BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare condition characterized by alveolar hypoventilation and autonomic nervous system (ANS) dysfunction requiring long-term ventilation. CCHS could constitute a risk factor of autism spectrum disorder (ASD) due to birth injury related to respiratory failure, which remains to be determined. ANS dysfunction has also been described in ASD and there are indications for altered contribution of ANS-central nervous system interaction in processing of social information; thus, CCHS could be a risk factor for ASD based on pathophysiological background also. Our study aimed to determine the prevalence of ASD among CCHS patients, identify risk factors, and explore the relationship between the ANS, evaluated by heart rate variability indices, and adaptative functioning.
RESULTS: Our retrospective study, based on the analysis of records of a French national center of patients with CCHS under 20 years of age, determined that the prevalence of ASD (diagnosed by a psychiatrist, following the criteria of DSM-4 or DSM-5) was 6/69 patients, 8.7% (95% confidence interval: 3.3-18.0%). In a case (CCHS with ASD, n = 6) - control (CCHS without ASD, n = 12) study with matching on sex, longer neonatal hospitalization stay and glycemic dysfunction were associated with ASD. Adaptative functioning was assessed using Vineland Adaptative behavioral scales (VABS) and heart rate variability indices (including daytime RMSSD as an index of parasympathetic modulation) were obtained from ECG Holter performed the same day. In 19 young subjects with CCHS who had both ECG Holter and VABS, significant positive correlations were observed between RMSSD and three of four sub-domains of the VABS (communication: R = 0.50, p = 0.028; daily living skills: R = 0.60, p = 0.006; socialization: R = 0.52, p = 0.021).
CONCLUSIONS: Our study suggests a high prevalence of ASD in patients with CCHS. Glycemic dysfunction and longer initial hospitalization stays were associated with ASD development. A defect in parasympathetic modulation was associated with worse adaptative functioning.

UNASSIGNED: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) details assessment and management of the child with overweight or obesity. The term \"child\" is defined as the child between 2 and 12 years of age. Because children are in a continual state of development during this age range, we will specify when our discussion applies to subsets within this age range. For the purposes of this CPS, we will use the following definitions: overweight in the child is a body mass index (BMI) ≥ 85th and <95th percentile, obesity in the child is a BMI ≥95th percentile, and severe obesity is a BMI ≥120% of the 95th percentile.
UNASSIGNED: The information and clinical guidance in this OMA Clinical Practice Statement are based on scientific evidence, supported by medical literature, and derived from the clinical perspectives of the authors.
UNASSIGNED: This OMA Clinical Practice Statement provides an overview of prevalence of disease in this population, reviews precocious puberty in the child with obesity, discusses the current and evolving landscape of the use of anti-obesity medications in children in this age range, discusses the child with obesity and special health care needs, and reviews hypothalamic obesity in the child.
UNASSIGNED: This OMA Clinical Practice Statement on the child with obesity is an evidence based review of the literature and an overview of current recommendations. This CPS is intended to provide a roadmap to the improvement of the health of children with obesity, especially those with metabolic, physiological, psychological complications and/or special healthcare needs. This CPS addresses treatment recommendations and is designed to help the clinician with clinical decision making.

BACKGROUND: Overlap syndrome (OS), the coexistence of chronic obstructive pulmonary disease and obstructive sleep apnea, is frequently characterized by the presence of daytime hypercapnia (pCO2 ≥ 45 mmHg). The aim of this study was to investigate potential differences in anthropometric, sleep and respiratory characteristics between hypercapnic and normocapnic patients with OS.
METHODS: Consecutive patients who underwent polysomnography, pulmonary function testing and arterial blood gases and had been diagnosed with OS were enrolled in the study.
RESULTS: According to pCO2 levels in wakefulness, the patients were divided into group A, consisting of OS patients without hypercapnia (n = 108) or group B, consisting of OS patients with hypercapnia (n = 55). The majority of included patients in both groups were males (n = 92 in group A vs. n = 50 in group B). Group B had increased BMI (p = 0.001), neck (p = 0.017) and waist circumference (p = 0.013), higher scores in Epworth sleepiness scale (ESS) (p = 0.008), increased sleep efficiency (p = 0.033), oxygen desaturation index (p = 0.004) and time with oxyhemoglobin saturation <90% (p = 0.006) than group A. Also, Group B had decreased average and minimum oxyhemoglobin saturation during sleep (p < 0.001). Hypercapnic patients had lower FEV1% (p = 0.003), FVC% (p = 0.004), pO2 and pCO2 (p < 0.001 for both) values compared with normocapnic patients. In binary regression analysis, which assessed various predictors on the likelihood of having hypercapnia, it was found that BMI (OR: 1.313, 95% CI: 1.048-1.646, p = 0.018) and FVC (OR: 0.913, 95% CI: 0.845-0.986, p = 0.020) were the major determinants of hypercapnia in OS patients.
CONCLUSIONS: Hypercapnic OS patients were more obese and sleepy and presented worse respiratory function in wakefulness and sleep hypoxia characteristics compared with normocapnic OS patients.

OBJECTIVE: To report the association of zinc finger and SCAN domain containing 1 antibodies (ZSCAN1-abs) with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome in patients without tumor.
METHODS: Patients with symptoms compatible with ROHHAD syndrome but without an associated tumor were selected from our database. Serum and CSF samples were examined for the presence of ZSCAN1-abs by an in-house cell-based assay. In addition, samples from 149 patients with several inflammatory and noninflammatory disorders and 50 healthy participants served as controls.
RESULTS: Thirteen patients with ROHHAD syndrome were identified. Of these, we had paired serum/CSF samples from 6 patients and only serum from the other 7. Five of 6 patients (83.3%) with paired serum/CSF (4 children, 1 adult) had ZSCAN-abs only in CSF and 1 had antibodies in serum and CSF. ZSCAN1-abs were not detected in the remaining 7 patients with ROHHAD with only serum available or in any of the 199 control samples.
CONCLUSIONS: Patients with ROHHAD syndrome should be investigated for the presence of ZSCAN1-abs in CSF. The antibodies do not necessarily predict the presence of a tumor. The detection of ZSCAN1-abs in an adult patient suggests that this condition also occurs beyond the pediatric age.

Mutations in the transcription factors encoded by PHOX2B or LBX1 correlate with congenital central hypoventilation disorders. These conditions are typically characterized by pronounced hypoventilation, central apnea, and diminished chemoreflexes, particularly to abnormally high levels of arterial PCO2. The dysfunctional neurons causing these respiratory disorders are largely unknown. Here, we show that distinct, and previously undescribed, sets of medullary neurons coexpressing both transcription factors (dB2 neurons) account for specific respiratory functions and phenotypes seen in congenital hypoventilation. By combining intersectional chemogenetics, intersectional labeling, lineage tracing, and conditional mutagenesis, we uncovered subgroups of dB2 neurons with key functions in (i) respiratory tidal volumes, (ii) the hypercarbic reflex, (iii) neonatal respiratory stability, and (iv) neonatal survival. These data provide functional evidence for the critical role of distinct medullary dB2 neurons in neonatal respiratory physiology. In summary, our work identifies distinct subgroups of dB2 neurons regulating breathing homeostasis, dysfunction of which causes respiratory phenotypes associated with congenital hypoventilation.

The timely introduction of non-invasive ventilation (NIV) is extremely relevant in the multidisciplinary management of patients affected by amyotrophic lateral sclerosis (ALS) and is based on the proper identification of red flags for early diaphragmatic exhaustion. Polygraphic sleep recording may provide insightful information on the ongoing respiratory impairment; in particular, atypical breathing patterns need to be recognized, as the application of current guidelines for sleep-related hypoxemia or sleep apnea may be insufficient for detecting early signs of diaphragmatic fatigue. We report the case of a 51-year-old man affected by ALS who was asymptomatic for breathing impairment, but whose nocturnal polysomnographic recording, despite not significant for obstructive sleep apnea nor for conventional hypoventilatory patterns, strongly suggested initial respiratory failure, as lately confirmed by the pulmonary follow-up. We discuss the advantages of including sleep recording in the clinical work-up of patients affected by ALS.

PHOX2B is a transcription factor essential for the development of different classes of neurons in the central and peripheral nervous system. Heterozygous mutations in the PHOX2B coding region are responsible for the occurrence of Congenital Central Hypoventilation Syndrome (CCHS), a rare neurological disorder characterised by inadequate chemosensitivity and life-threatening sleep-related hypoventilation. Animal studies suggest that chemoreflex defects are caused in part by the improper development or function of PHOX2B expressing neurons in the retrotrapezoid nucleus (RTN), a central hub for CO2 chemosensitivity. Although the function of PHOX2B in rodents during development is well established, its role in the adult respiratory network remains unknown. In this study, we investigated whether reduction in PHOX2B expression in chemosensitive neuromedin-B (NMB) expressing neurons in the RTN altered respiratory function. Four weeks following local RTN injection of a lentiviral vector expressing the short hairpin RNA (shRNA) targeting Phox2b mRNA, a reduction of PHOX2B expression was observed in Nmb neurons compared to both naive rats and rats injected with the non-target shRNA. PHOX2B knockdown did not affect breathing in room air or under hypoxia, but ventilation was significantly impaired during hypercapnia. PHOX2B knockdown did not alter Nmb expression but it was associated with reduced expression of both Task2 and Gpr4, two CO2/pH sensors in the RTN. We conclude that PHOX2B in the adult brain has an important role in CO2 chemoreception and reduced PHOX2B expression in CCHS beyond the developmental period may contribute to the impaired central chemoreflex function.

An emerging body of literature describes the prevalence and consequences of hypercapnic respiratory failure. While device qualifications, documentation practices, and previously performed clinical studies often encourage conceptualizing patients as having a single \"cause\" of hypercapnia, many patients encountered in practice have several contributing conditions. Physiologic and epidemiologic data suggest that sleep-disordered breathing-particularly obstructive sleep apnea (OSA)-often contributes to the development of hypercapnia. In this review, the authors summarize the frequency of contributing conditions to hypercapnic respiratory failure among patients identified in critical care, emergency, and inpatient settings with an aim toward understanding the contribution of OSA to the development of hypercapnia.

Obstructive sleep apnea (OSA) is very prevalent in sarcoidosis patients. Sarcoidosis of the upper respiratory tract may affect upper airway patency and increase the risk of OSA. Weight gain due to steroid use, upper airway myopathy due to steroids and sarcoidosis itself, and interstitial lung disease with decreased upper airway patency are other reasons for the higher OSA prevalence seen in sarcoidosis. Several clinical manifestations such as fatigue, hypersomnolence, cognitive deficits, and pulmonary hypertension are common to both OSA and sarcoidosis. Therefore, early screening and treatment for OSA can improve symptoms and overall patient quality of life.

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