Genotype-based prevalence of Birt-Hogg-Dubé syndrome in the healthcare and genomic registry populations – breaking the ‘rare disease’ status?

TL;DR

This study shows that Birt-Hogg-Dubé syndrome is much more common than previously thought, especially in diverse populations.

Contribution

The study reveals that BHD-causing FLCN variants are significantly more prevalent in genomic registry populations than previously estimated.

Findings

FLCN variants are 75 to 180 times more prevalent in a multi-ethnic genomic registry population.

Current prevalence estimates for Birt-Hogg-Dubé syndrome may be outdated and underrepresent non-European populations.

The findings suggest a need for updated prevalence and penetrance estimates for BHD and similar syndromes.

Abstract

The phenotype-based prevalence of Birt-Hogg-Dubé syndrome (BHD) is commonly estimated at 1 in 200,000–500,000. However, we demonstrate that BHD-causing FLCN variants are 75 to 180 times more prevalent in the multi-ethnic large genomic registry population. We highlight the urgent need for updated prevalence and penetrance estimates for BHD and other tumor suppressor gene syndromes, particularly among underrepresented non-European populations.

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