Transitional care and clinical management of adolescents, young adults, and suspected new adult patients with congenital central hypoventilation syndrome

Slattery, Susan M.; Perez, Iris A.; Ceccherini, Isabella; Chen, Maida L.; Kurek, Kyle C.; Yap, Kai Lee; Keens, Thomas G.; Khaytin, Ilya; Ballard, Heather A; Sokol, Elizabeth; Mittal, Angeli; Rand, Casey M.; Weese‐Mayer, Debra E.

doi:10.1007/s10286-022-00908-8

Cited by 10 publications

(14 citation statements)

References 95 publications

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“…Currently no multigene panel exists for the diagnosis of CCHS. Most multigene panels are NGS‐based assays that are unable to detect PHOX2B PARMs (Slattery et al, 2022 ). The recommended stepwise testing with molecular methodologies to detect PHOX2B PARMs include Step 1 fragment analysis, and PHOX2B fragment analysis uses electrophoresis to detect all PARMs, NPARMs with nucleotide deletions and duplications that change the length of the coding sequence, and mosaicism (Jennings et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

“…If Step 1 is negative, then Step 2 Sanger sequencing can detect all PARMs and all NPARMs, but no low‐level mosaicism (Weese‐Mayer et al, 1993 ). If Steps 1 and 2 are negative but clinical suspicion of CCHS remains high, the Step 3 multiplex‐ligation dependent probe amplification testing is implemented to identify patients missing the whole PHOX2B gene with or without neighboring genes (Slattery et al, 2022 ). In this study, we used NGS combined with Sanger sequencing to detect the PHOX2B gene.…”

Section: Discussionmentioning

confidence: 99%

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Congenital central hypoventilation syndrome in Chinese population: Analysis of three new cases and review of the literature

Wang,

Chen

et al. 2023

Molec Gen & Gen Med

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BackgroundCongenital central hypoventilation syndrome (CCHS) is a rare autosomal dominant disease that is mainly caused by PHOX2B mutations. The purpose of this study is to analyze and summarize the clinical and genetic characteristics of CCHS patients in the Chinese population from our study and previous literature.MethodsThe potential pathogenic gene mutations of CCHS were identified and verified by next generation sequencing combined with Sanger sequencing, fluorescent probe PCR and capillary electrophoresis. The clinical characteristics and gene mutations of CCHS cases in Chinese population were summarized from our study and previous literature to explore the genotype–phenotype correlations.ResultsWe identified 48 CCHS cases including three new cases from our report in China. Overall, 77.1% of the patients had PHOX2B polyalanine repeat expansion mutations (PARMs), and the remaining 22.9% had 10 distinct PHOX2B non‐polyalanine repeat expansion mutations (NPARMs). Compared to those with PARMs, patients with NPARMs were more likely to have premature birth (54.5% vs. 2.8%, p < 0.001) and lower birth weight (33.3% vs. 3.2%, p = 0.030), with statistical significance. The patients with PARMs were more likely to have cardiovascular defects (64.9% vs. 27.3%, p = 0.063), cerebral hemorrhage (29.7% vs. 9.1%, p = 0.322) and seizures (37.8% vs. 9.1%, p = 0.151) than those with NPARMs, with no statistical significance.ConclusionsCCHS patients with PHOX2B NPARMs were more likely to have premature birth and low birth weight, while PHOX2B PARMs tended to be positively associated with the risk of cardiovascular defects, cerebral hemorrhage and seizures in Chinese population.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Congenital central hypoventilation syndrome in Chinese population: Analysis of three new cases and review of the literature

Wang,

Chen

et al. 2023

Molec Gen & Gen Med

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“…1,2,24 Since advances in CCHS diagnosis and management have led to prolonged survival, an increasing number of children are transitioning to adult care necessitating high-quality multidisciplinary programs for adults with CCHS. 4,25 Our study is limited by a single-center retrospective study design with a relatively small sample size. Patients in our study had relatively milder respiratory phenotypes requiring sleep-only AV which may not be representative of patients with more severe respiratory phenotypes.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Congenital Central Hypoventilation Syndrome: Diagnosis and Long-Term Ventilatory Outcomes

Fain

Westbrook

Kasi

2023

Clin Med Insights Pediatr

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Background: Congenital central hypoventilation syndrome (CCHS), a rare disease caused by variants in the paired-like homeobox 2B ( PHOX2B) gene, affects regulation of respiration necessitating lifelong assisted ventilation (AV). Most patients require full-time AV during infancy and some patients may sustain adequate spontaneous ventilation during wakefulness and change AV modalities at a later age. The aims of this study were to assess the changes in duration and modalities of AV, long-term respiratory outcomes, and to correlate them with PHOX2B genotypes. Methods: We conducted a retrospective study of patients with CCHS treated at our institution between January 1997 and May 2022. Results analyzed included: clinical presentation, PHOX2B genotype, modality and duration of AV at diagnosis and follow-up, survival, and transition to adult care. Results: We identified 30 patients with CCHS—8 with PHOX2B nonpolyalanine repeat mutations (NPARMs), 21 with polyalanine repeat mutations (PARMs), and 1 with unknown PHOX2B genotype. The median age at presentation was 0.25 months (IQR 0.1-0.7 months). At diagnosis of CCHS, 24 (80%) patients required continuous AV and 28 (93%) received AV via tracheostomy. Twenty-six patients required sleep-only AV at a median age of 9 months (IQR 6-14 months). Nine patients requiring sleep-only AV underwent tracheostomy decannulation at a median age of 11.2 years (IQR 5.9-15.7 years) and used noninvasive positive pressure ventilation or diaphragm pacing. There was insufficient evidence to conclude that patients with PARMs and NPARMs differed by age at presentation ( P = .39), tracheostomy ( P = .06), and transition to sleep-only AV ( P = .9). Six patients transitioned to adult care, 23 continued receiving pediatric care, and 1 patient died due to complications from Hirschsprung’s disease. Conclusion: Our study demonstrates prolonged survival and good long-term respiratory outcomes possibly related to the early diagnosis of CCHS, optimizing AV strategies, and multidisciplinary care. The increasing number of patients attaining adulthood highlights the necessity for multidisciplinary care for adults with CCHS.

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“…However, there is limited literature on optimal management strategies during pregnancy. 2 , 7 , 8 , 9 Therefore, comprehensive, multidisciplinary management may optimize care and improve maternal and fetal outcomes. 9 We report a case of a 31-year-old pregnant woman with CCHS who required bilevel positive airway pressure (BPAP) therapy during sleep and who delivered a healthy newborn by cesarean delivery.…”

Section: Introductionmentioning

confidence: 99%

Multidisciplinary approach to congenital central hypoventilation syndrome during pregnancy: case report

Akingbola,

Kasi,

Yamamura

et al. 2023

AJOG Global Reports

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Transitional care and clinical management of adolescents, young adults, and suspected new adult patients with congenital central hypoventilation syndrome

Cited by 10 publications

References 95 publications

Congenital central hypoventilation syndrome in Chinese population: Analysis of three new cases and review of the literature

Congenital central hypoventilation syndrome in Chinese population: Analysis of three new cases and review of the literature

Congenital Central Hypoventilation Syndrome: Diagnosis and Long-Term Ventilatory Outcomes

Multidisciplinary approach to congenital central hypoventilation syndrome during pregnancy: case report

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