Familial hypomagnesemia with hypercalciuria and nephrocalcinosis in three siblings having the same genetic lesion but different clinical presentations

Background: This article summarizes the varying clinical manifestations of three siblings with familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) caused by the same genetic lesion. Methods: The medical records of three siblings with FHHNC (one girl and two boys, aged 6 to 12 years) were reviewed and the clinical manifestations and treatment of their disease were described. Results: Despite varying phenotypes, each sibling had the same genetic lesion a novel homozygous mutation in CLDN16 (c.211A>G, M71V). Conclusion: Although FHHNC is a rare disorder, this report is significant for the following reasons: (i) it describes a novel CLDN16 mutation causing FHHNC, adding to the literature of FHHNC-causing CLDN16 mutations; (ii) it suggests that genes other than CLDN16 or epigenetic factors are involved in the clinical spectrum of FHHNC; and (iii) it reinforces the variability of disease manifestation and genotype-phenotype correlations. World J Pediatr 2012;8(2):177-180