Ondine Syndrome

Rare congenital failure of autonomic control of breathing during sleep. Other features include Hirschsprung disease and reduced esophageal motility.

Congenital Central Hypoventilation Syndrome (CCHS); Ondine-Hirschsprung Disease; Ondine Curse.

The name of this syndrome originates from Old German mythology about the water nymph Ondine (Undine). Nymphs are known to be very beautiful, and Ondine was certainly no exception. Nevertheless, she was very wary of men because they are a threat to a nymph's immortality. Whenever a nymph falls in love with a man, she loses her immortality and begins to age and eventually dies. However, all this was forgotten when Ondine discovered Sir Huldbrecht, a young knight, near her lily pond. Sir Huldbrecht, too, was captured by Ondine's beauty, and soon the two fell in love and married. From this very moment, however, Ondine started to age. Her stunning beauty slowly fading away, Sir Huldbrecht soon found himself looking for a younger and prettier woman. One afternoon, Ondine caught Sir Huldbrecht happily in the arms of a young woman. Having sacrificed her immortality for this man who had sworn love and faithfulness to her, Ondine demanded retaliation. With her magic still powerful enough for vengeance, she cursed Sir Huldbrecht: “As long as you are awake, you shall have your breath, however, as soon as you fall asleep, your breath will be taken from you!” It didn't take long until Sir Huldbrecht fell asleep from exhaustion and died shortly thereafter. This myth illustrates the problem of the patient suffering from congenital central hypoventilation.

Autosomal recessive or autosomal dominant with reduced penetrance (or paternal gonadal mosaicism).

Probable anomaly of integration in the central nervous system (CNS) of afferent stimuli from peripheral chemoreceptors. The resulting hypoventilation is most pronounced during sleep, with relative insensitivity to hypercarbia and a lesser insensitivity to hypoxia. The frequent association of CCHS with Hirschsprung disease led to the hypothesis that it could be a form of neural crest disease.

Polysomnographic recordings show decreased minute ventilation during sleep with hypoxemia and hypercarbia. Acquired causes of alveolar hypoventilation should be excluded: CNS infection, metabolic disease, cerebral or brainstem malformation, myotonic dystrophy.

Breathing is usually normal when awake but marked hypoventilation occurs during sleep: respiratory rate slows down to 8 to 10 breaths per minute with long pauses. Onset is usually in the first days or weeks after birth, but precise diagnosis is often delayed. Frequent association with Hirschsprung disease (13-26%), ocular anomalies (66%), or anomalies of the autonomic cardiac control (44%). May have distinctive facies: low-set ears, small nose, triangular mouth, down-slanting palpebral fissures. Inappropriate secretion of antidiuretic hormone (ADH) has been described in a few cases. The incidence of neuroblastoma or ganglioneuroma is higher than in a control population. Pulmonary hypertension and cor pulmonale occur if sleep-induced hypoventilation is not corrected. Treatment occurs at home with positive-pressure ventilation during sleep via a tracheostomy during infancy and childhood, and a face mask afterward. Phrenic nerve pacing is being tried.

Check for the presence of cor pulmonale with echocardiography. The size of the tracheostomy tube must be noted. It is recommended not to use sedative premedication unless close monitoring is available. In case of association with Hirschsprung disease, the presence of a neuroblastoma or ganglioneuroma should be excluded (abdominal ultrasonography, urine catecholamines). The child's own ventilator should be present in the recovery room in case of respiratory depression or residual sedation.

The central nervous system respiratory response to CO2 is blunted. Perioperative O2 supplementation may exacerbate hypoventilation. Tracheal extubation must be performed when patient is fully awake. Locoregional anesthesia is recommended if appropriate for the surgical procedure. Esophageal motility could be decreased, so the risk of pulmonary aspiration is increased. Cases of inappropriate ADH secretion have been described; postoperative fluid requirements should be adapted to the patient's needs.

Increased sensitivity to the respiratory effect of opiates is probable.

Haddad Syndrome: Association of Hirschsprung disease (especially total colonic aganglionosis) with congenital central hypoventilation. Neuroblastoma or ganglioneuroma is found in nearly 20% of the cases. Other associated anomalies are ocular problems, sensorineural deafness, and disturbances of gastrointestinal motility.