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Skeletal dysplasias: Specific disorders

Author
Carlos A Bacino, MD, FACMG
Section Editor
Sihoun Hahn, MD, PhD
Deputy Editor
Elizabeth TePas, MD, MS

INTRODUCTION

The skeletal dysplasias are an extremely heterogeneous group of conditions that affect bone development. They encompass over 400 disorders [1]. Most are the result of genetic defects. Skeletal dysplasias can present any time from the prenatal period to adult life. The estimated incidence of skeletal dysplasias is approximately 15.7 in 100,000 births.

The classification of these disorders and the understanding of their pathophysiology have improved over time due to the advent of molecular studies and gene discoveries. This knowledge has contributed to the development of treatment options for specific skeletal dysplasias, such as achondroplasia, hypophosphatasia, and osteogenesis imperfecta.

A few of the most common conditions are reviewed in brief here, with some reviewed in greater detail separately. The diagnostic evaluation of the lethal and nonlethal skeletal dysplasias is discussed separately. (See "Prenatal diagnosis of the lethal skeletal dysplasias" and "Skeletal dysplasias: Approach to evaluation".)

ACHONDROPLASIA AND HYPOCHONDROPLASIA

Achondroplasia is the most common skeletal dysplasia in humans and is associated with a recurrent mutation in the trans-membrane domain of the fibroblast growth factor receptor 3 (FGFR3) gene (recurrent mutations are de novo mutations that occur repeatedly in a population in the general vicinity of a particular gene). The most salient clinical features include disproportionate short stature, long bone shortening that predominantly affects the proximal aspects of the upper and lower extremities, and macrocephaly. Hypochondroplasia is another allelic disorder that is associated with FGFR3 mutations, although the mutations in this disorder occur in the cytoplasmic (immunoglobulin-like) domain. These patients have milder clinical manifestations than achondroplasia, with some similar radiologic findings. (See "Achondroplasia".)

DYSOSTOSIS MULTIPLEX

Skeletal changes can be seen in some storage metabolic disorders, such as the mucopolysaccharidoses, mucolipidoses, or gangliosidoses. In these conditions, the bone changes are secondary to progressive storage of complex carbohydrates (glycoproteins or glycolipids) slowly accumulating in the lysosomes and affecting cartilage and bones. This progressive accumulation leads to bone changes known as dysostosis multiplex. Dysostosis multiplex is evidenced by flattening of the vertebrae and, in some cases, anterior protrusion of the vertebral bodies. Other changes include widening of the ribs (paddle rib deformities) such as in mucolipidoses, long bone remodeling, and metacarpal proximal pointing. (See "Mucopolysaccharidoses: Clinical features and diagnosis", section on 'MPS type IV (Morquio syndrome)' and "Mucopolysaccharidoses: Clinical features and diagnosis", section on 'Hurler syndrome'.)

                                    

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Literature review current through: Nov 2016. | This topic last updated: Fri Oct 28 00:00:00 GMT+00:00 2016.
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