Hereditary primary hyperparathyroidism (PHPT) is a monogenic autosomal disorder, constituting 5–10% of all PHPT cases. Data on hereditary PHPT in the Chinese population are scarce.

This study aimed to delineate the etiology, phenotype, genotype, management, and prognosis of hereditary PHPT in Tianjin Medical University General Hospital, expanding the spectrum of pathogenic genes and evaluating the age-dependent penetrance of clinical phenotypes. Additionally, genotype-phenotype correlations were explored in multiple endocrine neoplasia type 1 (MEN1).

A retrospective analysis of medical records from January 1st, 2008 to July 31st, 2024 included clinical presentations, biochemical markers, imaging findings, and whole exome sequencing.

The study comprised 73 cases. MEN1 was predominant (80.8%), followed by hyperparathyroidism-jaw-tumor syndrome (9.6%), familial hypocalciuric hypercalcemia (5.5%), MEN2A (2.7%), and familial isolated hyperparathyroidism (1.4%). The male:female sex ratio was 1:1.6. Thirty patients (41.1%) exhibited multiglandular parathyroid involvement. Genetic testing in 57 patients identified 12 novel mutations, with 70.2% harboring pathogenic or likely pathogenic variants. Mean age at initial presentation for PHPT mutation carriers was 42.0±14.5 years, with 64.3% penetrance by 45 years of age. No significant genotype-phenotype correlations were observed for MEN1 mutations.

This case series provided insight into the clinical phenotypes and mutational spectrum of hereditary PHPT, emphasizing the role of genetic testing for subtype classification, complications monitoring, treatment guidance and family surveillance. Genetic testing is recommended for PHPT patients with early-onset, complex clinical presentations, multiglandular parathyroid involvement or family history.