The skeletal dysplasias

Abstract

Abstract:The skeletal dysplasias (osteochondrodysplasias) are a heterogeneous group of more than 350 disorders frequently associated with orthopedic complications and varying degrees of dwarfism or short stature. These disorders are diagnosed based on radiographic, clinical, and molecular criteria. The molecular mechanisms have been elucidated in many of these disorders providing for improved clinical diagnosis and reproductive choices for affected individuals and their families. An increasing variety of medical and surgical treatment options can be offered to affected individuals to try to improve their quality of life and lifespan. Genet Med 2010:12(6):327-341. Generalized disorders of cartilage and bone have been referred to as skeletal dysplasias, whereas those that affect an individual bone or group of bones have been referred to as dysostoses; however, these distinctions are blurring as their basic defects are elucidated. The skeletal dysplasias are associated with abnormalities in the patterning, development, maintenance, and size of the appendicular and axial skeleton and frequently result in disproportionate short stature. Until the early 1960s, most individuals with short stature were considered to have pituitary dwarfism, achondroplasia (short-limb dwarfism), or Morquio disease (short-trunked dwarfism). Presently, there are more than 350 well-characterized skeletal dysplasias that are classified primarily on the basis of clinical, radiographic, and molecular criteria. 1 They result from mutations in various families of genes that encode extracellular matrix proteins, transcription factors, tumor suppressors, signal transducers (ligands, receptors, and channel proteins), enzymes, cellular transporters, chaperones, intracellular binding proteins, RNA processing molecules, cilia and cytoplasmic proteins, and a number of gene products of currently unknown function. The skeletal dysplasiasThe skeletal dysplasias are disorders associated with a generalized abnormality in the skeleton. Although each skeletal dysplasia is relatively rare, collectively the birth incidence of these disorders is almost 1/5000. 2 These disorders range in severity from precocious arthropathy in relatively average stature individuals to severe dwarfism with perinatal mortality. These disorders can be associated with a variety of orthopedic, neurologic, auditory, visual, pulmonary, cardiac, renal, and psychological complications. EmbryologyThe human skeleton (from the greek, skeletos, "dried up") is a complex organ consisting of 206 bones (126 appendicular, 74 axial, and 6 ossicles). The musculoskeletal system also includes tendons, ligaments, and muscles, and, in addition to cartilage and bone, is involved in linear growth, mechanical support, movement, a blood cell and mineral reservoir, and protection of vital organs. These tissues and adipocytes all derive from mesenchymal precursor cells.The patterning and architecture of the skeleton during fetal development determine the number, size, and the shape of the future skeletal elem...

Targeted next-generation sequencing identifies novel compound heterozygous mutations of DYNC2H1 in a fetus with short rib-polydactyly syndrome, type III

“…These conditions are caused by a widespread disturbance of bone growth, which begins during the early stages of fetal development and evolves throughout life due to associated genetic defects, one group of which includes short rib-polydactyly syndromes (SRPS). Despite advances in imaging technology, fetal skeletal dysplasias are difficult to diagnose in utero due to the large number of skeletal dysplasias and overlapping phenotypic features [2,3].…”

A suspected genetic form of bilateral osteochondritis dissecans of the knee in a Dutch family

“…Although the mechanism by which ACAN and COL9A2 mutations cause OCD is not fully understood, the evidence offers growing support of an important role of a disturbed ECM and endochondral ossification in both idiopathic and familial OCD [45]. The prominent dysmorphic features seen in familial OCD closely resemble the symptoms of skeletal dysplasias and diseases related to disturbed endochondral ossification, but the identified mutations are unlikely to play a role in idiopathic OCD due to the severity of the malformations [46,47].…”

Stuve-Wiedemann syndrome with a novel mutation

“…Owing to the several possible types and groups of skeletal dysplasia, which in themselves are rare diseases,1 diagnosis of specific disorders outside expert centres can be challenging. Expertise in paediatric radiology and genetics is essential in this process.…”

“…Skeletal dysplasias are rare general disorders of cartilage and bone; they result in disproportionate growth and short stature,1 with associated abnormalities in other organ systems. Their classification is based on a combination of molecular, biochemical and radiological criteria 1.…”

“…Their classification is based on a combination of molecular, biochemical and radiological criteria 1. More than 450 different skeletal dysplasias are in existence, which can be broadly classified into approximately 40 different groups based on the above diagnostic criteria 2…”