Ondine's curse
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2008-07-02T16:04:55Z
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{{Infobox_Disease |
Name = Ondine's curse |
Image = John William Waterhouse - Undine.JPG |
Caption = ''Ondine'', by [[John William Waterhouse]] (1872) |
DiseasesDB = 32976 |
ICD10 = {{ICD10|G|47|3|g|40}} |
ICD9 = {{ICD9|348.8}} |
ICDO = |
OMIM = 209880 |
MedlinePlus = 000078 |
eMedicineSubj = ped |
eMedicineTopic = 1645 |
MeshID = D020182 |
}}
'''Ondine's Curse''', also called '''congenital central hypoventilation syndrome''' ('''CCHS''') or '''primary alveolar hypoventilation''', is a respiratory disorder that is fatal if untreated. Persons afflicted with Ondine's curse classically suffer from [[respiratory arrest]] during sleep.
This very rare and serious form of central [[sleep apnea]] involves an inborn failure of [[autonomic nervous system|autonomic control]] of breathing. About 1 in 200,000 live born children have the condition. In 2006, there were only about 200 known cases worldwide. In all cases, episodes of [[apnea]] occur in sleep, but in a few patients, at the most severe end of the spectrum, apnea also occurs while awake.
==Symptoms==
Ondine's curse is associated with respiratory arrests during sleep and, with incomplete [[penetrance]], [[neuroblastoma]] (tumors of the [[sympathetic ganglia]]), [[Hirschprung disease]] (partial agenesis of the [[enteric nervous system]]), [[dysphagia]] (difficulty swallowing), anomalies of the pupilla, etc.
==Causes==
Ondine's curse is exhibited typically as a [[congenital]] disorder, but in rare circumstances, can also result from severe brain or spinal trauma (such as after an [[automobile accident]], [[stroke]], or as a complication of [[neurosurgery]]).
Medical investigation of patients with this syndrome has led to a deeper understanding of how the body and brain regulate breathing on a molecular level. [[PHOX2B]] can be associated with this condition.<ref>{{cite journal |author=Gaultier C, Amiel J, Dauger S, ''et al'' |title=Genetics and early disturbances of breathing control |journal=Pediatr. Res. |volume=55 |issue=5 |pages=729–33 |year=2004 |pmid=14739359 |doi=10.1203/01.PDR.0000115677.78759.C5}}</ref><ref>{{cite journal |author=Gaultier C, Trang H, Dauger S, Gallego J |title=Pediatric disorders with autonomic dysfunction: what role for PHOX2B? |journal=Pediatr. Res. |volume=58 |issue=1 |pages=1–6 |year=2005 |pmid=15901893 |doi=10.1203/01.PDR.0000166755.29277.C4}}</ref><ref>{{cite journal |author=Todd ES, Weinberg SM, Berry-Kravis EM, ''et al'' |title=Facial phenotype in children and young adults with PHOX2B-determined congenital central hypoventilation syndrome: quantitative pattern of dysmorphology |journal=Pediatr. Res. |volume=59 |issue=1 |pages=39–45 |year=2006 |pmid=16327002 |doi=10.1203/01.pdr.0000191814.73340.1d}}</ref><ref>"[http://news.bbc.co.uk/1/hi/health/2996791.stm Gene secret of 'mythical curse']" at [[BBC News]], [[5 May]] [[2003]] (The article misspells [[PHOX2B]] as "Thox2b".)</ref> This [[homeobox gene]] is important for the normal development of the [[autonomic nervous system]].
The disease used to be classified as a "neurocristopathy",<ref name="pmid7991820">{{cite journal |author=Kincaid PK, Dietrich RB, Pais MJ |title=Pediatric case of the day. Neurocristopathy (Ondine-Hirschsprung syndrome) |journal=Radiographics : a review publication of the Radiological Society of North America, Inc |volume=14 |issue=5 |pages=1139–43 |year=1994 |pmid=7991820 |doi=}}</ref><ref name="pmid3508086">{{cite journal |author=Poceta JS, Strandjord TP, Badura RJ, Milstein JM |title=Ondine curse and neurocristopathy |journal=Pediatr. Neurol. |volume=3 |issue=6 |pages=370–2 |year=1987 |pmid=3508086 |doi=10.1016/0887-8994(87)90011-7}}</ref> or disease of the [[neural crest]] because part of the [[autonomic nervous system]] (such as sympathetic ganglia) derives from the neural crest. However, this denomination should be dropped because essential neurons of the autonomic nervous system, including those that underlie the defining symptom of the disease (respiratory arrests), are derived from the [[neural tube]] (the [[medulla]]), not from the neural crest.
==Diagnosis==
Children with Congenital Central Hypoventilaion Syndrome develop life-threatening episodes of apnea with [[cyanosis]], usually in the first months of life. Medical evaluation excludes lesions of the brain, heart, and lungs but demonstrate impaired responses to build-up of carbon dioxide ([[hypercapnia]]) and decreases of oxygen in the circulation ([[Hypoxia (medical)|hypoxia]]), the two strongest stimuli to increase breathing rate.
[[Polysomnography]] shows that hypoventilation is most marked during [[slow-wave sleep]]. In the most severe cases, [[hypoventilation]] is present during other nonrapid eye movement sleep stages and even wakefulness. A subset of CCHS patients are at very high risk for developing malignant neural crest derived [[tumors]], such as [[neuroblastoma]].
The sequence of ''[[PHOX2B]]'' reveals mutations in 91% of the cases.<ref>{{cite journal |author=Trang H, Dehan M, Beaufils F, Zaccaria I, Amiel J, Gaultier C |title=The French Congenital Central Hypoventilation Syndrome Registry: general data, phenotype, and genotype |journal=Chest |volume=127 |issue=1 |pages=72–9 |year=2005 |pmid=15653965 |doi=10.1378/chest.127.1.72}}</ref>
As in many disorders that are very rare, an infant with this unusual form of [[sleep apnea]] suffers from the probability that their physician has most likely never seen another case and will not recognize the diagnosis. In some locations, such as France, optimal management of patients, once identified, has been aided by the creation of a national registry and the formation of a network of centers.
==Treatment and prognosis==
Patients generally require [[tracheotomy|tracheotomies]] and lifetime mechanical ventilation on a ventilator in order to survive. However, it is now been shown that [[Biphasic Cuirass Ventilation]] can effectively be used without the need of a tracheotomy.
Most people with congenital Ondine's curse do not survive infancy, unless they receive ventilatory assistance during sleep. An alternative to a mechanical ventilator is [[Phrenic Nerve Pacing]]/diaphragm pacing.<ref>{{cite journal |author=Takeda S, Fujii Y, Kawahara H, Nakahara K, Matsuda H |title=Central alveolar hypoventilation syndrome (Ondine's curse) with gastroesophageal reflux |journal=Chest |volume=110 |issue=3 |pages=850–2 |year=1996 |pmid=8797441 |doi=10.1378/chest.110.3.850}}</ref>
Although rare, cases of long-term untreated CCHS have been reported.<ref>{{cite journal | author = Windisch W, Hennings E, Storre J, Matthys H, Sorichter S | title = Long-term survival of a patient with congenital central hypoventilation syndrome despite the lack of continuous ventilatory support | journal = Respiration | volume = 71 | issue = 2 | pages = 195–8 | year = 2004| pmid = 15031579 | doi = 10.1159/000076685}}</ref>
==History and etymology==
It was first described in [[1962]] by Severinghaus and Mitchell in three patients following surgery to the upper cervical [[spinal cord]] and [[brainstem]].<ref>Severinghaus JW, Mitchell RA. Ondine's curse - failure of respiratory center automaticity while awake. ''Clin Res'' 1962;10:122.</ref>
Its name is a reference to the [[Mythology|myth]] of [[Ondine (mythology)|Ondine]],<ref>{{cite journal |author=Nannapaneni R, Behari S, Todd NV, Mendelow AD |title=Retracing "Ondine's curse" |journal=Neurosurgery |volume=57 |issue=2 |pages=354–63; discussion 354–63 |year=2005 |pmid=16094167 |doi=}}</ref> a water nymph who had an unfaithful mortal lover. He swore to her that his "every waking breath would be a testimony of [his] love", and upon witnessing his adultery, she cursed that if he should fall asleep, he would forget to breathe. Eventually, he fell asleep from sheer exhaustion, and his breathing stopped.
==Cultural references==
* Ondine's curse was mentioned in the 1987 film ''[[Black Widow (1987 film)|Black Widow]]'' starring [[Debra Winger]], [[Theresa Russell]], [[Terry O'Quinn]] and [[D. W. Moffett]]. Ondine's Curse was given as a reason for the death of a mafia connected man who suddenly died in his sleep for no reason.
* Ondine's curse was also mentioned in the book [[It's Kind of A Funny Story]] ([[Ned Vizzini]]). The main character describes the phenomenon after having read it in ''DSM'' (the [[Diagnostic and Statistical Manual]]), a psychiatric textbook.
* Ondine's Curse was mentioned in the medical horror novel ''[[The M.D.]]'' by [[Thomas Disch]] in which an unscrupulous doctor with the power of Mercury's caduceus cursed a stolen purse: "Take the money from this purse, and you will suffer ''Ondine's Curse''".
==References==
{{Reflist|2}}
{{CNS diseases of the nervous system}}
{{SleepSeries2}}
[[Category:Abnormal respiration]]
[[Category:Pulmonology]]
[[Category:Neurology]]
[[Category:Sleep disorders]]
[[de:Undine-Syndrom]]
[[fr:Ondinisme (syndrome)]]
[[it:Ipoventilazione alveolare primitiva]]
[[nl:Ondine's vloek]]
[[ja:先天性中枢性肺胞低換気症候群]]
[[pl:Klątwa Ondyny]]