Disorder
Osteoporosis-pseudoglioma syndrome

Clinical Characteristics

General description (for patients):

This is another type of “brittle bones” found among plain people.  In contrast to the more common ‘osteogenesis imperfecta’ condition (see osteogenesis imperfecta type I)  in which the only eye involvement is a blue color to the white of the eyes, in osteoporosis-pseudoglioma syndrome there is severe ocular involvement and blindness is inevitable.  Bone fractures are frequent due to severe thinning and loss of calcium in skeletal bones.  Mild shortness of stature is variably present.  Mental functioning is usually normal.  Some drugs for osteoporosis may be helpful, especially if started early.

Medical description (for healthcare providers):

This brittle bone disorder differs from the more common variety of osteogenesis primarily in the virtually inevitable occurrence of blindness due to vitreoretinal abnormalities known as FEVR (familial exudative vitreoretinopathy) caused by another mutation in the same gene in a minority of FEVR patients.   A noticeably shortened stature has been seen in a minority of OPPG patients, and a few have mild mental delays and behavioral problems. OPPG results from a mutation that interferes with normal bone modeling, resulting in severe juvenile-onset osteoporosis.  Those with the most severe disease can suffer multiple fractures resulting in marked deformities.

Genetics:

This autosomal recessive condition results from a mutation in the LRP5 gene on chromosome 11 (11q13.4) that interferes with normal binding of the low-density lipoprotein receptor-related protein-5.  Two mutations in this gene, known as W425X and T409A, have been identified among Mennonites in Pennsylvania.  Both mutations were found segregating in a single pedigree, with the more severe disease resulting from homozygosity of W425X, and milder bone disease in compound heterozygotes (no homozygous T409A individuals were found).  However, blindness secondary to retinal detachments occurred in all patients with both genotypes.  Heterozygotes with both mutations also can have mild osteoporosis.

Management:

Bisphosphonate treatment can improve bone density, and should be started early.  The importance of trauma avoidance should be emphasized for all patients.  Vitamin D insufficiency should be treated.  At the moment there is no treatment for the vitreoretinal disease and blindness seems to be inevitable.

Low vision evaluations and mobility training are of more than the usual importance in this disorder for obstacle avoidance and prevention of falls.  Prompt orthopedic treatment and protective body equipment are important.

Prognosis:

Long term follow-up is lacking in this rare disorder.  However, repeated fractures can lead to deformity disabilities.

Specialists and specialty centers:

Orthopedist, Endocrinologist, Ophthalmologist, Low Vision Specialist.

References:

Streeten, E.A., McBride, D., Puffenberger, E., Hoffman, M.E., Pollin, T.I., Donnelly, P., Sack, P., and Morton, H.: Osteoporosis-pseudoglioma syndrome: Description of 9 new cases and beneficial response to bisphosphonates.  Bone43: 584-590, 2008.  PubMed ID: 18602879

Beighton, P., Winship, I., and Behari, D.:  The ocular form of osteogenesis imperfecta: a new autosomal recessive syndrome.  Clin. Genet. 28: 69-75, 1985.  PubMed ID: 4028503

Zacharin, M., and Cundy, T.,  Osteoporosis pseudoglioma syndrome: treatment of spinal osteoporosis with intravenous bisphosphonates.  J. Pediatr. 137: 410-415, 2000.  PubMed ID: 10969269

Resources:

Osteogenesis Imperfecta Foundation
National Osteoporosis Foundation