Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) with ocular involvement due to a novel...

Claudin-16 (CLDN16) and claudin-19 (CLDN19) are essential tight junction proteins in the kidney that are critical for magnesium homeostasis. Mutations in CLDN16 and CLDN19 cause Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC), a rare autosomal recessive tubular disorder. The disorder can progressively lead to severe complications, including end-stage renal disease. Affected individuals often present with polyuria, polydipsia, nephrolithiasis, hematuria, muscular tetany, seizures, and failure to thrive. Notably, CLDN19 mutations have also been associated with ocular abnormalities. We describe three patients with FHHNC and ocular involvement harboring a novel homozygous variant of uncertain significance (VUS) in the CLDN19 gene (c.-24_47dup). Our findings contribute to the expanding genetic landscape of this rare disorder and highlight the importance of early diagnosis and multidisciplinary management.