Congenital Central Hypoventilation Syndrome (CCHS): A Case Of Late Onset Presentation

Abstract

CCHS or Ondine9s curse is a rare autosomal dominant disease, characterized by disorders of the autonomic nervous system, with abnormal ventilatory responses to hypercapnia and hypoxemia. PHOX2B has been identified as the major disease causing gene for CCHS. It results from polyalanine repeat expansion mutations. It typically occurs in the newborn period, but some cases have been described on adults (late onset CCHS) and reflects the variable penetrance of PHOX2B mutations. A 48 year-old woman presented after an ovarian cyst surgery a severe hypoventilation requiring intubation. Arterial blood gas revealed a PO2 of 50 mmHg, a PCO2 of 80 mmHg and a pH of 7,22. Past medical history indicated poor apparent symptoms for few years. These included apneas, fitfully sleep and awakening with headaches. Physical examination and pulmonary function tests, lung tomography, magnetic resonance imaging of the brainstem were normal. Polysomnography revealed many central and obstructive apneas and hypopneas (apnea-hypopnea index of 22/h) with severe hypoxemia (SpO2 average 75%) and hypercapnia (transcutaneous CO2 85mmHg). Non invasive ventilation was initially poorly tolerated. Finally, she responded to an adaptative servo ventilation. Hypoxia and hypercapnia tests showed no adaptation of the ventilatory response. Genetic analysis showed a heterozygous five alanine expansion mutation of the 20-residue polyalanine tract in exon 3 of the PHOX2B gene. The diagnosis of late onset CCHS should be considered in patients with unexplained hypoventilation after anesthesia, and physiologic evaluations documenting abnormal ventilatory response should be completed. The presence of a PHOX2B mutation confirms the diagnosis.