Osteoporosis pseudoglioma syndrome

An autosomal recessive condition caused by homozygous or compound heterozygous inactivating mutation(s) in the gene LRP5, encoding low-density lipoprotein receptor-related protein 5.

Clinical features

This condition is characterized by severe juvenile-onset osteoporosis and congenital or juvenile-onset blindness due to a vascularized retinal mass that resembles a glioma.

What is LRP5?

Low-density lipoprotein receptor-related protein 5 is a protein that in humans is encoded by the LRP5 gene.

Significant of LRP5

LRP5 is a key component of the LRP5/LRP6/Frizzled co-receptor group that is involved in canonical Wnt pathway.

Mutations of LRP5

Mutations in LRP5 can lead to considerable changes in bone mass. A loss-of-function mutation causes osteoporosis-pseudoglioma (decrease in bone mass), while a gain-of-function mutation causes drastic increases in bone mass.

Incidence

It is a rare condition that affects one in 2 million.

Diagnosis

Diagnosis is via a combination of clinical features, history, physical examination, and genetic testing.

In people with this condition, osteoporosis is usually recognized in early childhood. It is caused by a shortage of minerals, such as calcium, in bones (decreased bone mineral density), which makes the bones brittle and prone to fracture.

Clinical presentation

Affected individuals often have multiple bone fractures, including in the bones that form the spine (vertebrae). Multiple fractures can cause collapse of the affected vertebrae (compressed vertebrae), abnormal side-to-side curvature of the spine (scoliosis), short stature, and limb deformities. Decreased bone mineral density can also cause softening or thinning of the skull (craniotabes).

Impaired vision

Most affected individuals have impaired vision at birth or by early infancy and are blind by young adulthood. Vision problems are usually caused by one of several eye conditions, grouped together as pseudoglioma, that affect the light-sensitive tissue at the back of the eye (the retina), although other eye conditions have been identified in affected individuals. Pseudogliomas are so named because, on examination, the conditions resemble an eye tumor known as a retinal glioma.

Other symptoms

Rarely, people with osteoporosis-pseudoglioma syndrome have additional signs or symptoms such as mild intellectual disability, weak muscle tone (hypotonia), abnormally flexible joints, or seizures.

Treatment

Treatment is supportive and include early detection and treatment of osteoporosis and other supportive measures.

NIH genetic and rare disease info

• NIH info on Osteoporosis pseudoglioma syndrome

Osteoporosis pseudoglioma syndrome is a rare disease.

Resources

Frequently asked questions

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