What are the early warning signs that a child might have a mutation in the FGF23 gene causing hypophosphatemic rickets?

Children may develop bone pain, bowing of the legs, growth delays, frequent fractures, or dental problems such as delayed tooth eruption. If these symptoms appear, a pediatrician may order serum phosphate, alkaline phosphatase, and urinary phosphate tests to screen for FGF23-related disorders.

Can a family history of tumoral calcinosis or bone pain indicate a need for genetic testing of the FGF23 gene?

Yes. If a parent or sibling has been diagnosed with hyperphosphatemic familial tumoral calcinosis or unexplained bone lesions, genetic counseling and testing for FGF23 mutations can confirm inheritance patterns and guide monitoring of at-risk relatives.

What dietary changes can help manage phosphate levels in patients with FGF23-related disorders?

For hyperphosphatemic conditions, limiting high-phosphate foods such as dairy, nuts, and processed meats can reduce serum phosphate. In hypophosphatemic rickets, phosphate supplements and active vitamin D analogs are prescribed; patients should follow the dosing schedule and avoid excessive calcium intake that may worsen bone mineralization.

How is the effectiveness of FGF23-targeted therapy monitored in patients with hypophosphatemic rickets?

Clinicians track serum phosphate, alkaline phosphatase, and 1,25-dihydroxyvitamin D levels every 3–6 months. Radiographs of long bones and growth plate assessment help evaluate bone healing, while symptom diaries record pain and mobility changes. Adjustments to phosphate or vitamin D dosing are made based on these results.

FGF23 Gene

The FGF23 gene encodes a protein that regulates phosphate balance in the body, and mutations can cause disorders such as hyperphosphatemic familial tumoral calcinosis and hypophosphatemic rickets.

Normal Function

The FGF23 gene provides instructions for making a protein called fibroblast growth factor 23, which is produced in bone cells. This protein helps regulate phosphate levels within the body. Among its many functions, phosphate plays a critical role in the formation and growth of bones during childhood and helps maintain bone strength in adults.

Fibroblast growth factor 23 works in the kidneys to keep the body's phosphate levels in balance. The kidneys normally release excess phosphate in the urine, and they reabsorb this mineral into the bloodstream when more is needed. Fibroblast growth factor 23 acts as a signal that tells the kidneys to stop reabsorbing phosphate into the bloodstream.

In order for fibroblast growth factor 23 to function, sugar molecules must attach to the protein through a process called glycosylation. This allows fibroblast growth factor 23 to move out of the bone cell and protects it from being broken down. Once outside the cell, fibroblast growth factor 23 must bind to a receptor protein that spans the membrane of kidney cells. Binding to this receptor triggers a signaling pathway that stops phosphate reabsorption by the kidneys. When more phosphate is needed, fibroblast growth factor 23 is cut (cleaved) at a certain site, which turns off (inactivates) the protein. This helps regulate the amount of active fibroblast growth factor 23 that is circulating in the bloodstream.

Health Conditions Related to Genetic Changes

Hyperphosphatemic familial tumoral calcinosis

Variants (also called mutations) in the FGF23 gene have been found to cause hyperphosphatemic familial tumoral calcinosis (HFTC), a condition that is characterized by increased levels of phosphate in the blood (hyperphosphatemia) and abnormal deposits of phosphate and calcium (calcinosis) in the body's tissues. Variants in the FGF23 gene can cause cells to produce a version of the protein that does not function properly. This altered protein is quickly broken down in cells, leading to a shortage of available fibroblast growth factor 23. This protein shortage decreases signaling and increases the amount of phosphate that is reabsorbed by the kidneys. The excess phosphate can combine with calcium to form deposits that build up in the tissues, leading to the calcinosis seen in people with HFTC.

Other disorders

Variants in the FGF23 gene are a rare cause of hypophosphatemic rickets. This condition is characterized by low levels of phosphate in the blood (hypophosphatemia). A lack of phosphate can cause weakening or softening of the bones. The variants in the FGF23 gene that are associated with hypophosphatemic rickets cause cells to produce a version of the protein that is not cleaved. This increases the amount of activated FGF23 protein in the blood and impairs the reabsorption of phosphate by the kidneys. This means less phosphate is available for normal bone development and maintenance, which contributes to the skeletal abnormalities seen in people with hypophosphatemic rickets.

Other Names for This Gene

Genomic Location

The FGF23 gene is found on chromosome 12.

Tests Listed in the Genetic Testing Registry

Tests of FGF23

Scientific Articles on PubMed

PubMed

Catalog of Genes and Diseases from OMIM

FIBROBLAST GROWTH FACTOR 23; FGF23

Gene and Variant Databases

NCBI Gene
ClinVar

References

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