Sleep Matters in Children with NF1-Health Care Professionals 

Previous research from 2013 in the US identified that more than 50% of children with NF1 had parent reported sleep disturbances. More recent research from 2021 involving the Drosophila fruit fly has shown that a normally functioning NF1 gene is essential for the regulation of the sleep-wake cycle. However, there has been very little research into the area of Neurofibromatosis Type 1 (NF1) and sleep in patients.

The study, led by Dr Pride and a team of neuropsychologists and sleep experts in Australia, investigated sleep in children with NF1. The NF1 Paediatric Sleep Study aims to characterise the sleep problems seen in children with NF1 and how they impact cognition, behaviour and quality of life.

The researchers focused on sleep and circadian dysregulation in children with NF1 and over 100 children between 6-16 years of age have been evaluated with their results compared to typically developing children. All participants completed comprehensive sleep and medical questionnaires as well as neuropsychological assessment. They also kept sleep diaries and wore accelerometers 24 hours a day for 1 week to track their sleep and daily movements. The researchers examined melatonin secretion and rest–activity rhythms to understand whether circadian processes are disrupted in NF1. Sleep–wake activity was assessed with actigraphy in 104 children with NF1 and 48 controls. In a subset of these children, overnight urine samples were collected to measure 6-sulfatoxymelatonin (aMT6s) as a biomarker of melatonin output.

A wide range of sleep difficulties were found. Poor sleep quality, restless or disturbed sleep and difficulty falling asleep were reported in more than 50% of children with NF1 while frequent night waking's, morning headaches and nightmares were reported in around 20%. The findings revealed a significantly lower overnight melatonin production and differences in circadian rest–activity rhythms in children with NF1 when compared to typically developing children. Children with NF1 showed greater night-to-night variability in sleep timing, reduced sleep efficiency, reduced sleep regularity, a delayed sleep onset and less total sleep time compared to children without NF1. The severity of sleep outcomes also correlated with affected cognitive and emotional functioning, and reduced quality of life.

Children with NF1 were noted to be at an increased risk of insomnia. Overall, more than two thirds of children with NF1 were reported to have significant sleep disturbances indicating that this is a common but under-recognised problem for children with NF1.

Further analysis identified four distinct sleep profiles for children with NF1:

· those that had difficulty falling asleep and later sleep timing,

· those that fell asleep quickly but had greater sleep fragmentation (restlessness),

· those that were considered typical sleepers and

· those with generalised sleep problems affecting multiple aspects of their sleep.

Melatonin appeared altered with decreased urinary melatonin metabolite excretion observed in children with NF1. This could indicate that children with NF1 produce less melatonin or that the timing of melatonin production is different. Interestingly, lower melatonin was associated with a longer sleep onset latency (difficulty falling asleep) in children with NF1 (but not controls). Overall, it is likely that there are multiple biological, psychological and social factors that contribute to the sleep difficulties seen in children with NF1 with concurrent pain, itch, neurodiversity (autism/ADHD) and poor sleep hygiene also identified as factors that can contribute to sleep difficulties.

This study represents the first detailed investigation of sleep using actigraphy and hormonal markers in individuals with NF1. It provides preliminary evidence for altered melatonin secretion as one of the biological factors associated with sleep disturbance. The results highlight the importance of sleep assessment in this group and suggest altered sleep quality and circadian dysregulation are common in NF1 and are related to broader neurodevelopmental challenges. These findings open the door to targeted sleep and circadian interventions as potential strategies to improve outcomes in children with NF1.

Good sleep is essential to brain development and poor sleep can have profoundly negative impacts on learning, behaviour, emotions, day-to-day functioning, family cohesion, mental health and overall well-being. These results pave the way to a greater recognition and understanding of the sleep difficulties faced by children with NF1 and their families. They also lay the groundwork for further research into how to help children with NF1 sleep better. Ongoing research by Dr Pride as part of the REST NF1 Intervention is investigating the role of parent-led behavioural interventions in improving the sleep of children with NF1.

This research study is published in the international peer-reviewed journal ‘Sleep’, you can access the abstract here.

Together with the CTF Support Services Team, Dr Pride is working on an Information Package for parents about sleep issues. She is also about to embark on a pilot clinical trial of a Sleep Intervention Program, so watch this space! Please contact support@ctf.org.au for further information.

Funding information: This work was supported by The U.S. Army Medical Research Material Command and Johns Hopkins University (JHU) via the Neurofibromatosis Therapeutic Acceleration Program with funds provided by a Grant Agreement from Bloomberg Philanthropies. Opinions, interpretations, conclusions and recommendations are those of the interviewee and are not necessarily endorsed by The U.S. Army, Bloomberg Philanthropies or JHU.

You can also help!

Dr Pride and her collaborators are conducting a global survey on NF1 sleep screening and management practices of sleep problems: The Sleep Matters Survey

Who can participate?

This survey is for medical specialists (e.g. neurologist, geneticist, oncologist), allied health professionals or clinical nurse specialists who provide clinical care to individuals with neurofibromatosis type 1 (NF1) through a specialized or multidisciplinary NF1 clinic.

Participation is completely voluntary, all responses are anonymous and it takes approximately 10 minutes to complete. The link below will take you to the study information and consent form and the survey.

What is this survey about?

Your responses will help understand current practices and perspectives to help understand barriers to diagnosis and intervention of sleep problems in NF1.

Please complete this survey so we can understand your perspective! Thank you!

The Sleep Matters Team
Chief Investigator: Dr Natalie Pride, The Children’s Hospital at Westmead, Sydney, Australia. Email: Natalie.pride@health.nsw.gov.au
HREC reference number: 2024/ETH02652

You can read more about Dr Natalie Pride and her research at the "Get to know Australian NF Researchers" Interview here.

If you would like to read the Patients and Carers Summary of this presentation you can view that here.