Osteoporosis-Pseudoglioma Syndrome

Clinical Characteristics
Ocular Features: 

Retrolental masses often present at birth have been mistaken for retinoblastomas.  Hyperplasias of the vitreous, corneal opacities, and secondary glaucoma have been described.  Band keratopathy may account for some of the corneal clouding and opacities.  Most patients are blind soon after birth although some retain some vision into the second decade.

Systemic Features: 

Some patients have been described as mentally retarded but others have normal intelligence.  Hypotonia and hyperflexible joints have been noted.  Bone fractures are common sometimes resulting in scoliosis, short stature and limb deformities.  Radiography of the skeletal reveals porotic and thin bones.

Genetics

This disorder, sometimes called the ocular form of osteogenesis imperfecta, results from mutations in LRP5 (11q13.4).  The same gene is mutant in the EVR4 type of familial exudative vitreoretinopathy (601813) which has some of the same ocular and bone features.  Most descriptions of OPPG were published before the gene mutation was found and many reports do not include detailed ocular examinations.  Certainly the two disorders are allelic and likely the same condition. 

Mutations in LRP5 lead to EVR4 disease in both the heterozygous and homozygous configuration but most cases of OPPG have homozygous or compound heterozygous mutations.

Treatment
Treatment Options: 

Bone fractures need to be repaired and glaucoma treated when present.  Bisphosphonate treatment may lead to increased bone density if initiated early.  The retrolental masses need to be carefully evaluated to rule out retinoblastoma.

References
Article Title: 

Osteoporosis-pseudoglioma syndrome, a disorder affecting skeletal strength and vision, is assigned to chromosome region 11q12-13

Gong Y, Vikkula M, Boon L, Liu J, Beighton P, Ramesar R, Peltonen L, Somer H, Hirose T, Dallapiccola B, De Paepe A, Swoboda W, Zabel B, Superti-Furga A, Steinmann B, Brunner HG, Jans A, Boles RG, Adkins W, van den Boogaard MJ, Olsen BR, Warman ML. Osteoporosis-pseudoglioma syndrome, a disorder affecting skeletal strength and vision, is assigned to chromosome region 11q12-13. Am J Hum Genet. 1996 Jul;59(1):146-51.

PubMed ID: 
8659519

References

Streeten EA, McBride D, Puffenberger E, Hoffman ME, Pollin TI, Donnelly P, Sack P, Morton H. Osteoporosis-pseudoglioma syndrome: description of 9 new cases and beneficial response to bisphosphonates. Bone. 2008 Sep;43(3):584-90.

PubMedID: 18602879

Gong Y, Vikkula M, Boon L, Liu J, Beighton P, Ramesar R, Peltonen L, Somer H, Hirose T, Dallapiccola B, De Paepe A, Swoboda W, Zabel B, Superti-Furga A, Steinmann B, Brunner HG, Jans A, Boles RG, Adkins W, van den Boogaard MJ, Olsen BR, Warman ML. Osteoporosis-pseudoglioma syndrome, a disorder affecting skeletal strength and vision, is assigned to chromosome region 11q12-13. Am J Hum Genet. 1996 Jul;59(1):146-51.

PubMedID: 8659519

Somer H, Palotie A, Somer M, Hoikka V, Peltonen L. Osteoporosis-pseudoglioma syndrome: clinical, morphological, and biochemical studies. J Med Genet. 1988 Aug;25(8):543-9.

PubMedID: 3172149