Late-onset central hypoventilation syndrome: a family genetic study.

Congenital central hypoventilation syndrome is a rare disorder characterised by chronic alveolar hypoventilation, which becomes more pronounced during sleep and may be associated with neurocristopathies, such as Hirchsprung's disease. A mutation in the PHOX2B gene has recently been identified. In a family of both parents and five offspring, detailed clinical assessment, pulmonary function testing, overnight sleep studies and ventilatory responsiveness to progressive hypercapnia (V'(R,CO(2))) were performed, in addition to analysis of known genetic loci for this condition. The father and four of the offspring demonstrated features of central hypoventilation with nonapnoeic oxygen desaturation during sleep and diminished V'(R,CO(2)), despite normal pulmonary function. The lowest sleep saturation was median (range) 79% (67-83%) and V'(R,CO(2)) was 2.1 (0.03-4.3) L x min(-1) x kPa(-1). The normal values for the authors' centre (St Vincent's University Hospital, Dublin, Ireland) are 15-40 L x min(-1) x kPa(-1). An in-frame five amino acid polyalanine expansion of the PHOX2B gene was found in all affected subjects, while the mother and fifth child, who did not have features of central hypoventilation, had a normal PHOX2B gene. Magnetic resonance imaging of the brainstem in one severely affected child was normal. The present study of a unique family confirms that transmission of late-onset congenital central hypoventilation syndrome is autosomal dominant in nature.

Home mechanical ventilation.

A postal survey assessed the role of home mechanical ventilators (HMV) in the management of chronic respiratory failure in the Irish Republic. The survey collected information on indications for therapy, investigations performed and patient follow-up. Surveys were sent to all centres identified as prescribing HMV and were completed by February 2002, relating to the situation existing on July 1st 2001. From a total of 52 preliminary surveys, 14 centres (including two paediatric) were identified as prescribing HMV. A total of 157 patients used HMV and 67 (43%) were initiated on HMV during the 12 months prior to the survey. There were more males than females (86[55%] v 71[45%]) and most (61%) were in the 25-65 age bracket. The causes of respiratory failure were lung diseases (41%), thoracic cage deformities (33%), and neuromuscular diseases (26%). The majority of HMV users (95%) were prescribed pressure-cycled ventilators. The survey identified inadequate procedures for follow-up of patients on HMV and an over-reliance on equipment suppliers for patient support.