Variable phenotypes in congenital central hypoventilation syndrome with
            <i>PHOX2B</i>
            nonpolyalanine repeat mutations

Kasi, Ajay S; Li, Hong; Jurgensen, Taryn J; Guglani, Lokesh; Keens, Thomas G.; Perez, Iris A.

doi:10.5664/jcsm.9370

Cited by 10 publications

(18 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both intrafamilial and interfamilial variable expression and incomplete penetrance among individuals with PHOX2B variants have been reported, indicating other genetic modifiers and/or environmental factors are contributory to the broad spectrum of clinical manifestations. 7 , 19 , 20 …”

Section: Geneticsmentioning

confidence: 99%

“…Therefore, close monitoring of each patient and regular surveillance studies are essential to identify early manifestations and to formulate an individualized plan of care. 7 These evaluations include comprehensive respiratory assessments during sleep and wakefulness to assess ventilatory needs, polysomnography with titration of ventilator settings to maintain oxygen saturation (SpO 2 ) ≥95% and end-tidal carbon dioxide (ETCO 2 ) between 35–40 mm Hg, echocardiogram to assess for pulmonary hypertension, ambulatory cardiac monitoring to detect cardiac arrhythmias, imaging and urine studies for NCT, ophthalmologic and neurocognitive testing, and airway endoscopy for patients with a tracheostomy ( Table 1 ). 1 , 3 Coordinating these tests during in-hospital evaluations may be beneficial in formulating a comprehensive management plan.…”

Section: Clinical Featuresmentioning

confidence: 99%

“…In addition, the clinical features of CCHS can evolve over time. 7 Therefore, a coordinated comprehensive multidisciplinary approach to care is vital to ensure the best possible outcomes throughout the lifespan. Coordination of care among disciplines can be complicated and challenging for the patient and the family ( Figure 1 ).…”

Section: Clinical Featuresmentioning

confidence: 99%

“…Later in infancy or during early childhood, their respiratory pattern may evolve to sustain adequate ventilation during wakefulness likely due to maturation of the respiratory system. 7 , 12 To assess the ventilatory requirement of the child and ability to breathe spontaneously during wakefulness, ventilator sprint weaning is performed by disconnecting AV for a brief duration (generally 30–60 minutes) under close medical supervision with pulse oximetry and ETCO 2 monitoring. If there is hypoxemia or hypoventilation, sprint weaning is discontinued.…”

Section: Clinical Featuresmentioning

confidence: 99%

“…The identification of the PHOX2B gene as the disease-causing link to CCHS has led to earlier confirmation of the diagnosis, institution of AV, and evaluation for associated conditions. 1 , 7 With advances in management strategies, increased awareness of CCHS, and multidisciplinary care, children with CCHS are surviving into adulthood with a good quality of life. 8 , 9 In this review, we will discuss the clinical features of CCHS and optimizing management using a multidisciplinary care approach.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Congenital Central Hypoventilation Syndrome: Optimizing Care with a Multidisciplinary Approach

Kasi¹,

Li²,

Harford³

et al. 2022

JMDH

Self Cite

View full text Add to dashboard Cite

Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder affecting respiratory control and autonomic nervous system function caused by variants in the paired-like homeobox 2B ( PHOX2B ) gene. Although most patients are diagnosed in the newborn period, an increasing number of patients are presenting later in childhood, adolescence, and adulthood. Despite hypoxemia and hypercapnia, patients do not manifest clinical features of respiratory distress during sleep and wakefulness. CCHS is a lifelong disorder. Patients require assisted ventilation throughout their life delivered by positive pressure ventilation via tracheostomy, noninvasive positive pressure ventilation, and/or diaphragm pacing. At different ages, patients may prefer to change their modality of assisted ventilation. This requires an individualized and coordinated multidisciplinary approach. Additional clinical features of CCHS that may present at different ages and require periodic evaluations or interventions include Hirschsprung’s disease, gastrointestinal dysmotility, neural crest tumors, cardiac arrhythmias, and neurodevelopmental delays. Despite an established PHOX2B genotype and phenotype correlation, patients have variable and heterogeneous clinical manifestations requiring the formulation of an individualized plan of care based on collaboration between the pulmonologist, otolaryngologist, cardiologist, anesthesiologist, gastroenterologist, sleep medicine physician, geneticist, surgeon, oncologist, and respiratory therapist. A comprehensive multidisciplinary approach may optimize care and improve patient outcomes. With advances in CCHS management strategies, there is prolongation of survival necessitating high-quality multidisciplinary care for adults with CCHS.

show abstract

Section: Geneticsmentioning

confidence: 99%

Section: Clinical Featuresmentioning

confidence: 99%

Section: Clinical Featuresmentioning

confidence: 99%

Section: Clinical Featuresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Congenital Central Hypoventilation Syndrome: Optimizing Care with a Multidisciplinary Approach

Kasi¹,

Li²,

Harford³

et al. 2022

JMDH

Self Cite

View full text Add to dashboard Cite

show abstract

Impaired ventilation during 6‐min walk test in congenital central hypoventilation syndrome

Ghosh

Guglani

Westbrook

et al. 2022

Pediatric Pulmonology

Self Cite

View full text Add to dashboard Cite

Background Patients with congenital central hypoventilation syndrome (CCHS) can develop hypoxemia and hypercapnia during exercise. However, there is limited literature on cardiorespiratory responses during submaximal exercise and their correlation with paired‐like homeobox 2B (PHOX2B) genotype. Objectives To assess oxygen saturation (SpO2), end‐tidal carbon dioxide (ETCO2), heart rate (HR), and 6‐min walk distance (6MWD) during a 6‐min walk test (6MWT) in CCHS subjects and to correlate them with PHOX2B genotypes and assisted ventilation (AV) via tracheostomy. Methods In this cross‐sectional study, subjects with CCHS performed 6MWT with continuous pulse oximetry, HR, and capnography recorded before and during the 6MWT. Medical records were reviewed for PHOX2B genotype and phenotype data. Patients were categorized based on PHOX2B genotype and AV via tracheostomy. Results Fifteen subjects aged 10.5 (interquartile range 7.9−16.2) years completed the 6MWT. Nine subjects used AV via tracheostomy. Seven (47%) subjects developed hypoxemia (SpO2 ≤ 90%, n = 7) and hypoventilation (ETCO2 ≥ 50 mmHg, n = 3) during the 6MWT. There was a significant decline from baseline SpO2, increase from baseline ETCO2, and increase in HR during the 6MWT (all p < 0.05). Subjects had decreased median percent predicted 6MWD (59.7% [50.6%−62.5%]). Nadir SpO2 (p = 0.029) and peak ETCO2 (p = 0.046) differed significantly between PHOX2B genotype groups but 6MWD did not (p = 0.8). Conclusion Despite normal oxygenation and ventilation at rest and during sleep on AV, patients with CCHS can develop hypoxemia and hypercapnia during submaximal exercise. Our study highlights the importance of assessing ventilatory responses during submaximal exercise in patients with CCHS regardless of their PHOX2B genotype.

show abstract

Tracheostomy and inpatient outcomes among children with congenital central hypoventilation syndrome: A kids' inpatient database study

Tsou,

Tapia

2024

Pediatric Pulmonology

View full text Add to dashboard Cite

Study ObjectivesCongenital central hypoventilation syndrome (CCHS) is a rare disease predisposing children to respiratory failure due to abnormal ventilatory drive. Variability in hypoventilation and respiratory support need have been reported. We aim to identify clinical variables associated with incident tracheostomy and common etiologies of hospitalization among children with CCHS.MethodsHospital discharge records were obtained for children (<21 years) with CCHS hospitalized between 2006 and 2019 from the Kid's Inpatient Database. Primary diagnostic categories for hospitalizations with CCHS were summarized. Multivariable logistic regression models were used to explore risk factors associated with incident tracheostomy.ResultsAmong 2404 hospitalizations with CCHS, 133 (5.5%) had incident tracheostomy, 1230 (51.2%) had established tracheostomy, and 1041 (43.3%) had no tracheostomy. Compared with children without tracheostomy, those with incident tracheostomy were younger, had a history of prematurity, congenital heart disease, laryngeal, glottic, and subglottic stenosis (LGSS), congenital airway anomalies, neuromuscular weakness, gastroesophageal reflux disease. Children without tracheostomy had higher mortality than those with tracheostomy status (2.19% vs. 0.66%). Multivariable‐adjusted analyses showed that incident tracheostomy was associated with infancy (0–1 years), neuromuscular weakness, and congenital heart disease. Most common diagnostic categories include (1) diseases of the respiratory system (30.23%), (2) injury and poisoning (9.35%), and (3) diseases of the nervous system and sense organs (6.71%).ConclusionsChildren with CCHS who received incident tracheostomy are more likely to be younger and with LGSS, neuromuscular weakness and congenital heart disease. Clinicians should be aware of these risk factors representing more severe CCHS with earlier manifestation needing tracheostomy. Higher mortality among nontracheostomy group highlights the need for considering tracheostomy in caring for children with CCHS.

show abstract

Variable phenotypes in congenital central hypoventilation syndrome with PHOX2B nonpolyalanine repeat mutations

Cited by 10 publications

References 29 publications

Congenital Central Hypoventilation Syndrome: Optimizing Care with a Multidisciplinary Approach

Congenital Central Hypoventilation Syndrome: Optimizing Care with a Multidisciplinary Approach

Impaired ventilation during 6‐min walk test in congenital central hypoventilation syndrome

Tracheostomy and inpatient outcomes among children with congenital central hypoventilation syndrome: A kids' inpatient database study

Contact Info

Product

Resources

About