Mevalonate kinase (MK)-associated diseases encompass a broad spectrum of rare auto-inflammatory conditions

all resulting from pathogenic variants in the mevalonate kinase gene (

MVK

). Their clinical manifestations are highly variable

ranging from more or less serious systemic disorders

such as hereditary recurrent fevers

to purely localized pathologies such as porokeratosis. The oldest condition identified as linked to this gene is a metabolic disease called mevalonic aciduria

and the most recent is disseminated superficial actinic porokeratosis

a disease limited to the skin. The modes of inheritance of MK-associated diseases also diverge among the different subtypes: recessive for the systemic subtypes and dominant with a post-zygotic somatic genetic alteration for

MVK

-associated porokeratosis. This review quickly retraces the historical steps that led to the description of the various MK-associated disease phenotypes and to a better understanding of their pathophysiology

then summarizes and compares the different genetic mechanisms involved in this group of disorders

and finally discusses the diverse causes that could underlie this phenotypic heterogeneity.