The hypothesis of the influence of modulators and epigenetic factors in the clinical spectrum of FHHNC is reinforced by studies that report unusual clinical findings in FHHNC patients with CLDN16 mutations [27–29] and different clinical courses in siblings with the same CLDN16 mutation [17, 30]. Here, CLDN16 is linked to familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis.