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Review
. 2023 Jun;33(3):217-230.
doi: 10.1007/s10286-022-00901-1. Epub 2022 Oct 27.

Neurocognition as a biomarker in the rare autonomic disorders of CCHS and ROHHAD

Frank A Zelko  1   2 , Remi Z Welbel  3 , Casey M Rand  3 , Tracey Stewart  3 , Allaa Fadl-Alla  3 , Ilya Khaytin  3 , Susan M Slattery  3 , Debra E Weese-Mayer  3
Affiliations
Review

Neurocognition as a biomarker in the rare autonomic disorders of CCHS and ROHHAD

Frank A Zelko et al. Clin Auton Res. 2023 Jun.

Abstract

Purpose: Congenital central hypoventilation syndrome (CCHS) and rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) are rare disorders of autonomic regulation with risk for disrupted neurocognitive development. Our aim is to summarize research on neurocognitive outcomes in these conditions, advance understanding of how to best support these individuals throughout development, and facilitate future research.

Methods: We conducted a narrative review of literature on neurocognitive outcomes in CCHS and ROHHAD, supplemented with previously unpublished data from patients with CCHS and ROHHAD at our Center for Autonomic Medicine in Pediatrics (CAMP).

Results: Individuals with CCHS and ROHHAD experience a wide range of neurocognitive functioning ranging from above average to below average, but are at particular risk for difficulties with working memory, processing speed, perceptual reasoning, and visuographic skills. An assessment framework emphasizing fluid cognition seems especially appropriate for these conditions. Owing to small cohorts and varied methods of data collection, it has been difficult to identify associations between disease factors (including CCHS PHOX2B genotypes) and cognitive outcomes. However, results suggest that early childhood is a period of particular vulnerability, perhaps due to the disruptive impact of recurrent intermittent hypoxic episodes on brain and cognitive development.

Conclusion: Neurocognitive monitoring is recommended as a component of routine clinical care in CCHS and ROHHAD as a marker of disease status and to ensure that educational support and disability accommodations are provided as early as possible. Collaborative efforts will be essential to obtain samples needed to enhance our understanding of neurocognitive outcomes in CCHS and ROHHAD.

Keywords: Autonomic (dys)regulation; Cognition; Congenital central hypoventilation syndrome (CCHS); PHOX2B; Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD).

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References

    1. Saiyed R, Rand C, Carroll MS, Weese-Mayer DE (2014) Hypoventilation syndromes of infancy, childhood, and adulthood: congenital central hypoventilation syndrome (CCHS), later-onset CCHS, and rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation. Sleep Med Clin 9:P425-439
    1. Weese-Mayer DE, Rand CM, Khaytin I, Slattery SM, Yap KL, Marazita ML, Berry-Kravis EM (2021) Congenital Central Hypoventilation Syndrome. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Mirzaa GM, Amemiya A (eds). GeneReviews((R)). Seattle (WA)
    1. Weese-Mayer DE, Berry-Kravis EM, Ceccherini I, Keens TG, Loghmanee DA, Trang H, Subcommittee ATSCCHS (2010) An official ATS clinical policy statement: congenital central hypoventilation syndrome: genetic basis, diagnosis, and management. Am J Respir Crit Care Med 181:626–644 - PubMed
    1. Weese-Mayer DE, Berry-Kravis EM, Zhou L, Maher BS, Silvestri JM, Curran ME, Marazita ML (2003) Idiopathic congenital central hypoventilation syndrome: analysis of genes pertinent to early autonomic nervous system embryologic development and identification of mutations in PHOX2b. Am J Med Genet A 123A:267–278 - PubMed
    1. Matera I, Bachetti T, Puppo F, Di Duca M, Morandi F, Casiraghi GM, Cilio MR, Hennekam R, Hofstra R, Schober JG, Ravazzolo R, Ottonello G, Ceccherini I (2004) PHOX2B mutations and polyalanine expansions correlate with the severity of the respiratory phenotype and associated symptoms in both congenital and late onset central hypoventilation syndrome. J Med Genet 41:373–380 - PubMed - PMC

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