What is Familial Tumoral Calcinosis?

Familial tumoral calcinosis (FTC) is a rare genetic disorder. FTC causes important minerals in your body to build up, leading to unusually high calcium and phosphate levels in softer tissues.¹ This includes joints, muscles and your skin. As a result of mineral buildup, hard lumps form, which are quite painful. These lumps are called calcifications, which means calcium deposits. They are more often found in larger joints, for example, the hips, elbows or shoulders. They are commonly found in those areas, but can also form in other areas of the body. 

Causes of Familial Tumoral Calcinosis

FTC is caused by changes in certain genes which control the level of phosphate in the body. ² Phosphate is needed in the body as it helps to produce energy, promotes bone health and is needed for cells to function. Usually, phosphate levels are controlled by the kidneys, the small intestines, as well as a few different hormones. These processes help to make sure any extra phosphate is absorbed, stored or removed from the body. 

However, in FTC, the mutations in the genes mean that the phosphate levels are no longer balanced. It causes there to be too much phosphate present in the blood. This is known as hyperphosphatemia. The extra phosphate present in the blood binds to calcium, creating hard deposits that stay in soft tissues instead of where they are supposed to be, in the bones. 

What genes are involved?

A gene is a short section of your DNA, found on chromosomes. Genes carry the information that determines how you look and who you are. They are passed down to you from your parents and between generations. Their job is to make all the different proteins the human body needs to function.³ It is these genes that are changed to cause FTC. The most common genes that are affected include:⁴

• Fibroblast Growth Factor 23 (FG23) - this gene controls the phosphate levels by signalling to the kidneys to remove the extra phosphate into urine. Changes to this gene means extra phosphate remains in the body instead of being removed
• Polypeptide N-Acetylgalactosaminyltransferase 3 (GALNT3) - this gene alters FG23 to make sure it is working properly. When this gene mutated, there is less FG23, so again, more phosphate builds up
• Klotho (KL) - this gene works with FG23 to maintain phosphate levels. Mutations of this gene are less common but have been linked to FTC

How is it passed down?

FTC is inherited and passed down through an autosomal recessive pattern. This means that to get FTC, a person must inherit the mutated gene from both parents. If they only get one copy of the mutated gene, they won’t get FTC, however, they will be a carrier for the condition. This means they will have no symptoms but can pass the gene on to their children.⁵

Environmental and lifestyle factors

FTC is usually a genetic condition, but certain aspects of how you live affect how severe the disease is. These factors include the following:⁶

• Phosphate intake - foods that contain a lot of phosphate can make symptoms worse. Some of these foods include fizzy drinks, dairy products (e.g., milk and cheese) and processed meats. These foods can increase the level of phosphate in the blood, meaning more calcium deposits are likely to form
• Kidney function - the kidneys help to filter out and remove excess phosphate. If someone has a kidney problem, such as chronic kidney disease, their symptoms are likely to be worse
• Vitamin D and Calcium - Vitamin D helps to absorb phosphate and calcium. Too much vitamin D can cause more deposits to form. This is also the case for calcium
• Hydration - Being dehydrated can cause kidney damage and, as a result, cause the phosphate levels to increase. Staying hydrated can help keep the kidneys healthy
• Injuries and inflammation - Parts of the body that are injured or inflamed are more likely to have calcium deposits
• Other health conditions - conditions that affect phosphate and calcium levels, like metabolic disorders, can also trigger FTC, making symptoms harder to deal with 

Genetic testing For FTC

To test and diagnose FTC, genetic testing is used to find any genes that have mutated and are linked to FTC. These genes have been mentioned above. These tests help medical professionals reach their diagnosis, especially in individuals who have unusually high levels of potassium. There are two types of tests:⁷

• Next-Generation Sequencing (NGS) - this test looks at many genes at once to identify any defective genes. This is often done when there are unusually high levels of phosphate with no known cause
• Targeted Mutation Analysis - this looks at genes that have been linked to FTC. This is especially helpful when FTC runs in a family

How are these tests done?

Firstly, a blood or saliva sample is taken. These samples are then taken to a lab to be analysed. The DNA in the sample is checked for any abnormalities in the genes that can be linked to FTC. A specialist then examines the results. If any mutations are found, that person will be guided on what the next steps are. Advice is given on how to manage the condition, and further tests may be offered to family members. These genetic tests give doctors crucial information that helps to diagnose and treat FTC.

Management and treatment for Familial Tumoral Calcinosis

FTC is managed by focusing on symptoms to stop more calcium deposits from forming.⁸ By helping to relieve symptoms, a better quality of life can be achieved. There is no cure, so instead, treatment focuses on using medicine and making lifestyle changes to manage the disorder. Furthermore, in some cases, surgery is a potential option to remove larger deposits. It is important to regularly monitor those affected by this condition so treatment plans can be adjusted. 

Medical intervention

• Phosphate binders - phosphate levels can be reduced through medication. These drugs work by binding to the phosphate in food to stop it from entering the digestive system. This means they cannot be absorbed, so there is less phosphate in the body
• Dietary changes - having a diet made up of low phosphate food is very important in managing FTC. People should also avoid food that contains high levels of calcium and vitamin D, as these can make the calcium deposits worse

Surgical intervention

• Surgery may be needed if someone has large calcium deposits that are causing a lot of pain. If this pain affects day-to-day living, surgery can be done to remove these deposits
• Surgery is only considered as a last resort, as these deposits may reform even after removing them

Monitoring and follow-up care

• Regular follow-up appointments are needed to monitor how fast the illness is spreading, and treatments may need to be changed accordingly
• Follow-up care can be made up of blood tests, imaging to see any deposits and look at how well joints are working
• These appointments and regular check-ups can help prevent any complications, such as limited movement or infections

Genetic counselling

Genetic counselling plays an important role in helping patients and families affected by FTC. Genetic counselling can help patients understand what FTC is, what testing is available, and ultimately make informed decisions about their health. It gives essential support for dealing with the emotional, ethical, and practical aspects of living with a genetic disorder.

Genetic counselling helps individuals and families understand the genetic basis of FTC, how it is inherited, and the likelihood of passing it on to future generations. It guides patients in interpreting test results, understanding available management strategies, and addressing any uncertainties about the condition.⁸

What happens during the counselling process?

Risk assessment

• The patient’s medical and family history is looked at, and genetic mutations that may run in the family are the main focus
• These together help doctors make an informed decision to decide how likely someone is to have FTC or be a carrier for the disorder

Test results

• A specialist in genetics explains the results and will let you know if you have FTC, if you are a carrier, or if you are not impacted at all
• Results from blood tests and saliva will also be assessed to confirm a diagnosis of FTC
• They will also explain how this affects other family members and what it may mean for future children
• Counselling can be given, which involves discussing future options. For example, thinking about future pregnancies, which might require extra prenatal care
• It will also help by giving more practical information on how to manage the condition

Ethical Considerations

• You must give informed consent before any testing is done.
• Patients must be aware of any risks involved.
• Patients must make their own decisions without feeling forced to make a particular choice.

Psychological Support

• Counsellors help patients and families cope with the emotional and psychological impacts of FTC, such as anxiety, guilt, or stress
• They provide ongoing support, helping individuals navigate the challenges of living with a genetic condition

Summary

Familial Tumoral Calcinosis (FTC) is a rare but serious genetic condition that may affect you or someone in your family. It leads to painful calcium deposits in soft tissues due to high phosphate levels in the blood, caused by inherited gene mutations. While there is no cure, understanding the condition, getting proper genetic testing, and making lifestyle changes—like adjusting your diet—can help manage symptoms. If you or a loved one are experiencing signs or have a family history, early diagnosis and support through genetic counselling can make a significant difference in living well with FTC.