High bone mass (HBM) / Osteopetrosis, Autosomal Dominant 1 (OPTA1)

(OMIM phenotype number #607634)

Osteopetrosis is an inherited disorder with a variety of genetic causes, resulting in abnormally high bone mass for dysfunctional bone remodeling. This bone disease is divided into two main groups: autosomal recessive and autosomal dominant types. The autosomal dominant form of osteopetrosis is less severe and often discovered in young to middle aged adults. There are two types of autosomal dominant forms. The osteopetrosis, autosomal dominant type 1 (OPTA1) is extremely rare and secondary to a defect of the LRP5 (low density lipoprotein receptor 5), causing an increased uniform sclerosis. The disease commonly has onset in late childhood or adolescence, and primarily involves the cranium. Clinical signs can include: chronic bone pain and disorders of the cranial nerves, such as trigeminal neuralgia, facial palsy, and hearing loss. Diagnosis is based on clinical and radiographic evaluation. Radiographically, the hallmark of osteopetrosis is increased density within the medullary portion of the bone with relative sparing of the cortices. In OPTA1, there is an uniform sclerosis of the long bones, skull, and spine.

The treatment is primarily supportive. In the future, the gene therapy may play a role in the future with an identifiable gene defect.

Gene

LRP5 gene, 11q13.2 (OMIM gene/locus number #603506).

Phenotype

Increased bone density, mostly asymptomatic (rarely bone pain).

Image

Fig. A patient affected by OPTA1. Chest radiograph obtained in an infant demonstrates overall increased density of the osseous structures due to the accumulation of immature bone.

Reproduced from Scarsbrook Ihde LL, Forrester DM, Gottsegen CJ, et al., Sclerosing bone dysplasias: review and differentiation from other causes of osteosclerosis, Radiographics 2011;31:1865-82 with permission from The Radiographical Society of North America.

Other resources

Osteopetrosis Society ( OPETS)

References

  1. Bollerslev J, Henriksen K, Nielsen MF, et al. Autosomal dominant osteopetrosis revisited: lessons from recent studies. Eur J Endocrinol. 2013 Jul 13;169(2):R39-57.
  2. Kirkland JD, O'Brien WT. Osteopetrosis - Classic Imaging Findings in the Spine. J Clin Diagn Res. 2015 Aug;9(8):TJ01-2.
  3. De Vernejoul MC, Kornak U. Heritable sclerosing bone disorders: presentation and new molecular mechanisms. Ann N Y Acad Sci. 2010 Mar;1192:269-77.
  4. Ihde LL, Forrester DM, Gottsegen CJ, et al. Sclerosing bone dysplasias: review and differentiation from other causes of osteosclerosis. Radiographics. 2011 Nov-Dec;31(7):1865-82.
  5. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Nov;26(11):2717-8.
  6. http://www.omim.org