prader-Willi Syndrome: A Preliminary Study.

Prader-Willi syndrome (PWS) is a rare genetic disorder characterised by neurodevelopmental delays, hyperphagia, difficulties with social communication and challenging behaviours. Individuals require intensive supervision from caregivers which may negatively affect caregiver quality of life. This study used data collected in the Australasian PWS Registry (n = 50, mean age 11.2 years) to evaluate associations between child behaviours and caregiver mental well-being. Symptoms of sleep-related breathing disorder, child depression and social difficulties were associated with poorer caregiver mental and physical well-being. Growth hormone therapy use was associated with better caregiver mental and physical well-being. Optimising management of problematic behaviours and sleep disturbances have the potential to support caregivers who are the most vital network of support for individuals affected by PWS.

Requirements for improving health and well-being of children with Prader-Willi syndrome and their families.

Prader-Willi syndrome (PWS) is a rare genetic condition with multi-system involvement. The literature was reviewed to describe neurodevelopment and the behavioural phenotype, endocrine and metabolic disorders and respiratory and sleep functioning. Implications for child and family quality of life were explored. Challenging behaviours contribute to poorer well-being and quality of life for both the child and caregiver. Recent evidence indicates healthy outcomes of weight and height can be achieved with growth hormone therapy and dietary restriction and should be the current target for all individuals with PWS. Gaps in the literature included therapies to manage challenging behaviours, as well as understanding the effects of growth hormone on respiratory and sleep function. New knowledge regarding the transition of children and families from schooling and paediatric health services to employment, accommodation and adult health services is also needed. Developing a national population-based registry could address these knowledge gaps and inform advocacy for support services that improve the well-being of individuals with PWS and their families.

Respiratory morbidity in Rett syndrome: an observational study.

AIM: Respiratory illness is a major cause of morbidity and mortality in Rett syndrome. This study investigated respiratory morbidity and relationships with age, mutation type, feeding, and walking status. METHOD: Families registered with the InterRett database (n=399) provided data on the health of their child with Rett syndrome (age 2-57y). Hospital admissions because of lower respiratory tract infection (LRTI) over a 5-year exposure period were investigated by age, mutation type, enteral feeding, and walking status. RESULTS: A hospital admission for LRTI over the previous 5 years was reported for slightly more than one-fifth (21.4%) of individuals. Age and mutation groups did not seem to influence hospital admissions for LRTI but there was nearly twice the risk of an admission with enteral feeding (adjusted relative risk 1.79, 95% confidence interval [CI] 1.21-2.65). Compared with independent walking, being unable to walk was associated with a sixfold increased risk (adjusted relative risk 6.73, 95% CI 3.42-13.25), with assisted walking associated with an intermediate risk. INTERPRETATION: Beyond the influence of mutation type, walking seems to have protective effects on respiratory health. Further studies of exercise physiology in Rett syndrome and how this can be influenced by increasing activity levels are indicated. WHAT THIS PAPER ADDS: Rett syndrome is associated with increased vulnerability to lower respiratory tract infection (LRTI) requiring hospitalization. Enteral feeding is associated with a higher risk of hospital admission for LRTI. Assisted walking mitigates the risk of hospital admission for LRTI for those unable to walk independently.

Autonomic breathing abnormalities in Rett syndrome: caregiver perspectives in an international database study.

BACKGROUND: Rett syndrome is a severe neurodevelopmental disorder associated with mutations in the MECP2 gene. Irregular breathing patterns and abdominal bloating are prominent but poorly understood features. Our aims were to characterize the abnormal breathing patterns and abdominal bloating, investigate the distribution of these by age and mutation type and examine their impact and management from a caregiver perspective. METHODS: We invited previously recruited families from the International Rett Syndrome Study to complete a web-based questionnaire concerning their family member with Rett syndrome aged between 2 and 57 years. We used logistic regression to investigate presence, frequency and impact of breath-holding, hyperventilation, or abdominal bloating by age group and mutation type. Age of onset for both breathing abnormalities was investigated using time-to-onset analysis, and the Kaplan-Meier method was used to estimate the failure function for the study sample. Descriptive statistics were used to characterize the management of irregular breathing. RESULTS: Questionnaires were returned by 413/482 (85.7%) families. Breath-holding was reported for 68.8%, hyperventilation for 46.4% and abdominal bloating for 42.4%. Hyperventilation was more prevalent and frequent in those younger than 7 years of age and abdominal bloating in those aged over 20 years. Onset of breathing irregularities usually occurred during early childhood. Caregivers perceived that daily life was considerably impacted for almost half (44.1%) of those with abdominal bloating and in just over than a third of those with breath-holding (35.8%) or hyperventilation (35.1%). Although perceived impact was broadly comparable between age and mutation groups for breath-holding, hyperventilation and abdominal bloating, girls and women with a p.Arg294* mutation were considered to be more affected by all three conditions. Only 31 individuals had received medically prescribed treatments including 12 different medications, added oxygen, rebreathing apparatus or non-invasive ventilation. CONCLUSIONS: Autonomic disturbances are prevalent and burdensome in Rett syndrome. This information may guide the design of inclusion criteria and outcome measures for clinical intervention trials targeting autonomic abnormalities. Further investigation of available treatments is necessary to delineate evidence-based management pathways.