Mary Anne Tablizo’s research while affiliated with Palo Alto Medical Foundation and other places

Background Joubert syndrome (JS) is an autosomal recessive disorder with a distinctive mid-hindbrain malformation known as the “molar tooth sign” which involves the breathing control center and its connections with other structures. Literature has reported significant respiratory abnormalities which included hyperpnea interspersed with apneic episodes during wakefulness. Larger-scale studies looking at polysomnographic findings or subjective reports of sleep problems in this population have not yet been published. Objectives The primary objectives were (1) compare a large group of children with JS and their unaffected siblings for caregiver-reported sleep difficulties. Secondary objectives were (1) present new polysomnography (PSG) data on our JS cohort; (2) review sleep disordered breathing (SDB) in other rare congenital hindbrain anatomic abnormalities. Design We conducted a cross-sectional study on a cohort of 109 families affected by JS. Methods Pediatric Sleep Questionnaire (PSQ) and the Children’s Sleep Habits Questionnaire (CSHQ) along with general medical health information focused on respiratory and sleep problems were mailed to all patients and families. Caregivers were asked to complete the survey for both children with JS and unaffected siblings, if any. Baseline diagnostic PSG was retrospectively reviewed for those with available studies, and the sleep parameters were compared to a referent cohort. Results Study participants with JS were older than their unaffected siblings (p = 0.02). Genetic mutations were available for 41 out of 118 individuals, with the most common mutation being MKS3 (31.4%). Patients with JS had higher scores in the PSQ compared to their unaffected siblings (p < 0.001). PSG data showed severe SDB with apnea-hypopnea index (AHI) of 23 ± 15 events/h in patients with JS. Events were primarily obstructive (obstructive AHI 18 ± 15 events/h vs central AHI 4 ± 4 events/h). Abnormal sleep architecture with increased arousal indices, decreased efficiency, and more time awake and in light sleep or wakefulness when compared to the referent data. Conclusion SDB is common and severe in patients with JS, and the significantly greater obstructive component reported in this cohort makes it necessary to perform complete PSG studies to address or prevent clinical manifestations in this at-risk population. PSQ could represent a viable method to screen for SDB in JS.

Introduction: Children born prematurely (<37 weeks’ gestation) are at increased risk of perinatal complications, comorbidities, and iron deficiency. Iron deficiency is associated with restless legs syndrome and periodic limb movement disorder. In this study, we assessed the prevalence of restless sleep disorder (RSD) and elevated periodic limb movements during sleep (PLMS) in children born prematurely who underwent polysomnography. Methods: A retrospective chart review of sleep studies was conducted in children aged 1–18 years (median age 4 years) with a history of premature birth. Children with genetic syndrome, airway surgery, or tracheostomy were excluded. Three groups were compared: children with PLMS index >5, children with RSD, and children with neither elevated PLMS index nor RSD. Results: During the study, 2577 sleep studies were reviewed. Ninety-two studies fit our criteria and were included in the analysis. The median age at birth was 31 weeks, and the interquartile range (IQR) was 27–34 weeks. A total of 32 (34.8%) children were referred for restless sleep and 55 (59.8%) for snoring. After polysomnography, 18% were found to have a PLMS index >5/h, and 14% fit the criteria for restless sleep disorder (RSD). There were no statistically significant differences in PSG parameters among the children with RSD, PLMS, and the remaining group, except for lower obstructive apnea/hypopnea index (Kruskal–Wallis ANOVA 8.621, p = 0.0135) in the RSD group (median 0.7, IQR 0.3–0.9) than in the PLMS (median 1.7, IQR 0.7–3.5) or the non-RSD/non-PLMS (median 2.0, IQR 0.8–4.5) groups. Conclusions: There was an elevated frequency of RSD and elevated PLMS in our cohort of children born prematurely. Children born prematurely are at higher risk of iron deficiency which can be a contributor factor to sleep -related movement disorders. These results add new knowledge regarding the prevalence of RSD and PLMS in these children.

Children with Down syndrome (DS) are at high risk of sleep-disordered breathing (SDB). The American Academy of Pediatrics recommends a polysomnogram (PSG) in children with DS prior to the age of 4. This retrospective study examined the frequency of SDB, gas exchange abnormalities, co-morbidities, and surgical management in children with DS aged 2–4 years old at Seattle Children’s Hospital from 2015–2021. A total of 153 children underwent PSG, with 75 meeting the inclusion criteria. The mean age was 3.03 years (SD 0.805), 56% were male, and 54.7% were Caucasian. Comorbidities included (n, %): cardiac (43, 57.3%), dysphagia or aspiration (24, 32.0%), prematurity (17, 22.7%), pulmonary (16, 21.3%), immune dysfunction (2, 2.7%), and hypothyroidism (23, 30.7%). PSG parameter data collected included (mean, SD): obstructive AHI (7.9, 9.4) and central AHI (2.4, 2.4). In total, 94.7% met the criteria for pediatric OSA, 9.5% met the criteria for central apnea, and 9.5% met the criteria for hypoventilation. Only one child met the criteria for hypoxemia. Overall, 60% had surgical intervention, with 88.9% of these being adenotonsillectomy. There was no statistically significant difference in the frequency of OSA at different ages. Children aged 2–4 years with DS have a high frequency of OSA. The most commonly encountered co-morbidities were cardiac and swallowing dysfunction. Among those with OSA, more than half underwent surgical intervention, with improvements in their obstructive apnea hypopnea index, total apnea hypopnea index, oxygen saturation nadir, oxygen desaturation index, total arousal index, and total sleep duration. This highlights the importance of early diagnosis and appropriate treatment. Our study also suggests that adenotonsillar hypertrophy is still a large contributor to upper airway obstruction in this age group.

Exogenous melatonin is typically used for sleep regulation in the context of insomnia either in healthy children or those with neurodevelopmental disabilities. It is also used for the management of circadian rhythm sleep disorders in pediatric and adolescent patients. There are also many other possible indications that we will discuss in this paper beyond the role of melatonin for sleep regulation, including its potential use for various areas of medicine such as inflammatory conditions. Since melatonin is unregulated in the United States, distributed over the counter and perceived to be natural and safe, it has become available in many forms in the last two decades. With increasing sleep disturbances and mental health problems after the COVID-19 pandemic, melatonin has become even more popular and studies have shown a dramatic increase in use as well as resulting side effects, including melatonin overdose. As melatonin is generally viewed by physicians as a benign medication, we hope to increase awareness of melatonin’s properties as well as negative side effects to optimize its use in the pediatric population.

Background: Laryngeal coccidioidomycosis is a rare but life-threatening manifestation of coccidioidomycosis. Data in children are sparse and limited to case reports. We conducted this study to review the characteristics of laryngeal coccidioidomycosis in children. Methods: We performed a retrospective review of patients ≤21 years of age with laryngeal coccidioidomycosis who were treated from January 2010 to December 2017. We collected demographic data, clinical and laboratory studies and patient outcomes. Results: Five cases of pediatric laryngeal coccidioidomycosis were reviewed. All children were Hispanic and 3 were female. The median age was 1.8 years and the median duration of symptoms before diagnosis was 24 days. The most common symptoms included fever (100%), stridor (60%), cough (100%) and vocal changes (40%). Airway obstruction requiring tracheostomy and/or intubation for airway management was present in 80%. The most frequent location of lesions was the subglottic area. Coccidioidomycosis complement fixation titers were frequently low and culture/histopathology of laryngeal tissue was necessary to make a definitive diagnosis. All patients required surgical debridement and were treated with antifungal agents. None of the patients had recurrence during the follow-up period. Conclusions: This study suggests that laryngeal coccidioidomycosis in children presents with refractory stridor or dysphonia and severe airway obstruction. Favorable outcomes can be achieved with a comprehensive diagnostic work-up and aggressive surgical and medical management. With the rise in cases of coccidioidomycosis, physicians should have a heightened awareness regarding the possibility of laryngeal coccidioidomycosis when encountering children who have visited or reside in endemic areas with stridor or dysphonia.

Obstructive sleep apnea (OSA) is described as intermittent partial or complete upper airway obstruction that can disrupt respiratory and ventilatory patterns during sleep [...]

Obstructive sleep apnea (OSA) and asthma are two of the most prevalent and commonly co-existing respiratory conditions seen in the pediatric population. Studies linking asthma and OSA in children are limited but indicate that there is a bi-directional relationship between them with significant overlap in the symptoms, risk factors, pathophysiology, comorbidities, and management. It is suggested that there is a reciprocal association between asthma predisposing to OSA, and OSA worsening symptom control and outcomes from asthma. It stands to reason that inflammation in the upper and/or lower airways can influence each other. Most of the pediatric literature that is available evaluates each aspect of this relationship independently such as risk factors, mechanisms, and treatment indications. This article highlights the relationship between OSA and asthma in the context of shared risk factors, pathophysiology, and available management recommendations in the pediatric population. Early recognition of the co-existence and association between OSA and asthma could ideally improve the treatment outcomes for these two conditions. Gaining a better understanding of the mechanism of this relationship can help identify nuances for medical management, optimize treatment and protect this population at risk from associated morbidity.

Obstructive sleep apnea (OSA) is a clinical disorder within the spectrum of sleep-related breathing disorders (SRDB) which is used to describe abnormal breathing during sleep resulting in gas exchange abnormalities and/or sleep disruption. OSA is a highly prevalent disorder with associated sequelae across multiple physical domains, overlapping with other chronic diseases, affecting development in children as well as increased health care utilization. More precise and personalized approaches are required to treat the complex constellation of symptoms with its associated comorbidities since not all children are cured by surgery (removal of the adenoids and tonsils). Given that dentists manage the teeth throughout the lifespan and have an important understanding of the anatomy and physiology involved with the airway from a dental perspective, it seems reasonable that better understanding and management from their field will give the opportunity to provide better integrated and optimized outcomes for children affected by OSA. With the emergence of therapies such as mandibular advancement devices and maxillary expansion, etc., dentists can be involved in providing care for OSA along with sleep medicine doctors. Furthermore, the evolving role of myofunctional therapy may also be indicated as adjunctive therapy in the management of children with OSA. The objective of this article is to discuss the important role of dentists and the collaborative approach between dentists, allied dental professionals such as myofunctional therapists, and sleep medicine specialists for identifying and managing children with OSA. Prevention and anticipatory guidance will also be addressed.

Neonates have distinctive anatomic and physiologic features that predispose them to obstructive sleep apnea (OSA). The overall prevalence of neonatal OSA is unknown, although an increase in prevalence has been reported in neonates with craniofacial malformations, neurological disorders, and airway malformations. If remained unrecognized and untreated, neonatal OSA can lead to impaired growth and development, cardiovascular morbidity, and can even be life threatening. Polysomnography and direct visualization of the airway are essential diagnostic modalities in neonatal OSA. Treatment of neonatal OSA is based on the severity of OSA and associated co-morbidities. This may include medical and surgical interventions individualized for the affected neonate. Based on this, it is expected that infants with OSA have more significant healthcare utilization.