An unusual presentation of congenital central hypoventilation syndrome (Ondine's Curse)
- Correspondence to Dr R E Bullock, Regional Centre for Neurosciences, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne, UK;
- Accepted 23 March 2009
Congenital central hypoventilation syndrome is a rare illness, which classically presents in the neonatal period; newborns present with shallow breathing and cyanosis, without a physiological rise in breathing rate. Incidence has been estimated from 1 in 10 000 to 1 in 200 000 live births. This case report describes the case of a young man who was asymptomatic until his presentation in acute respiratory failure at the age of 36 years. This case is reported to highlight the importance of considering this treatable illness as a potential cause of collapse and respiratory failure in adults presenting to emergency departments.
A 36-year-old man was admitted to the emergency department following a collapse at a restaurant. He had consumed 6 units of alcohol over the course of the evening. On initial assessment his Glasgow coma score was 3/15 and he was afebrile. Bloods tests were normal (haemoglobin 13.5 g/dl, platelets 165, white cell count 7.0, sodium 138, potassium 4.6, urea 5.6, creatine 60, C-reactive protein <1). Arterial blood gases on room air showed a marked respiratory acidosis, with a raised bicarbonate (pH 7.24, partial pressure carbon dioxide (Pco2) 10.0, partial pressure oxygen (Po2) 9.5, bicarbonate 32.1). When the patient was placed on 15 litres oxygen, the acidosis worsened (pH 7.11, Pco2 14.8, Po2 41.6). The patient was subsequently intubated.
Full cardiovascular, respiratory and neurological examination was normal. Chest x-ray was normal. His only past medical history of note was of a constitutional growth delay during adolescence; this was fully investigated at the time, and no endocrine pathology was found.
Subsequent oximetry showed episodes of profound desaturations and carbon dioxide retention. The patient had an apnoea/hypopnoea index of 21.4/h (the number of desaturations was >4% below baseline per hour). At worst, his oxygen saturation fell to 59% and carbon dioxide rose to 10.5 kPa. Repeat oximetry, when the patient was ventilated with bilevel positive airways pressure, demonstrated satisfactory oxygen saturation and carbon dioxide levels throughout sleep. A magnetic resonance brain imaging scan was undertaken and was normal, showing no brainstem abnormalities.
Investigations were undertaken to look for a primary neuromuscular, lung, cardiac or brainstem pathology that may account for his clinical findings. More detailed magnetic resonance brain imaging with fine cuts through the brainstem was normal. Detailed nerve conduction studies and electromyography, including examination of the phrenic nerve and diaphragm, were normal. Echocardiography showed normal heart structure and function.
Further questioning of the patient revealed a lifelong normal sleep pattern. He denied daytime somnolence or headache, to suggest any previously undiagnosed nocturnal hypoventilation. The only thing of note was a very poor tolerance to alcohol, and he had been monitored overnight in a police cell on two previous occasions after becoming unresponsive after relatively small amounts.
Genetic testing was performed, as 50–98.5% of congenital central hypoventilation syndrome (CCHS) patients have mutations of the paired-like homeobox 2b (PHOX2B) gene.1 It was revealed that he is heterozygous for a polymorphism (about 870C→A) known to be associated with CCHS.1
Ondine's Curse is a reference to the myth of Ondine, 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.
Failure of automatic control of breathing is rare; in adults mass lesions within the brainstem may cause symptoms, but in infants and children it is usually congenital (CCHS) and is often but not always associated with mutations in the PHOX2B gene. These patients develop marked oxygen desaturation and carbon dioxide retention during sleep.2 In our patient, a brainstem mass lesion was carefully excluded and despite his age a diagnosis of CCHS was made.
There are case reports of CCHS presenting in adulthood. However, many of these reports note that patients have histories of being extraordinary breath-holders as toddlers, of becoming cyanosed but not distressed by hypoventilation, or being able to swim underwater longer and further than their peers.3 Also, presentation to a doctor usually follows years of poor sleeping and evidence of decreased rapid eye movement and non-rapid eye movement sleep. This classically includes daytime somnolence, morning headaches and frequent napping, none of which had been experienced by our patient.
In order to make a clinical diagnosis of CCHS, it is essential first to rule out a primary neuromuscular, lung, or cardiac pathology, or brain stem lesion. In addition, the patient must have evidence of alveolar hypoventilation, particularly during sleep, poor sensitivity to hypercapnia and hypoxia without a concomitant rise in respiratory rate and lack of psychological or behavioural awareness of developing hypoxia.
A variety of treatments have been used including ventilation and diaphragmatic pacing. There are long-term survivors who have used bilevel positive airways pressure for many years, showing that nocturnal ventilation has good long-term outcomes and may even permit a normal lifespan.3
With reference to the patient's history of growth hormone deficiency as an adolescent, it remains uncertain whether this is a relevant connection to his ultimate neurological diagnosis. A search of published medical literature reveals only two previous cases of adult-onset CCHS in patients with growth hormone deficiency.4 There is no current evidence that these two illnesses share a common pathogenic process, but hypothalamic dysfunction has been suggested to play a role.
The episodes of collapse in association with excess alcohol are likely to be relevant in our patient, and it is worth highlighting the need for considering arterial blood gases in patients with decreased consciousness level secondary to alcohol.
Our patient has responded extremely well to home nocturnal ventilation and is able to live a full and active lifestyle.
This case report highlights a late onset presentation of CCHS in a previously well adult. Although this is a rare cause of respiratory failure in an emergency department, it is crucial to consider and exclude CCHS as a cause for this presentation given the treatable nature of the condition.
Competing interests None.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.