It is a rare disease in which the outer part of the shafts of long bones is thinner than normal and there is an increased chance of fractures.

The bone abnormalities in the legs commonly cause knock knees (genu valgum) in affected individuals.

[citation needed] It is an autosomal recessive disorder in which mild clinical manifestations contrast with radiological appearances of gross metaphyseal undermodeling.

Patients may present with dental caries, mandibular prognathism, spinal alignment, and disproportionate limb lengthening.

This gene provides instructions for making a protein that blocks (inhibits) a process called Wnt signaling, which is involved in the development of several tissues and organs throughout the body.

In particular, regulation of Wnt signaling by the SFRP4 protein is critical for normal bone development and remodeling.

The resulting dysregulation of Wnt signaling leads to the bone abnormalities characteristic of Pyle disease.

[3] Pyle disease is inherited in an autosomal recessive pattern, which means both copies of the SFRP4 gene in each cell have mutations.

Segregation analysis in the patient revealed a germline mutation, resulting in reduced protein formation.