Table 3.

Genetic syndromes associated with primary hyperparathyroidism

Genetic defect/Inheritance	Chromosomal location	Clinical Manifestations	Parathyroid pathology
MEN1/AD	See above	Can present very young with parathyroid tumors; 17% less than 21 years old have symptomatic hypercalcemia	Hypercalcemia first manifestation in 90%, multigland disease (microadenomatosis)
MEN2A/AD	See above	See above	Parathyroid tumors in 20% (hyperplasia/adenoma)
MEN2B (3)/AD	See above	See above	Rare
MEN4	See above	See above	Parathyroid tumors (adenomas)
FHH1/FHH2/FHH3/AD	3q21.1/19p13/19q13.2-q13.3 CASR/GNA11/AP2S1	Hypercalcemia	PTH-independent decreased calcium excretion
NSHPT/AR	3q21.1 (homozygous or compound heterozygous mutations of CASR gene)	Severe neonatal hypercalcemia, hypotonia, fatal by 3 months untreated	Urgent parathyroidectomy; multigland hyperplasia
FIHP/AD	11q13/1q31.2/3q21.1/6p24.2	Hereditary primary hyperparathyroidism without other tumors, hypercalcemia after first decade; diagnosis of exclusion	Parathyroid tumors
HPT-JT/AD	1q31.2 (CDC73; cell division cycle 73, parafibromin)	Multiple parathyroid tumors, ossifying fibromas of jaw, renal cysts perhaps other renal tumors	Adenomas, synchronous/asynchronous parathyroid tumors, lifetime risk of parathyroid carcinoma 20%, PC cause of hypercalcemia in 15–37.5%), PC reported in adolescents