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At a glance

Inherited bone dysplasia affecting the enchondral growth of long bones, which results in failure of modeling and causes increased circumference of the ends of the shafts (Erlenmeyer-flask deformity). Chalklike appearance of bone, delayed tooth eruption.


Pyle Metaphyseal Dysplasia; Familial Metaphyseal Dysplasia. If the cranial features are significant, the disease is also called Craniometaphyseal Dysplasia.

N.B.: Metaphyseal Dysplasia and Metaphyseal Chondrodysplasia are not the same disease.


First described by Edwin Pyle (1891-1961), an American orthopedic surgeon in 1931.


About 30 cases have been reported in four families.

Genetic inheritance

Autosomal recessive.


Pyle disease is caused by homozygous mutation in the SFRP4 gene on chromosome 7p14. It encodes for a protein that acts as an antagonist to the WNT/frizzled pathway when bound to the WNT ligands or to the Frizzled receptors. Mutation in the SFRP4 activates predominantly canonical Wnt signaling in trabecular bone, leading to increased trabecular bone mass.


Made by clinical features and radiographic studies. Symmetrical expansion of the metaphyses of long bones results in the so-called “Erlenmeyer flask deformity,” describing the flaring of long bones (mainly of distal femur and proximal tibia) in combination with cortical thinning in affected areas. This sign is typical, but not pathognomonic, because it can also be seen in osteopetrosis, Niemann-Pick, and Gaucher diseases. Osteoporosis of the long bones with an increased risk for fractures is common.

Clinical aspects

The patient may be clinically asymptomatic. The patients are almost always tall as a result of increased limb length (especially femur and tibia). The most frequent clinical feature is genu valgum, which is usually mild but may predispose to fractures. The elbows may not fully extend, the proximal humerus is abnormally wide, as are the distal radius and ulna. The widening of the lower end of the femurs may be palpable. There is a gross defect in metaphyseal modeling. Radiologic examination of the spine may reveal platyspondyly, which could be attributed to either the same defect in modeling seen in the metaphyses of the long bones or to pathological fractures as a result of osteoporosis. Scoliosis has been reported in some patients. The head is enlarged with diffuse hyperostosis of the entire cranial vault, bony encroachment on the cranial foramina (potentially resulting in nerve compression with visual and hearing impairment/loss), absent or poorly pneumatized paranasal sinus, significantly thickened bone in the area of the glabella with hypertelorism, and often obstructed nasal breathing (breathing difficulties during upper airway infections have been described). Inconsistently, the presence of deciduous teeth is prolonged with marked cavities and prognathia may be present. Intelligence and general health are ...

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