Hyperparathyroidism-jaw tumor syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Hyperparathyroidism-jaw tumor syndrome is a condition characterized by overactivity of the parathyroid glands (hyperparathyroidism). The four parathyroid glands are located in the neck and secrete a hormone that regulates the body's use of calcium. Hyperparathyroidism disrupts the normal balance of calcium in the blood, which can lead to kidney stones, thinning of the bones (osteoporosis), nausea, vomiting, high blood pressure (hypertension), weakness, and fatigue. About 95 percent of people with hyperparathyroidism-jaw tumor syndrome will develop hyperparathyroidism during their lifetime.

In people with hyperparathyroidism-jaw tumor syndrome, hyperparathyroidism is caused by tumors that form in the parathyroid glands. Typically, only one of the four parathyroid glands is affected, but in some people, tumors are found in more than one gland. The tumors are usually a noncancerous (benign) type of tumor called an adenoma. Approximately 15 percent of people with hyperparathyroidism-jaw tumor syndrome develop a cancerous tumor called parathyroid carcinoma.

People with hyperparathyroidism-jaw tumor syndrome may also have a type of benign tumor called a fibroma in the jaw. Even though jaw tumors are specified in the name of this condition, it is estimated that only 11 to 40 percent of affected individuals have this symptom.

Other tumors, both benign and cancerous, are often seen in people with hyperparathyroidism-jaw tumor syndrome. For example, tumors of the uterus occur in up to 50 percent of people with this condition. Uterine tumors are typically benign, but they can cause heavy menstrual bleeding or other symptoms. The kidneys are affected in about 20 percent of people with hyperparathyroidism-jaw tumor syndrome. Benign kidney cysts are the most common kidney feature, but a rare cancerous tumor called Wilms tumor and other types of kidney tumor have also been found.

Regular medical screening may assist in the early detection of the features of hyperparathyroidism-jaw tumor syndrome.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also called mutations) in the CDC73 gene cause hyperparathyroidism-jaw tumor syndrome. The CDC73 gene provides instructions for making a protein called parafibromin. This protein is found throughout the body and is likely involved in gene transcription, which is the first step in protein production. Parafibromin is also thought to play a role in cell growth and division (proliferation). It can either promote or inhibit cell proliferation depending on signals within the cell.

CDC73 gene variants cause hyperparathyroidism-jaw tumor syndrome by reducing the amount of functional parafibromin that is produced. Most of these variants cause the cell to produce a parafibromin protein that is abnormally short and does not function well. The uncontrolled cell proliferation that occurs without functional parafibromin can lead to the formation tumors. It is unknown why only certain tissues seem to be affected by changes in parafibromin.

Some people with hyperparathyroidism-jaw tumor syndrome do not have any of the variants in the CDC73 gene that are known to cause this condition. The cause of the condition in these individuals is unknown.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The exact prevalence of hyperparathyroidism-jaw tumor syndrome is unknown. Approximately 200 cases have been reported in the medical literature. It is estimated that up to 30 percent of individuals with parathyroid carcinoma have hyperparathyroidism-jaw tumor syndrome.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormality of the parathyroid morphology · Very frequent (99-80%)

A structural abnormality of the parathyroid gland.

Elevated circulating parathyroid hormone level · Very frequent (99-80%)

An abnormal increased concentration of parathyroid hormone.

Hypercalcemia · Obligate (100%)

The concentration of calcium in the blood circulation is above the upper limit of normal.

Hypophosphatemia · Very frequent (99-80%)

The concentration of phosphate ion in the blood circulation is below the lower limit of normal.

Parathyroid adenoma · Obligate (100%)

A benign tumor of the parathyroid gland that can cause hyperparathyroidism.

Primary hyperparathyroidism · Obligate (100%)

A type of hyperparathyroidism caused by a primary abnormality of the parathyroid glands (e.g., adenoma, carcinoma, hyperplasia). Primary hyperparathyroidism is associated with hyercalcemia.

Hypercalciuria · Very frequent (99-80%)

Dysphagia · Frequent (79-30%)

Difficulty in swallowing.

Other findings in the same source

From: Orphanet

Additional reported features include Fatigue (Frequent (79-30%)); Fibroma (Frequent (79-30%)); Nephrocalcinosis (Frequent (79-30%)); Nephrolithiasis (Frequent (79-30%)); Osteoporosis (Frequent (79-30%)); Polydipsia (Frequent (79-30%)); Shortened QT interval (Frequent (79-30%)); Uterine leiomyoma (Frequent (79-30%)); Bone pain (Occasional (29-5%)); Chondrocalcinosis (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Hyperparathyroidism-jaw tumor syndrome is Endocrinology, with a endocrinologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which hormone or metabolic finding is important in this case?
• How should test timing and current medicines be taken into account?
• What follow-up would show whether the care plan is working?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Hyperparathyroidism-jaw tumor syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.