Congenital Hyperparathyroidism

Hyperparathyroidism is defined as an excess of parathyroid hormone (PTH) levels in the blood, due to a prolonged overactivity of one or more parathyroid glands. Primary hyperparathyroidism (PHPT) is caused by an idiopathic defect of parathyroid growth and/or function, and it can manifest as sporadic disease or, more rarely, within the context of congenital genetic disorders (about 5% of cases). Congenital PHPT can manifest as an isolated disease (nonsyndromic inherited PHPT) or in the context of specific syndromes in association with other endocrine and nonendocrine clinical manifestations (syndromic inherited PHPT). Nonsyndromic inherited PHPT includes Familial Hypocalciuric Hypercalcemia (FHH), Neonatal Severe Primary Hyperparathyroidism (NSPHPT), and Familial Isolated Hyperparathyroidism (FIHP), while syndromic inherited PHPT includes Hyperparathyroidism-Jaw Tumor Syndrome (HPT-JT), Multiple Endocrine Neoplasia Type 1 (MEN1), Multiple Endocrine Neoplasia Type 2A (MEN2A), and Multiple Endocrine Neoplasia Type 4 (MEN4). Except for NSPHPT that is an autosomal recessive severe disease, PHPT in all the other genetic disorders is inherited as an autosomal dominant tract by the affected parent, independently by sex, with a transmission risk of 50% to both male or female offspring. Penetrance and clinical characteristics of PHPT are variable, in mutation carriers, among different diseases. Clinical and therapeutic management differs between various forms of congenital PHP. In this light, the differential diagnosis, supported by genetic testing, could be of importance to design the correct curative pathway for the patient.