Osteoporosis-pseudoglioma syndrome, autosomal recessive (OPPG)

(OMIM phenotype number #259770)

Osteoporosis-pseudoglioma syndrome, autosomal recessive, (OPPG) is a very rare disease caused by homozygous or compound heterozygous mutation in the gene encoding low density lipoprotein receptor-related protein-5 (LRP5), with loss of LRP5 function and decreased osteoblast activity. OPPG is characterized by congenital or infancy-onset blindness and extremely severe childhood-onset osteoporosis (lumbar spine Z-score often <-4) with spontaneous fractures. Radiographs disclose severe diffuse demineralization and often reveal fractures. The eye phenotype is secondary to defective vascularization and ranges from congenital phthisis bulbi to milder vitreoretinal changes. Ocular and skeletal abnormalities predominate, although other organs may be involved also. Other clinical manifestations may include: microphthalmos, abnormalities of the iris, lens or vitreous, cataracts, short stature, microcephaly, ligamental laxity, mental retardation and hypotonia. Usually mental development is normal but ∼25% have cognitive impairment. The phenotype is variable even among siblings. The prevalence is approximately 1/2.000.000.

Few data are available on the treatment of osteoporosis in OPPG, however some beneficial response to bisphosphonates have been described.

Gene

LRP5 gene, 11q13.1 (OMIM gene/locus number *603506)

Phenotype

Blindness, microphthalmia, vitreoretinal abnormalities, cataract, phthisis bulbi, absent anterior eye chamber, iris atrophy, pseudoglyoma, muscle hypotonia, obesity, mental retardation (in some cases), ligament laxity, severe osteoporosis, multiple fractures, short stature, kyphoscoliosis, hyperextensible joints, and wide metaphyses.

Images

a b

Fig. (a) Persistence of the fibrovascular system (pseudoglioma) visible upon funduscopy. (b) Standard radiograph of the lumbar spine in a 37-year-old man with OPPG. Note the extremely severe demineralization and multiple vertebral fractures (Levasseur R, Lacombe D, de Vernejoul MC. LRP5 mutations in osteoporosis-pseudoglioma syndrome and high-bone-mass disorders. Joint Bone Spine. 2005 May;72(3):207-14.). 

Reproduced from Br J Ophthalmol, Wilson G, Moore A, Allgrove J, volume 85, page 1139, copyright notice 2001 with permission from BMJ Publishing Group Ltd.
 

Other resources

References

  1. Levasseur R, Lacombe D, de Vernejoul MC. LRP5 mutations in osteoporosis-pseudoglioma syndrome and high-bone-mass disorders. Joint Bone Spine. 2005 May;72(3):207-14.
  2. Laine CM, Chung BD, Susic M, et al. Novel mutations affecting LRP5 splicing in patients with osteoporosis-pseudoglioma syndrome (OPPG).
  3. Eur J Hum Genet. 2011 Aug;19(8):875-81.
  4. Streeten EA, McBride D, Puffenberger E, et al. Osteoporosis-pseudoglioma syndrome: description of 9 new cases and beneficial response to bisphosphonates. Bone. 2008 Sep;43(3):584-90.
  5. Gong Y, Slee RB, Fukai N, et al. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. 2001 Nov 16;107(4):513-23.
  6. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Jun 13.
  7. http://www.omim.org