Ondine's Curse: Causes, Symptoms, and Treatment

April 17, 2018

Ondine’s curse has long been recognized as a congenital disorder and can also develop later in life as a result of damage to the lower lateral medulla. There are only a few cases-about 200 to 500 worldwide-each year.

In the ancient mythical story, a young nymph named Ondine falls in love and marries. Upon discovering that her husband been unfaithful to her, she uses her supernatural powers to set a curse on him. Ondine’s curse is an unusual spell that sneakily robs her disloyal husband of rest. He is doomed to a life in which he retains the ability to breath-but only when he is awake and conscious. Once afflicted by Ondine's curse, the victim cannot breathe if he falls asleep-and therefore must choose between sleeping and remaining alive.

Symptoms of Ondine’s curse

The dramatic fictional tale has a real life counterpart in a rare disorder, central hypoventilation syndrome, often called Ondine’s curse. Patients who are afflicted with central hypoventilation syndrome do not have the ability to maintain regular respiration during sleep or may stop breathing during sleep. The cessation of regular breathing seen in central hypoventilation syndrome is more severe than the breathing cessation characteristic of the much more common, and less dangerous, sleep apnea.

Interruption of breathing can cause a decrease in the supply of oxygen to the body. The severity of the condition is variable, and symptoms can range from fatigue to organ damage to death.

Causes

Ondine’s curse has long been recognized as a congenital disorder and can also develop later in life as a result of damage to the lower lateral medulla. There are only a few cases-about 200 to 500 worldwide-each year. Case reports describe the acquired conditions in association with damage to the lateral medulla caused by stroke, tumors, and trauma.

A mutation, believed to be the cause of at least some cases of the congenital condition was identified almost 20 years ago. It appears to be a novel mutation of the PHOX2B gene,1 and the condition is not likely to be hereditary.

Interestingly, studies have shown that there are 2 types of PHOX2B gene mutations.2 Children with PHOX2B gene frameshift mutations also have Hirschsprung's disease and neuroblastoma and are described as having syndromic congenital central hypoventilation syndrome. Another PHOX2B mutation, a polyalanine expansion, has been described in children with isolated congenital central hypoventilation syndrome.

Early diagnosis

Due to identification of the gene, Ondine’s curse can be diagnosed as early as in utero.3 Several case reports describe prenatal diagnosis of the condition, which leads to early care and a better chance of survival, with a reduced incidence of end organ damage due to hypoxia.

Treatment

Despite advances in diagnosis, treatment of Ondine’s curse continues to rely on respiratory support, with mechanical ventilation, and sometimes, tracheostomy, as the cornerstones of treatment. Depending on the severity of the condition, life expectancy is expected to be shortened, although supportive measures are extending the survival, even for those who are most severely afflicted by the condition.

References:

1. Sasaki A, Kanai M, Kijima K, et al. Molecular analysis of congenital central hypoventilation syndrome. Hum Genet. 2003;114:22-26.

2. Di Lascio S, Benfante R, Di Zanni E. Structural and functional differences in PHOX2B frameshift mutations underlie isolated or syndromic congenital central hypoventilation syndrome. Hum Mutat. 2018;39:219-236.

3. Rajendran GP, Kessler MS, Manning FA. Congenital Central Hypoventilation syndrome (Ondine's curse): prenatal diagnosis and fetal breathing characteristics. J Perinatol. 2009;29:712-713.