Introduction:
Familial tumoral calcinosis was first reported in the year 1898 by two french dermatologists, Giard and Duret. Different terminologies were used to describe the condition, such as hyperphosphatemia hyperostosis, hyperphosphatemia tumoral calcinosis, and hyperphosphatemia tumoral calcinosis. Inclan et al. first coined the term tumoral calcinosis, and they mentioned it as an inherited disorder. A Familial tumoral calcinosis is a heterogeneous group of diseases in which the appearance of cutaneous and subcutaneous calcified masses occurs as a result of increased serum calcium and phosphate levels.
What Is Familial Tumoral Calcinosis?
A Familial tumoral calcinosis is a rare genetic disorder characterized by an increase in serum phosphate levels. This, in turn, would result in abnormal deposition of phosphate and calcium in the tissues of the body.
What Are the Types of Familial Tumoral Calcinosis?
Two main types of familial tumoral calcinosis have been recognized, that includes:
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Hyperphosphatemic familial tumoral calcinosis.
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Nonphosphatemic familial tumoral calcinosis.
What Is the Etiology of Familial Tumoral Calcinosis?
Hyperphosphatemic familial tumoral calcinosis is caused due to the mutation in the fibroblast growth factor 23 (FGF 23). Whereas, the nonphosphatemic type of familial tumoral calcinosis is caused due to the mutation in SAMD9 (sterile alpha motif domain containing 9), which is a tumor suppressor and an anti-inflammatory protein.
What Is the Difference Between Autosomal Dominant and Autosomal Recessive Inheritance Patterns?
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The autosomal dominant inheritance pattern occurs when only a single copy of a mutated gene is present in any one of the parents or as a result of a new mutation in the affected individual. The chance of transmitting the disease from one generation to another in each pregnancy is 50 %.
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Autosomal recessive inheritance pattern occurs when both parents carry abnormal genes, and the chance of spreading the disease from one generation to another in each pregnancy is 25 %.
What Is the Epidemiology of Familial Tumoral Calcinosis?
It is reported to be more prevalent among African and the middle east population. Most cases were reported to show autosomal dominant inheritance patterns, but a few cases were observed to show autosomal recessive inheritance patterns. Hyperphosphatemic familial tumoral calcinosis type is more common than the nonphosphatemic type of familial tumoral calcinosis. The symptoms usually develop around the first to the third decade of life.
What Is the Pathogenesis of Familial Tumoral Calcinosis?
The suggested pathogenesis of this condition is that,
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The FGF23 gene provides instructions for making a protein called a fibroblast growth factor which is responsible for regulating the phosphate levels in the body. Mutations in this gene would result in increased serum phosphate levels and increase the tubular reabsorption of phosphate from the kidneys.
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The SAMD9 gene is involved in the control of cell proliferation and has a role in tumor suppression. Deleterious mutations in this gene would result in the development of nonphosphatemic familial tumoral calcinosis by inducing the development of calcific masses in various parts of the body.
What Are the Signs and Symptoms of Familial Tumoral Calcinosis?
The symptoms include:
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Calcinosis - Is a tumor-like growth in the body tissues, which are composed of non-dividing cells. They are usually seen in periarticular soft tissues especially seen in the hips, elbows, and shoulders.
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Hyperostosis - This is the painful swelling in the areas overlying the diaphyses of the tibia, metacarpal bones, ulna, and radius.
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Vascular Calcifications - Calcification in the small and large blood vessels.
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Dental Disturbances - Such as enamel hypoplasia, pulp stones, obliteration of the pulp chambers, and short and bulbous roots.
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Testicular Microlithiasis - This is a condition in which small clusters of calcium form in the testicles. cold extremities, decreased peripheral pulses, and angioid streaks of the retina are the other symptoms.
How Is Familial Tumoral Calcinosis Diagnosed?
History:
A thorough medical and family history should be collected from the patient as it would provide a clue in the diagnosis of the condition. Family history would help in understanding the genetic link in families.
Physical Examination:
Physical examination of the patient would reveal the presence of calcified tumor masses in the elbow, hip region, etc.
Blood Test:
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Serum Phosphate Levels - This may indicate increased serum phosphate levels (hyperphosphatemia).
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Tubular Reabsorption of Phosphorus - This may indicate increased renal tubular reabsorption.
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1,25- Dihydroxyvitamin D3 - May indicate elevated or normal serum 1,25- dihydroxy vitamin D3 levels.
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Renal Function Test - Indicates normal renal function.
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C-Terminal Portion of the Phosphate-Regulating Hormone - Would be elevated.
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C-Terminal Portion of Fibroblast Growth Factor 23 (FGF23) - Would be elevated.
Plain- X-Ray Radiographic Findings:
Radiographic findings would reveal:
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Tumor calcinosis.
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Hyperostosis.
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Enamel hypoplasia.
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Thistle-shaped dental pulps.
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Abnormal curvature of the dental roots.
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Short bulbous roots.
Computed Tomography (CT):
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Tumor Calcinosis - Is indicated to measure the size and thickness of calcifications in patients with tumor calcinosis.
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Vascular Calcifications - Can be visualized through CT, where the blood vessels appear attenuated due to the presence of calcium salts.
Genetic Studies:
This would reveal the presence of mutations in the fibroblast growth factor 23 in the case of patients with hyperphosphatemic familial tumoral calcinosis and sterile alpha motif domain containing nine mutations in the case of patients with nonphosphatemic familial tumoral calcinosis.
How Is Familial Tumoral Calcinosis Managed?
The main aim of the treatment is to reduce serum phosphate levels, thereby reducing the complications of the condition. The steps in management are as follows:
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Restricting Phosphate Intake: The serum phosphate levels can be reduced by taking low phosphate-containing foods and medications.
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Increasing Renal Phosphate Excretion: Renal phosphate excretion can be increased by taking drugs such as Probenecid, Acetazolamide, and Nicotinamide.
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Surgical Resection: Surgical removal of the large tumor calcinosis lesions is advised if they are subjected to frequent irritation and damage.
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Dietary Restrictions: Diets containing excessive calcium, dietary products, phosphate binders, and vitamin D supplements should be avoided.
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Genetic Counseling: Once the disease has been diagnosed in the family with an autosomal dominant or recessive pattern of inheritance, carrier testing should be done to estimate the risk of inheritance among the family members, and prenatal testing in case of susceptible pregnancy is warranted.
What Are the Differential Diagnoses of Familial Tumoral Calcinosis?
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Autoimmune Connective Tissue Disease - Is characterized by the production of autoantibodies against the own connective tissue cells.
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Osteomyelitis - Osteomyelitis is the infection and inflammation of the bone tissue.
Conclusion:
Familial tumoral calcinosis is a rare inherited disorder with an autosomal dominant or recessive inheritance pattern. It is an incidental finding in most cases. The calcified masses develop slowly and reach a larger size. There is no specific treatment for this condition, and the treatment should be initiated to relieve symptoms. This condition shows a good prognosis with appropriate management measures.
