A Commentary on The importance of knowing from whence your PHOX2B mutation comes

Meguro et al.¹ have more fully characterized the growing cohort of patients with Congenital Central Hypoventilation syndrome (CCHS) in Japan. Specifically, they have confirmed the autosomal dominant inheritance pattern^{2, 3} and described the incidence of somatic mosaicism or full mutation in parents of CCHS probands in the Japanese cohort (22%)—reflecting similar figures to the report (using the same methodology) as Bachetti et al.⁴

Finally, identification of a cohort of this size in a Japanese population raises further questions about the actual incidence of CCHS worldwide. With the 2010 ATS Statement on CCHS, the international figure of 1000 cases was presented (though presumed to be an underestimate). Ethnic disparity among reported individuals with CCHS is apparent, with Caucasians more heavily represented than any other ethnicity.⁶ Additionally, the incomplete penetrance and variable phenotype identified here and elsewhere in individuals with the 20/25 genotype indicates there may be a growing number of individuals with unrecognized mild hypoventilation who will necessitate clinical acumen and intellectual curiosity to identify. As knowledge of this disease spreads and utilization of PHOX2B testing escalates, the perceived ‘rareness’ of CCHS may prove overstated.

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