A Germline ZFX Missense Variant in a Patient With Primary Hyperparathyroidism

Area of Science:

• Endocrinology
• Genetics
• Oncology

Background:

• Primary hyperparathyroidism (PHPT) is a common endocrine disorder.
• PHPT management typically involves parathyroidectomy.
• Genetic factors can predispose individuals to PHPT.

Observation:

• A 51-year-old woman with a history of PHPT, osteoporosis, and learning disability presented with recurrent hypercalcemia.
• Physical examination revealed dysmorphic features, multiple nevi, and scoliosis.
• Laboratory tests confirmed hypercalcemia and elevated parathyroid hormone (PTH) levels.

Findings:

• The patient underwent successful parathyroidectomy, normalizing calcium and PTH levels.
• Genetic testing identified a de novo heterozygous missense variant (p.R764W) in the ZFX gene.
• ZFX gene variants are associated with X-linked intellectual disability, congenital anomalies, and PHPT.

Implications:

• This case highlights a potential genetic link between ZFX variants, PHPT, and developmental anomalies.
• ZFX gene testing may be beneficial for patients with PHPT and congenital anomalies, even without a family history.
• Further research is warranted to establish ZFX as a diagnostic marker for specific PHPT subtypes.