Primary hyperparathyroidism in young patients in Russia: high frequency of hyperparathyroidism-jaw tumor syndrome.

BACKGROUND

Primary hyperparathyroidism (PHPT) is a relatively rare disorder among children, adolescents and young adults. Its development at an early age is suspicious for hereditary causes, though the need for routine genetic testing remains controversial.

OBJECTIVE

To identify and describe hereditary forms of PHPT in patients with manifestation of the disease under 40 years of age.

DESIGN

We enrolled 65 patients with PHPT diagnosed before 40 years of age. Ten of them had mutation, and PHPT in them was the first manifestation of multiple endocrine neoplasia type 1 syndrome.

METHODS

The other fifty-five patients underwent next-generation sequencing (NGS) of a custom-designed panel of genes, associated with PHPT (, , , , , , , , ). In cases suspicious for gross deletions multiplex ligation-dependent probe amplification was performed.

RESULTS

NGS revealed six pathogenic or likely pathogenic germline sequence variants: four in c.271C>T (p.Arg91*), c.496C>T (p.Gln166*), c.685A>T (p.Arg229*) and c.787C>T (p.Arg263Cys); one in c.3145G>T (p.Glu1049*) and one in c.784-9G>A. In two patients, MLPA confirmed gross deletions. In total, 44 sporadic and 21 hereditary PHPT cases were identified. Parathyroid carcinomas and atypical parathyroid adenomas were present in 8/65 of young patients, in whom mutations were found in 5/8.

CONCLUSIONS

Hereditary forms of PHPT can be identified in up to 1/3 of young patients with manifestation of the disease at <40 years of age. Parathyroid carcinomas or atypical parathyroid adenomas in young patients are frequently associated with mutations.