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CASE REPORT |
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| Year : 2013 | Volume
: 19
| Issue : 2 | Page : 270-272 |
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Sclerosterosis (Truswell-Hansen disease)
S Deepak Amalnath, M Vivekanandan
Department of Medicine, Indira Gandhi Medical College and Research Institute, Pondicherry, India
| Date of Web Publication | 5-Aug-2013 |
Correspondence Address:
S Deepak Amalnath
Department of Medicine, Indira Gandhi Medical College and Research Institute, Pondicherry
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/0971-6866.116109
 Abstract | | |
Sclerosteosis or Truswell-Hansen disease is a rare autosomal recessive disorder characterized by dense bones, tall stature, and syndactyly. Most of the reports are from South Africa. Here we report the first such case from India.
Keywords: Sclerosteosis, Truswell-Hansen disease, dense bones, syndactyly
How to cite this article:
Amalnath S D, Vivekanandan M. Sclerosterosis (Truswell-Hansen disease). Indian J Hum Genet 2013;19:270-2 |
| Introduction | |  |
Sclerosteosis is a rare autosomal recessive disorder characterized by dense bones, tall stature, and syndactyly. Most of the reports are from South Africa. We report one such pedigree from South India and briefly discuss the genetics of this rare disorder.
| Case Report | | |
A 50-year-old man, diabetic for the past 10 years, presented with poorly controlled diabetes and cataract. Incidentally, he had coarse facial features with frontal bossing and congenital left facial nerve palsy with facial synkinesia [Figure 1]. He also had syndactyly of the left 3 rd and 4 th fingers and short right 4 th finger along with hypoplastic nails [Figure 2]. Radiographs showed dense skull [Figure 3], pelvis [Figure 4], lumbar spine, and fingers. Serum calcium, phosphorus, and alkaline phosphatase were normal.
He was born of a consanguineous marriage and the granddaughter of his elder brother was operated for syndactyly [Figure 5]. His family members could not be examined.
| Discussion | | |
The clinical picture of dense bones, congenital facial palsy, syndactyly, and an autosomal recessive pattern closely fits the diagnosis of sclerosteosis (Truswell-Hansen disease). Sclerosing bone dysplasias refer to group of bone disorders characterized by dense bones. There are four types of hyperostosis corticalis generalisata. [1] Worth disease and Nakamura disease are autosomal dominant disorders characterized by benign course and localized involvement of the facial bones. Van Buchem disease and sclerosteosis are autosomal recessive disorders characterized by generalized bone sclerosis and progressive course.
Sclerosteosis was initially described as osteopetrosis with syndactyly. [2]
Van Buchem disease and sclerosteosis are closely related disorders, differentiated by the presence of syndactyly, increased height and rapid progression in the later. Sclerosteosis is of two types. Type 1 is due to mutation of the SOST gene coding for sclerostin and has been mapped to 17q12-q21. [3] Type 2 is due to mutation of LRP 4 gene [4] (low-density lipoprotein receptor-related protein) located at 11p11.2.
Sclerostin is secreted by osteocytes and it down regulates osteoblasts by inhibiting the Wnt pathway mediated b-catenin release. Sclerostin causes the internalization of LRP5; the co receptor of Wnt. LRP4 facilitates the interaction of sclerostin with Wnt. Van Buchem disease is also caused by mutations in the downstream regulator of sclerostin. Loss of function of sclerostin leads to increased osteoblastic activity. [3] Inhibitors of sclerostin are being tried in the treatment of osteoporosis.
Most of the reported patients of sclerosteosis are from the Afrikanar population [5] (descendants of the Dutch settlers) of South Africa. To our knowledge, this is the first such report from India.
| Conclusion | | |
sclerosteosis is a very rare disorder, the study of its genetics has helped in understanding the various regulators of bone remodeling and may have a therapeutic role in the treatment of osteoporosis and other bone disorders.
| References | | |
| 1. | Ihde LL, Forrester DM, Gottsegen CJ, Masih S, Patel DB, Vachon LA, et al. Sclerosing bone dysplasias: Review and differentiation from other causes of osteosclerosis. Radiographics 2011;31:1865-82. 
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| 2. | Truswell AS. Osteopetrosis with syndactyly: A morphological variant of Albers-Schönberg's disease. J Bone Joint Surg Br 1958;40-B: 209-18.
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| 3. | Balemans W, Ebeling M, Patel N, Van Hul E, Olson P, Dioszegi M, et al. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet 2001;10:537-43.
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| 4. | Leupin O, Piters E, Halleux C, Hu S, Kramer I, Morvan F, et al. Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function. J Biol Chem 2011;286:19489-500.
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| 5. | Hamersma H, Gardner J, Beighton P. The natural history of sclerosteosis. Clin Genet 2003;63:192-7.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
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