Congenital central hypoventilation syndrome (CCHS)

Congenital central hypoventilation syndrome (CCHS) is a disorder characterized by an idiopathic failure of the automatic control of breathing. It is frequently associated with a broad spectrum of dysautonomic symptoms, suggesting the involvement of genes widely expressed in the autonomic nervous system. In particular, the HASH1/ASCL1-PHOX2A-PHOX2B developmental cascade was proposed as a candidate pathway. Recently, It has been showed that PHOX2B is the major CCHS locus, whose mutation accounts for 60% of cases.

Nervous system disease; Sleep disorder

PHOX2B [HSA:8929] [KO:K09330]
GDNF [HSA:2668] [KO:K05452]
RET [HSA:5979] [KO:K05126]
BDNF [HSA:627] [KO:K04355]
ASCL1 [HSA:429] [KO:K09067]
EDN3 [HSA:1908] [KO:K05227]

PMID:14566559

Sasaki A, Kanai M, Kijima K, Akaba K, Hashimoto M, Hasegawa H, Otaki S, Koizumi T, Kusuda S, Ogawa Y, Tuchiya K, Yamamoto W, Nakamura T, Hayasaka K

Molecular analysis of congenital central hypoventilation syndrome.

Hum Genet 114:22-6 (2003)

PMID:14532329

de Pontual L, Nepote V, Attie-Bitach T, Al Halabiah H, Trang H, Elghouzzi V, Levacher B, Benihoud K, Auge J, Faure C, Laudier B, Vekemans M, Munnich A, Perricaudet M, Guillemot F, Gaultier C, Lyonnet S, Simonneau M, Amiel J

Noradrenergic neuronal development is impaired by mutation of the proneural HASH-1 gene in congenital central hypoventilation syndrome (Ondine's curse).

Hum Mol Genet 12:3173-80 (2003)

PMID:15561428

Huang L, Guo H, Hellard DT, Katz DM

Glial cell line-derived neurotrophic factor (GDNF) is required for differentiation of pontine noradrenergic neurons and patterning of central respiratory output.

Neuroscience 130:95-105 (2005)