Snoring toddlers with and without obstructive sleep apnoea differed with regard to snoring time, adenoid size and mouth breathing.

AIM: The difficulty of assessing the likelihood of obstructive sleep apnoea (OSA) in children who snore without full-night polysomnography is widely recognised. Our aim was to identify features that were characteristic of two-year-old children with OSA and evaluate whether this information could be used to assess the likelihood of OSA. METHODS: The study was carried out as part of the Child-Sleep Project, a longitudinal birth cohort study of children born at Tampere University Hospital, Finland. This part of the study focused on the children in the cohort who snored and was carried out between 2013 and 2015. The primary outcomes were measured using parental questionnaires, polysomnography and clinical examinations. RESULTS: In total, 52 children participated at a mean age of 27 months (range 23-34). Of these, 32 (44% male) snorers and 20 (70% male) controls. The most significant findings were that children who had OSA demonstrated longer snoring time (P = .003), a greater tendency for mouth breathing (P = .007) and bigger adenoid size (P = .008) than snorers without OSA. CONCLUSION: Snoring time, adenoid tissue size and mouth breathing were important features that identified the likelihood of OSA in snoring toddlers.

Craniofacial and occlusal development in 2.5-year-old children with obstructive sleep apnoea syndrome.

OBJECTIVES: Paediatric obstructive sleep apnoea syndrome (OSAS) is associated with a range of changes in craniofacial and occlusal development. There is, however, little knowledge of how early in life these changes can be found. The aim of the present study was to determine whether changes in dental arch morphology, occlusion, facial profile, tonsil size, breathing habit or body mass index (BMI) can already be found among 2.5-year-old children with OSAS. MATERIALS AND METHODS: Fifty-two children were recruited to the study. Of these, OSAS was diagnosed in 9 children and 18 children did not snore in polysomnography. These two groups were subsequently compared when evaluating polysomnographic, otorhinolaryngological and dental variables. RESULTS: Children with OSAS had narrower inter canine width than non-snoring children (P = 0.032). Furthermore, children with OSAS had larger adenoid size with respect to the nasopharyngeal volume (P = 0.020) and more tendency to mouth breathing (P = 0.002). No statistically significant differences were found when comparing palatine tonsil size, occlusal characteristics, soft tissue profile measurements or BMI. LIMITATIONS: The limitation of the study is the small sample size. CONCLUSION: Children with OSAS had narrower upper inter canine width than non-snoring children at the age of 2.5 years. Larger adenoid size and mouth breathing tendency were also more common among children with OSAS. Further studies with larger sample sizes are needed to determine if other changes in craniofacial and occlusal development can be found in this age group.

Parental reports showed that snoring in infants at three and eight months associated with snoring parents and smoking mothers.

AIM: This prospective study examined the prevalence of snoring during infancy and the prenatal and postnatal risk factors for this condition. METHODS: The study population comprised 1388 infants from the CHILD-SLEEP birth cohort, who were recruited in the Pirkanmaa Hospital District, Finland, between 2011 and 2013. Sleep and background factor questionnaires were filled out prenatally by parents and when the infant was three and eight months old. RESULTS: The prevalence of habitual snoring was 3.2% at the age of three months and 3.0% at eight months, and snoring infants had more sleeping difficulties at those ages, with odds ratios (ORs) of 3.11 and 4.63, respectively. At three months, snoring infants slept for a shorter length of time (p = 0.001) and their sleep was more restless (p = 0.004). In ordinal logistic regression models, parental snoring (adjusted OR = 1.65 and 2.60) and maternal smoking (adjusted OR = 2.21 and 2.17) were significantly associated with infant snoring at three and eight months, while formula feeding and dummy use (adjusted OR = 1.48 and 1.56) were only associated with infant snoring at three months. CONCLUSION: Parental snoring and maternal smoking increased the risk of snoring. Infants who snored also seemed to suffer more from other sleep difficulties.

Noncoding RET variants explain the strong association with Hirschsprung disease in patients without rare coding sequence variant.

The pathogenesis of Hirschsprung disease is complex. Although the RET proto-oncogene is the most frequently affected gene in Hirschsprung disease, rare coding sequence variants explain only a small part of Hirschsprung disease cases. We aimed to assess the genetic background of Hirschsprung disease using a genome-wide association analysis combined with sequencing all RET exons in samples from 105 Hirschsprung disease cases (30 familial and 75 sporadic) and 386 controls. As expected, variants in or near RET showed the strongest overall association with Hirschsprung disease and the most statistically significant association was observed when using a recessive genetic model (rs2435357, NC_000010.10:g.43582056T > C; genotype TT, OR = 17.31, P = 1.462 × 10-21). Previously published associations in variants in SEMA (rs11766001, NC_000007.13:g.84145202A > C; allele C, OR = 2.268, P = 0.009533) and NRG1 (rs4541858, NC_000008.10:g.32410309A > G; allele G, OR = 1.567, P = 0.015; rs7835688, NC_000008.10:g.32411499G > C; allele C, OR = 1.567, P = 0.015) were also replicated in the genome-wide association analysis. Sequencing revealed a total of 12 exonic RET rare variants. Of these, eight amino acid changing rare variants and two frameshift variants caused or possibly caused Hirschsprung disease. Only a minority of the Hirschsprung disease cases (9/30 familial; 7/75 sporadic) carried one of the rare variants. Excluding the rare variant carriers from the genome-wide association analysis did not appreciably change the association of rs2435357 with Hirschsprung disease. We estimate that approximately two thirds of the sporadic cases may be statistically attributed to the recessive action of the common non-coding RET variants. Thus, even though most cases do not carry rare RET variants, combinations of rare variants and the common non-coding RET variant cause the majority of the cases in our population.

Eveningness associates with smoking and sleep problems among pregnant women.

Sleep problems during pregnancy impair maternal health and increase the risk for adverse pregnancy outcome. The circadian preference toward eveningness has been associated with sleep problems in previous studies. Here, we studied whether evening-type women had more sleep problems during their pregnancy, as compared with other chronotypes, in a sample consisting of 1653 pregnant women from the Finnish CHILD-SLEEP Birth Cohort. Chronotype was assessed with a shortened version of the morningness-eveningness questionnaire. Pregnant evening-type women reported more sleep problems, including troubles of falling asleep (OR = 3.4, p < 0.0001), poor sleep quality (OR = 2.9, p < 0.01) and daily tiredness (OR = 3.2, p < 0.0001) than the morning-type women, even after controlling for sleep duration and sleep deprivation. They had higher scores on Epworth Sleepiness Scale (p < 0.05), Basic Nordic Sleep Questionnaire (p < 0.0001) and Global Seasonality Score (p < 0.01) and were also more often smokers, also during pregnancy (p < 0.001) and reported poorer general health (p < 0.001) than the morning-type women. They also reported having had more sleep problems during their childhood (OR = 1.5, p < 0.05) and adolescence (OR = 2.0, p < 0.001) than the morning-type women. Our results indicate that eveningness is associated with more sleep problems and unhealthy life habits during pregnancy.

[Update on Current Care Guideline: Insomnia]. / KÄYPÄ HOITO-SUOSITUS (Päivitystiivistelmä). Unettomuus.

Insomnia symptoms must be differentiated from insomnia disorder. The correct aiagnosis or insomnia aisoraer is important, as insomnia may also be a symptom of many other diseases. Cognitive behavioral methods are recommended as first-line treatment options. Treatment of acute insomnia with hypnotics should not exceed two weeks. In elderly persons adverse effects of hypnotics may exceed their beneficial effects in long-term use. Antidepressive medications acting on the histamine-1 system may be used in very small doses. The new guideline includes e.g. insomnia in pregnant and menopausal women and in cancer patients, and driving issues.

Thymidine kinase 2 defects can cause multi-tissue mtDNA depletion syndrome.

Mitochondrial DNA depletion syndrome (MDS) is a severe recessively inherited disease of childhood. It manifests most often in infancy, is rapidly progressive and leads to early death. MDS is caused by an increasing number of nuclear genes leading to multisystemic or tissue-specific decrease in mitochondrial DNA (mtDNA) copy number. Thymidine kinase 2 (TK2) has been reported to cause a myopathic form of MDS. We report here the clinical, autopsy and molecular genetic findings of rapidly progressive fatal infantile mitochondrial syndrome. All of our seven patients had rapidly progressive myopathy/encephalomyopathy, leading to respiratory failure within the first 3 years of life, with high creatine kinase values and dystrophic changes in the muscle with cytochrome c oxidase-negative fibres. In addition, two patients also had terminal-phase seizures, one had epilepsia partialis continua and one had cortical laminar necrosis. We identified two different homozygous or compound heterozygous mutations in the TK2 gene in all the patients: c.739 C s -> T and c.898 C -> T, leading to p.R172W and p.R225W changes at conserved protein sites. R172W mutation led to myopathy or encephalomyopathy with the onset during the first months of life, and was associated with severe mtDNA depletion in the muscle, brain and liver. Homozygosity for R225W mutation manifested during the second year of life as a myopathy, and showed muscle-specific mtDNA depletion. Both mutations originated from single ancient founders, with Finnish origin and enrichment for the new R172W mutation, and possibly Scandinavian ancestral origin for the R225W. We conclude that TK2 mutations may manifest as infantile-onset fatal myopathy with dystrophic features, but should be considered also in infantile progressive encephalomyopathy with wide-spread mtDNA depletion.