Congenital central hypoventilation syndrome (CCHS) is a rare disorder of respiratory control characterized by ventilatory impairment that results in arterial hypoxemia. Although patients typically present this disease as newborns and rarely in later infancy, there have been reports of patients presenting with CCHS in adulthood.

The present study reports a unique familial case in which the father (proband) presented late-onset CCHS with an expansion mutation of the Phox2B gene that was confirmed by genetic analysis. Surprisingly, the proband did not report any manifestation of the disease during childhood, and the disease progressed following an insidious course until adulthood. At the time of diagnosis, he did not present signs of pulmonary hypertension and right-side heart failure. The patient responded well to nocturnal invasive ventilation. In contrast, his son presented CCHS as a newborn with the full complement of symptoms while his daughter did not.

The present report shows that CCHS cases characterized by a mutated Phox2 gene can progress without many symptoms and that the treatment approach used here was efficient for controlling the course of the disease. Furthermore, this case indicates that incomplete penetrance can occur. Genetic screening of family members is mandatory to evaluate the reproductive risk of the disease, especially because asymptomatic mutation carriers may be at high risk to develop the disease and transmit it to the next generation.

Congenital central hypoventilation syndrome (CCHS) is a rare disorder of respiratory control characterized by ventilatory impairment that results in arterial hypoxemia. This condition worse during sleep and occurs in patients with normal mechanical properties of the lung. It is diagnosed in the absence of primary neuromuscular disease, identifiable brainstem lesions, and other sleep disturbances or substance use.

Amiel et al. (2003) identified a mutation in the Phox2B gene associated with CCHS, characterized by 5 to 9 alanine expansions within a 20-residue polyalanine region in exon 3 of the Phox2B gene. Several reports confirmed the findings of Amiel et al., supporting the view that this gene is a master switch for the development of the autonomic nervous system network linked to respiratory control. Transgenic animals carrying the human Phox2B mutation develop a similar phenotype and lack glutamatergic neurons located in the parafacial region in the brainstem, which are involved in breathing control.

Although patients typically present with CCHS as newborns and rarely in later infancy, there have been reports of patients presenting with CCHS in adulthood. In cases of late-onset CCHS, most patients report having had some symptoms since childhood, and they have parents with a history of CCHS. Symptoms of right-side heart failure are generally observed at the time of diagnosis, and nocturnal noninvasive ventilation is frequently indicated.

The present study reports a unique familial case of CCHS in which the father (proband) presented late-onset CCHS linked to a Phox2B gene expansion mutation. The presentation, course of development and treatment response for this patient was unique His son presented CCHS as a newborn, while his daughter did not.

Inclusion Criteria:Family member

Exclusion Criteria:NA

familial case in which the father (proband) presented late-onset CCHS with an expansion mutation of the Phox2B gene that was confirmed by genetic analysis.