Congenital central hypoventilation syndrome neurocognition already reduced in preschool-aged children

Aaron J. Charnay, Jeanne E Antisdel*, Frank A Zelko, Casey M. Rand, Michele Le, Samantha C. Gordon, Sally F. Vitez, Jennifer W. Tse, Cindy D. Brogadir, Michael N. Nelson, Elizabeth M. Berry-Kravis, Debra E Weese-Mayer

*Corresponding author for this work

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

BACKGROUND: Congenital Central Hypoventilation Syndrome (CCHS) is a rare neurocristopathy characterized by severe hypoventilation and autonomic dysregulation, with typical presentation in the neonatal period, and deficient cognitive skills in school-aged patients. We hypothesized that younger (preschool) children with CCHS would also show neurocognitive delay and that CCHS-related physiologic factors would impact neurocognitive test results. METHODS: We studied developmental (Bayley) test results collected during routine clinical care in 31 children (mean age 25.0 ± 8.5 months; range, 6-40 months) with PHOX2B mutation-confirmed CCHS by comparing them with the normative reference mean from the Bayley standardization sample; we also examined associations between Bayley scores and CCHS disease-related factors. RESULTS: Preschool patients with CCHS fell significantly below the normative mean of 100 on Bayley indices of mental (mean, 83.35 ± 24.75) and motor (mean, 73.33 ± 20.48) development (P <.001 for both). Significantly lower Bayley mental and motor scores were associated with severe breath-holding spells, prolonged sinus pauses, and need for 24 h/d artificial ventilation. Lower Bayley motor scores were also associated with seizures. Bayley scores differed among children with the three most common polyalanine repeat expansion mutation genotypes (mental, P =.001; motor, P =.006), being essentially normal in children with the 20/25 genotype but significantly lower in the other genotype groups (P <.05). CONCLUSIONS: These results confirm neurodevelopmental impairment of CCHS preschoolers, with severity related to physiologic compromise and PHOX2B genotype. These findings suggest that adverse effects begin early in the disease process, supporting the need for neurodevelopmental monitoring and intervention from early infancy.

Original languageEnglish (US)
Pages (from-to)809-815
Number of pages7
JournalCHEST
Volume149
Issue number3
DOIs
StatePublished - Mar 1 2016

Fingerprint

Preschool Children
Genotype
Breath Holding
Hypoventilation
Mutation
Congenital central hypoventilation syndrome
Seizures

Keywords

  • Cognitive function
  • Genetics
  • Hypoventilation

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Charnay, Aaron J. ; Antisdel, Jeanne E ; Zelko, Frank A ; Rand, Casey M. ; Le, Michele ; Gordon, Samantha C. ; Vitez, Sally F. ; Tse, Jennifer W. ; Brogadir, Cindy D. ; Nelson, Michael N. ; Berry-Kravis, Elizabeth M. ; Weese-Mayer, Debra E. / Congenital central hypoventilation syndrome neurocognition already reduced in preschool-aged children. In: CHEST. 2016 ; Vol. 149, No. 3. pp. 809-815.
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abstract = "BACKGROUND: Congenital Central Hypoventilation Syndrome (CCHS) is a rare neurocristopathy characterized by severe hypoventilation and autonomic dysregulation, with typical presentation in the neonatal period, and deficient cognitive skills in school-aged patients. We hypothesized that younger (preschool) children with CCHS would also show neurocognitive delay and that CCHS-related physiologic factors would impact neurocognitive test results. METHODS: We studied developmental (Bayley) test results collected during routine clinical care in 31 children (mean age 25.0 ± 8.5 months; range, 6-40 months) with PHOX2B mutation-confirmed CCHS by comparing them with the normative reference mean from the Bayley standardization sample; we also examined associations between Bayley scores and CCHS disease-related factors. RESULTS: Preschool patients with CCHS fell significantly below the normative mean of 100 on Bayley indices of mental (mean, 83.35 ± 24.75) and motor (mean, 73.33 ± 20.48) development (P <.001 for both). Significantly lower Bayley mental and motor scores were associated with severe breath-holding spells, prolonged sinus pauses, and need for 24 h/d artificial ventilation. Lower Bayley motor scores were also associated with seizures. Bayley scores differed among children with the three most common polyalanine repeat expansion mutation genotypes (mental, P =.001; motor, P =.006), being essentially normal in children with the 20/25 genotype but significantly lower in the other genotype groups (P <.05). CONCLUSIONS: These results confirm neurodevelopmental impairment of CCHS preschoolers, with severity related to physiologic compromise and PHOX2B genotype. These findings suggest that adverse effects begin early in the disease process, supporting the need for neurodevelopmental monitoring and intervention from early infancy.",
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author = "Charnay, {Aaron J.} and Antisdel, {Jeanne E} and Zelko, {Frank A} and Rand, {Casey M.} and Michele Le and Gordon, {Samantha C.} and Vitez, {Sally F.} and Tse, {Jennifer W.} and Brogadir, {Cindy D.} and Nelson, {Michael N.} and Berry-Kravis, {Elizabeth M.} and Weese-Mayer, {Debra E}",
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Charnay, AJ, Antisdel, JE, Zelko, FA, Rand, CM, Le, M, Gordon, SC, Vitez, SF, Tse, JW, Brogadir, CD, Nelson, MN, Berry-Kravis, EM & Weese-Mayer, DE 2016, 'Congenital central hypoventilation syndrome neurocognition already reduced in preschool-aged children', CHEST, vol. 149, no. 3, pp. 809-815. https://doi.org/10.1378/chest.15-0402

Congenital central hypoventilation syndrome neurocognition already reduced in preschool-aged children. / Charnay, Aaron J.; Antisdel, Jeanne E; Zelko, Frank A; Rand, Casey M.; Le, Michele; Gordon, Samantha C.; Vitez, Sally F.; Tse, Jennifer W.; Brogadir, Cindy D.; Nelson, Michael N.; Berry-Kravis, Elizabeth M.; Weese-Mayer, Debra E.

In: CHEST, Vol. 149, No. 3, 01.03.2016, p. 809-815.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Congenital central hypoventilation syndrome neurocognition already reduced in preschool-aged children

AU - Charnay, Aaron J.

AU - Antisdel, Jeanne E

AU - Zelko, Frank A

AU - Rand, Casey M.

AU - Le, Michele

AU - Gordon, Samantha C.

AU - Vitez, Sally F.

AU - Tse, Jennifer W.

AU - Brogadir, Cindy D.

AU - Nelson, Michael N.

AU - Berry-Kravis, Elizabeth M.

AU - Weese-Mayer, Debra E

PY - 2016/3/1

Y1 - 2016/3/1

N2 - BACKGROUND: Congenital Central Hypoventilation Syndrome (CCHS) is a rare neurocristopathy characterized by severe hypoventilation and autonomic dysregulation, with typical presentation in the neonatal period, and deficient cognitive skills in school-aged patients. We hypothesized that younger (preschool) children with CCHS would also show neurocognitive delay and that CCHS-related physiologic factors would impact neurocognitive test results. METHODS: We studied developmental (Bayley) test results collected during routine clinical care in 31 children (mean age 25.0 ± 8.5 months; range, 6-40 months) with PHOX2B mutation-confirmed CCHS by comparing them with the normative reference mean from the Bayley standardization sample; we also examined associations between Bayley scores and CCHS disease-related factors. RESULTS: Preschool patients with CCHS fell significantly below the normative mean of 100 on Bayley indices of mental (mean, 83.35 ± 24.75) and motor (mean, 73.33 ± 20.48) development (P <.001 for both). Significantly lower Bayley mental and motor scores were associated with severe breath-holding spells, prolonged sinus pauses, and need for 24 h/d artificial ventilation. Lower Bayley motor scores were also associated with seizures. Bayley scores differed among children with the three most common polyalanine repeat expansion mutation genotypes (mental, P =.001; motor, P =.006), being essentially normal in children with the 20/25 genotype but significantly lower in the other genotype groups (P <.05). CONCLUSIONS: These results confirm neurodevelopmental impairment of CCHS preschoolers, with severity related to physiologic compromise and PHOX2B genotype. These findings suggest that adverse effects begin early in the disease process, supporting the need for neurodevelopmental monitoring and intervention from early infancy.

AB - BACKGROUND: Congenital Central Hypoventilation Syndrome (CCHS) is a rare neurocristopathy characterized by severe hypoventilation and autonomic dysregulation, with typical presentation in the neonatal period, and deficient cognitive skills in school-aged patients. We hypothesized that younger (preschool) children with CCHS would also show neurocognitive delay and that CCHS-related physiologic factors would impact neurocognitive test results. METHODS: We studied developmental (Bayley) test results collected during routine clinical care in 31 children (mean age 25.0 ± 8.5 months; range, 6-40 months) with PHOX2B mutation-confirmed CCHS by comparing them with the normative reference mean from the Bayley standardization sample; we also examined associations between Bayley scores and CCHS disease-related factors. RESULTS: Preschool patients with CCHS fell significantly below the normative mean of 100 on Bayley indices of mental (mean, 83.35 ± 24.75) and motor (mean, 73.33 ± 20.48) development (P <.001 for both). Significantly lower Bayley mental and motor scores were associated with severe breath-holding spells, prolonged sinus pauses, and need for 24 h/d artificial ventilation. Lower Bayley motor scores were also associated with seizures. Bayley scores differed among children with the three most common polyalanine repeat expansion mutation genotypes (mental, P =.001; motor, P =.006), being essentially normal in children with the 20/25 genotype but significantly lower in the other genotype groups (P <.05). CONCLUSIONS: These results confirm neurodevelopmental impairment of CCHS preschoolers, with severity related to physiologic compromise and PHOX2B genotype. These findings suggest that adverse effects begin early in the disease process, supporting the need for neurodevelopmental monitoring and intervention from early infancy.

KW - Cognitive function

KW - Genetics

KW - Hypoventilation

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