Vagal and sympathetic heart rate and blood pressure control in adult onset PHOX2B mutation-confirmed congenital central hypoventilation syndrome

被引:24
作者
Diedrich, Andre [1 ]
Malow, Beth A.
Antic, Nick A.
Sato, Kyoko
McEvoy, R. Doug
Mathias, Christopher J.
Robertson, David
Berry-Kravis, Elizabeth M.
Weese-Mayer, Debra E.
机构
[1] Vanderbilt Univ, Sch Med, Auton Dysfunct Ctr, Dept Med,Div Clin Pharmacol, Nashville, TN 37212 USA
[2] Vanderbilt Univ, Sch Med, Dept Neurol, Nashville, TN 37212 USA
[3] Vanderbilt Univ, Sch Med, Vanderbilt Sleep Disorders Ctr, Nashville, TN 37212 USA
[4] Repatriat Gen Hosp, Adelaide Inst Sleep Hlth, Daw Pk, SA, Australia
[5] Natl Hosp Neurol & Neurosurg, Auton Unit, London WC1N 3BG, England
[6] St Marys Hosp, Imperial Coll London, Fac Med, Neurovasc Med Unit, London, England
[7] Vanderbilt Univ, Sch Med, Ctr Mol Neurosci, Nashville, TN 37212 USA
[8] Rush Univ, Med Ctr, Dept Pediat, Chicago, IL 60612 USA
[9] Rush Univ, Med Ctr, Dept Neurol & Biochem, Chicago, IL 60612 USA
关键词
congenital central hypoventilation syndrome; PHOX2B; autonomic nervous system; muscle; sympathetic activity; baroreflex; heart rate variability; blood pressure variability;
D O I
10.1007/s10286-007-0421-4
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background Children with Congenital Central Hypoventilation Syndrome (CCHS) typically present as newborns with alveolar hypoventilation. With the advent of genetic testing, parents of affected children and other unrelated adults, all heterozygous for the disease-defining PHOX2B polyalanine expansion mutation with the 20/25 genotype, are being identified in adulthood. Though children with PHOX2B mutation-confirmed CCHS demonstrate ANS dysregulation, including altered heart rate and blood pressure control, it is unknown if adults with CCHS have similarly affected autonomic function in blood pressure control. Methods and Results An autonomic profile of blood pressure control has been studied with recording of muscle sympathetic activity and spectral analysis of heart rate and blood pressure variability of one adult patient with alveolar hypoventilation and the 20/25 PHOX2B genotype. All parameters of heart rate variability were reduced. Cardiac baroreflex sensitivity was decreased. Sympathetic responses to Valsalva maneuver, hypoxemia, isometric exercise and cold pressor were blunted. Conclusion In summary, we found a reduced cardiac baroreflex and a blunted sympathetic mediated response in the individual with adult-onset CCHS, possibly due to dysfunction in the afferent pathway. Our results confirm that PHOX2B affects the development of the autonomic nervous system, possibly causing absence of normal maturation of carotid body and visceral sensory ganglia and leading to autonomic dysfunction in adult-onset CCHS.
引用
收藏
页码:177 / 185
页数:9
相关论文
共 29 条
  • [1] Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome
    Amiel, J
    Laudier, B
    Attié-Bitach, T
    Trang, H
    de Pontual, L
    Gener, B
    Trochet, D
    Etchevers, H
    Ray, P
    Simonneau, M
    Vekemans, M
    Munnich, A
    Gaultier, C
    Lyonnet, S
    [J]. NATURE GENETICS, 2003, 33 (04) : 459 - 461
  • [2] Primary alveolar hypoventilation and response to the respiratory stimulant almitrine
    Antic, N
    McEvoy, RD
    [J]. INTERNAL MEDICINE JOURNAL, 2002, 32 (12) : 622 - U2
  • [3] PHOX2B mutation-confirmed congenital central hypoventilation syndrome -: Presentation in adulthood
    Antic, Nick A.
    Mallow, Beth A.
    Lange, Neale
    McEvoy, R. Doug
    Olson, Amy L.
    Turkington, Peter
    Windisch, Wolfram
    Samuels, Martin
    Stevens, Cathy A.
    Berry-Kravis, Elizabeth M.
    Weese-Mayer, Debra E.
    [J]. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2006, 174 (08) : 923 - 927
  • [4] Congenital central hypoventilation syndrome -: PHOX2B mutations and phenotype
    Berry-Kravis, Elizabeth M.
    Zhou, Lili
    Rand, Casey M.
    Weese-Mayer, Debra E.
    [J]. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2006, 174 (10) : 1139 - 1144
  • [5] Camm AJ, 1996, EUR HEART J, V17, P354
  • [6] GENERAL CHARACTERISTICS OF SYMPATHETIC ACTIVITY IN HUMAN MUSCLE NERVES
    DELIUS, W
    HAGBARTH, KE
    WALLIN, BG
    HONGELL, A
    [J]. ACTA PHYSIOLOGICA SCANDINAVICA, 1972, 84 (01): : 65 - &
  • [7] Sleep-disordered breathing in newborn mice heterozygous for the transcription factor Phox2b
    Durand, E
    Dauger, S
    Pattyn, A
    Gaultier, C
    Goridis, C
    Gallego, J
    [J]. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2005, 172 (02) : 238 - 243
  • [8] Aberrant neural responses to cold pressor challenges in congenital central hypoventilation syndrome
    Macey, PM
    Macey, KE
    Woo, MA
    Keens, TG
    Harper, RM
    [J]. PEDIATRIC RESEARCH, 2005, 57 (04) : 500 - 509
  • [9] Chronic obstructive pulmonary disease
    Madison, JM
    Irwin, RS
    [J]. LANCET, 1998, 352 (9126) : 467 - 473
  • [10] 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
    Matera, I
    Bachetti, T
    Puppo, F
    Di Duca, M
    Morandi, F
    Casiraghi, GM
    Cilio, MR
    Hennekam, R
    Hofstra, R
    Schöber, JG
    Ravazzolo, R
    Ottonello, G
    Ceccherini, I
    [J]. JOURNAL OF MEDICAL GENETICS, 2004, 41 (05) : 373 - 380