Consensus recommendations on sleeping problems in Phelan-McDermid syndrome.

Early onset sleep problems and disorders are very common in individuals with Phelan-McDermid Syndrome (PMS) with rates of up to 90%. These sleep problems and disorders cannot be taken lightly. Not only do they have a major impact on the health, behaviour, functioning and learning opportunities of affected individuals, they can also have detrimental effects on the well-being and resilience of parents and caregivers, ultimately affecting the physical health, mental health and well-being of the whole social system. In this review we aim to understand the types and frequencies of sleeping problems in PMS as the basis for recommendations on their management and treatment and to provide general guidelines for clinicians and practitioners. We conducted an in-depth literature search, summarised findings, and participated in a series of consensus meetings with other consortium members - experts on PMS and stakeholders - to agree on guidelines and recommendations. In parallel, a world-wide survey was created and distributed amongst parents to include their perspective. Our literature search found only four articles specifically focused on sleeping problems in PMS, although some other articles mentioned prevalence and associated factors. Country-specific prevalence rates ranged between 24% and 46%, whereas our parental survey reported 59%. The main problems reported involved difficulty falling asleep and numerous night awakenings, with being restless in sleep, night-time incontinence, and tooth grinding also commonly reported. Only a small number of individuals had undergone a sleep study monitored by a specialist. Bedtime resistance normally decreases with age, but sleep-onset delay, sleep anxiety, parasomnias, problems falling and remaining asleep remain throughout lifespan, with total sleep time improving during adulthood. However, this improvement was also accompanied by a substantial increase in parasomnias. Ultimately, an increase in sleep disorders in children correlates with increased sleep disorders and daytime sleepiness in parents/caregivers. No study to date has focused on the underlying causes of sleeping problems in PMS, but comorbid mental health conditions, somatic causes, or (poly)pharmacy have been proposed as triggers for sleeping disturbances. Currently there is no PMS-specific treatment for sleeping problems, and current recommendations are mostly based on individuals with intellectual disability and/or neurodevelopmental conditions.

Development, behaviour and sensory processing in Marshall-Smith syndrome and Malan syndrome: phenotype comparison in two related syndromes.

BACKGROUND: Ultrarare Marshall-Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross-sectional study, and results are presented with genetic findings. METHODS: Behavioural phenotypes are compared of eight individuals with Marshall-Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long-term follow-up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall-Smith syndrome. RESULTS: Marshall-Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow-up measurement of cognition and adaptive behaviour in Marshall-Smith syndrome shows different individual learning curves over time. CONCLUSIONS: Results show significant between and within syndrome variability. Different NFIX variants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person-environment fit.