New Concepts About Familial Isolated Hyperparathyroidism.

CONTEXT: Familial isolated hyperparathyroidism (FIHP) is defined as familial primary hyperparathyroidism (FH) without a characteristic extra-parathyroidal feature of a more complex hyperparathyroid syndrome. During 80 years, new concepts of FIHP have been developed within this definition. FIHP has been difficult to study due to small kindreds and mildly symptomatic cases. EVIDENCE ACQUISITION: Searches were through PubMed for FIHP, other FH syndromes, and the gene(s) mutated in each. EVIDENCE SYNTHESIS: Within its definition, the current concept of FIHP has clinical and mutational components. It can include incomplete expressions of MEN1 FHH, or HPT-JT or their mutations. Newest concepts of FIHP focus upon kindreds without mutation of either the MEN1, CASR, or CDC73 gene; 17% have germline activating mutation of the gene for the GCM2 transcription factor. Other genes for FIHP will probably be identified shortly. The FIHP kindreds with or without GCM2 mutation contain a median of only 2 cases of PHPT. The small kindred size in both subgroups of FIHP is probably caused low rate of screening among relatives. PHPT in FIHP with GCM2 mutation seems similar to PHPT in MEN1. Persons with FIHP and GCM2 mutation present as adults with mild hypercalcemia and multiple parathyroid tumors.
CONCLUSIONS: The current concept of FIHP led to a focus on small kindreds without mutation of MEN1, CASR, or CDC73. These assisted in the identification of germline activating GCM2 mutations in 17%. There is a need for clinical and mutational characterization in more cases to determine any unique clinical features of FIHP, either with or without mutation of GCM2.