Definition

These two conditions arise from disruption of the same FGF23 pathway in opposite directions. Gain-of-function variants in the FGF23 gene make FGF23 resistant to proteolytic degradation, raising circulating active FGF23 levels; this reduces renal phosphate reabsorption, leading to hypophosphatemic rickets/osteomalacia. Loss-of-function variants in the PHEX gene cause X-linked hypophosphatemic rickets, the most common form of hereditary rickets. In contrast, loss-of-function of FGF23 or variants in GALNT3/KL lead to hyperphosphatemic tumoral calcinosis, characterized by ectopic calcium-phosphate deposits.

Gene/region examined

FGF23 - Exon 1, FGF23 - Exon 2, FGF23 - Exon 3

Method

Sequence analysis

Accepted sample types

EDTA blood, AF, CVS

Inheritance

Hereditary; the PHEX-related form is X-linked dominant; FGF23-related hypophosphatemic rickets is autosomal dominant; hyperphosphatemic tumoral calcinosis (FGF23/GALNT3/KL) is autosomal recessive.

Related Tests

Inheritance Patterns

Describes how a genetic condition is passed on within a family. There are five main patterns

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Carrier (Heterozygous / Homozygous)

Why it matters: In autosomal recessive inheritance, when each parent is a carrier (while both appear healthy), the chance of their child being born with the disease is 25% in each

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VUS (Variant of Uncertain Significance)

This is the situation where the test has detected a change in the DNA, but the role of this change in the development of disease is unconfirmed.

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How to Read a Genetic Test Result (Positive / Negative / VUS)

A genetic test result falls into three main categories

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Types of Genetic Tests

A genetic test is a type of medical test that detects changes in genes, chromosomes or proteins. Today there are more than 77,000 genetic tests available.

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