Familial isolated hyperparathyroidism

The investigation of familial isolated hyperparathyroidism (FIHP) has been greatly facilitated in recent years by the identification of the genes responsible for most cases of syndromic familial hyperparathyroidism (HPT). Kindreds with apparently isolated hyperparathyroidism have been evaluated with clinical, biochemical, imaging and gene mutational tests designed to recognize multiple endocrine neoplasia type 1 (MEN1), the hyperparathyroidism-jaw tumor syndrome (HPTJT), and familial hypocalciuric hypercalcemia (FHH). Approximately 100 kindreds with the apparent diagnosis of FIHP were studied in clinical series that included screening by germline DNA mutational testing of one or more of the genes for these three syndromes since 1997. Of these provisionally diagnosed FIHP kindreds, some 10 to 20% had occult MEN1 and roughly 10% each had unrecognized HPT-JT or an FHH-related disorder evidenced by mutation of the calcium sensing receptor. Thus nearly 70% of FIHP kindreds are apparently non-syndromic. Even accounting for the likely underestimation in this group of syndromic causes for familial HPT due to shortcomings in current clinical and gene mutational testing methods, this finding suggests the majority of FIHP kindreds have no currently recognized syndromic etiology. Further study of this subset of carefully evaluated and apparently non-syndromic FIHP kindreds should assist in the identification of novel gene(s) important for neoplasia in the parathyroid and whose mutation can result in the FIHP phenotype.