What Is Skeletal Dysplasia?

What is skeletal dysplasia? It is a group of related conditions which are genetically transmitted and which affect the structure of bones and cartilage. This can determine the appearance of the sufferer, most noticeably in a reduction in expected height attainment, and also in bodily proportions which may be altered from the norm. The number of sufferers of dysplasias as an entire group has been quoted at approximately four million worldwide.[1].

Some forms of dysplasia are fatal and others have a proportion of fatalities: others are non-lethal. Even so, skeletal abnormalities can still cause difficulties for the sufferer, and a number of other conditions are often associated with dysplasias e.g. heart problems.[2] Intellectual development is usually normal although there are certain exceptions.[3]

Different dysplasias have been found to have involvement of a variety of genes in their transmission, although there may be some overlap which makes diagnosis more difficult.

Genetic mutations in the following genes are just a few that have been identified: -

COMP gene - codes for a structural protein that is part of the extracellular matrix of cartilage

FGFR3 - codes for fibroblast growth factor receptor 3 that binds growth factors. Mutations lead to increased activation

MATN3 - the protein forms part of the extracellular matrix of cartilage

Genetic testing may be put to use in order to confirm the exact dysplasia a sufferer has, where specific gene involvement is known, but radiography, histochemical (tissue) analyses, ultrasonography (prenatally) and clinical assessment may all also have a role to play in provision of a differential diagnosis.

These can help e.g. in the use of histochemical analysis to identify whether bone tissue, cartilage or growth plate are affected, or radiography to identify which part of the skeleton has been malformed. Biochemical assays may be put to use e.g. where dysplasias with abnormal lipid or sugar metabolism are suspected.[3].

Ultrasonography and radiography can provide pre-natal clues e.g. limb length, which can assist in the production of a pre-natal diagnosis: pre-natal diagnoses of fatal skeletal dysplasias have been quoted as higher than 80%.[3] Symptoms presented may not be exclusive to a specific dysplasia which can make diagnosis complex.

What treatments are in use with regard to skeletal dysplasias? Growth hormone treatment has been used in some cases with some positive results although not all dysplasias exhibited a positive response. Surgery may also be an option in some cases.[4]

1 Jakobsen, Ingrid B., Wyeld, Theodor G., Hansen, David B., Zankl, A. 'Visualising a skeletal dysplasia knowledgebase'. Proceedings of 'BioMedical visualization'. 4th International Conference on Medical Information Visualization (MediViz07), Zurich, Switzerland, 04-06 July 2007, pp. 43-47.

2 S R Ahuja, S Karande, M V Kulkarni 'Skeletal dysplasia with unusual visceral manifestations'. Postgrad Med J. 78: 107 (2002):99-100.

3 Unger, Sheila, Superti-Furga, A., Rimoin, David L. 'A Diagnostic Approach to Skeletal Dysplasias'. International Skeletal Dysplasia Society. 2003. (20/10/2009) <http://www.isds.ch/ISDSframes.html>

4 Kanazawa, H., Tanaka, H., Inoue, M., Yamanaka,Y., Namba, N. , Seino, Y. 'Efficacy of growth hormone therapy for patients with skeletal dysplasia'. Journal of Bone and Mineral Metabolism. 21:5. (2003):307-310.