Sleep in Down Syndrome

Sleep disorders are common, often overlooked problem in Down syndrome, particularly during childhood. Comorbidities such as congenital heart disease often present early and management of these needs to take priority. However, this can result in the lack of early development of good sleep habits and may also lead to the perception that sleep issues are an expected problem in children with Down syndrome, which do not require intervention. Studies have shown that sleep problems continue to be under-reported by parents of children with Down syndrome, even though conditions such as obstructive sleep apnoea are up to six times more common in this population. Therefore an understanding of the nature of sleep problems in Down syndrome is important for anyone working with this group. In this chapter we provide an overview of this topic, highlighting the key sleep issues encountered by children with Down syndrome, as well as providing a general approach to evaluation and management

Rationale for and design of the "POSTA" study: Evaluation of neurocognitive outcomes after immediate adenotonsillectomy compared to watchful waiting in preschool children

Background: IQ deficits are linked to even mild obstructive sleep apnoea (OSA) in children. Although OSA is commonly first diagnosed in the pre-school age group, a randomised trial is still needed to assess IQ outcomes after adenotonsillectomy in the pre-school age-group. This randomised control trial (RCT) will primarily determine whether adenotonsillectomy improves IQ compared to no adenotonsillectomy after 12 months, in preschool (3–5 year-old) children with mild to moderate OSA. Methods: This protocol is for an ongoing multi-centred RCT with a recruitment target of 210 subjects (105 in each arm). Children age 3–5 years with symptoms of OSA, are recruited through doctor referral, at the point of referral to the Ear Nose and Throat (ENT) services. Screening is initially with a questionnaire (Paediatric Sleep Questionnaire, PSQ) for symptoms of obstructive sleep apnoea (OSA). Where questionnaires are positive (suggestive of OSA) and ENT surgeons recommend them for adenotonsillectomy, they are invited to participate in POSTA. Baseline testing includes neurocognitive testing (IQ and psychometric evaluation with the neuropsychologist blinded to randomisation) and overnight polysomnography (PSG). Where the Obstructive Apnoea-Hypopnea Index (OAHI) from the PSG is <10/h per hour, consent for randomisation is sought; children with severe OSA (OAHI ≥ 10/h) are sent for immediate treatment and excluded from the study. After consent is obtained, participants are randomised to early surgery (within 2 months) or to surgery after a usual wait time of 12 months. Follow-up studies include repeat neurocognitive testing and PSG at 12 (with the waiting list group studied before their surgery) and 24 months after randomisation. Analysis will be by intention to treat. The primary outcome is IQ at 12 months’ follow-up. Discussion: If IQ deficits associated with OSA are reversible 12 months after adenotonsillectomy compared to controls, future clinical practice advise would be to undertake early surgery in young children with OSA. The study could provide data on whether a window of opportunity exists for reversing IQ deficits linked to OSA in the pre-school age-group. Trial registration: Australian and New Zealand Clinical Trials Registration Number ACTRN12611000021976.Karen A. Waters, Jasneek Chawla, Margaret-Anne Harris, Carolyn Dakin, Helen Heussler, Robert Black, Alan Cheng, Hannah Burns, John D. Kennedy and Kurt Lushingto

Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV

Snoring in children

Chronic snoring (≥4 nights per week) is not benign. Otherwise healthy children with chronic snoring and evidence of adenotonsillar hypertrophy can be referred directly for adenotonsillectomy. Snoring childre

Common sleep disorders in children

Sleep disorders are common in children and include both respiratory and non-respiratory causes. An awareness of these conditions is important due to the recognized complications of untreated sleep disorders in childhood. This review provides an overview of common sleep disorders in childhood including an overview of treatment options

Evaluation of infant obstructive sleep apnea

Obstructive sleep apnea in infants is a distinct entity that needs to be considered separately to older children. This review article summarizes risk factors associated with infant obstructive sleep apnea, clinical presentation, evaluation and management options for this condition, which differs somewhat in this younger population

Using continuous overnight pulse oximetry to guide home oxygen therapy in chronic neonatal lung disease

Aim: The aims of this study are: (i) to survey the knowledge of paediatric clinicians using overnight continuous pulse oximetry data to guide management of infants with chronic neonatal lung disease (CNLD); (ii) to assess the ability of paediatric clinicians to interpret overnight continuous pulse oximetry data; and (iii) to describe the overnight oximetry interpretation practices of paediatric respiratory specialists. Methods: Paediatric clinicians from three tertiary teaching hospitals completed an anonymous survey regarding overnight continuous pulse oximetry in chronic neonatal lung disease. Using a modified Delphi technique, paediatric respiratory specialists participated in a concordance exercise and discussions to establish consensus interpretations for 25 oximetry studies. Paediatric clinicians were invited to complete the same exercise as a comparison. Results: Self-rated knowledge from 74 surveyed clinicians was proportional to clinical experience. Twenty paediatric clinicians and nine paediatric respiratory specialists completed the oximetry exercise with scores of 64% (κ = 0.25) and 80% (κ = 0.45), respectively. Individual parameters like a mean peripheral arterial haemoglobin saturation (SpO) below 93% and percentage time spent below SpO 93% correlated poorly with the consensus interpretations. Paediatric respiratory specialists instead relied on visual analysis of SpO waveforms, utilising the frequency and depth of desaturations to guide management. Conclusion: Interpretation of overnight oximetry data is variable amongst both paediatric clinicians and respiratory specialists. This likely reflects inadequate evidence defining clinically significant intermittent hypoxaemia, whether in terms of desaturation duration, frequency or nadir