Heritable Diseases of Connective Tissue

Heritable Diseases of Connective Tissue

KEY POINTS

Heritable disorders of connective tissues are a genetically diverse group of disorders and are associated with extreme variation in height, from very short individuals (dwarves) to those with tall stature.

The osteochondrodysplasias or skeletal dysplasias are a group of more than four hundred fifty distinct disorders frequently associated with profound short stature and orthopedic complications.

These disorders are diagnosed based on radiographic, clinical, and molecular criteria.

There has been significant progress in elucidating the underlying molecular mechanisms in most of these disorders, providing for improved clinical diagnosis and reproductive choices for affected individuals and their families.

Treatment options have been used in osteogenesis imperfecta, metabolic storage disorders, and Marfan syndrome, which may improve the quality of life and life span in affected individuals.

Heritable disorders of connective tissues are a heterogenous group of disorders characterized by abnormalities in skeletal tissues, which include cartilage, bone, tendon ligament, and muscle. Disorders of connective tissues have been classified based on clinical findings and molecular criteria. They are subclassified into those that primarily affect cartilage and bone, which are the skeletal dysplasias, and those that have a more profound effect on connective tissue, which include the Ehlers-Danlos syndrome, Marfan syndrome, and other disorders caused by abnormal extra-cellular matrix molecules, such as cutis laxa syndrome resulting from mutations in the gene that encodes fibulin five. The skeletal dysplasias are associated with abnormalities in the size and shape of the appendicular and axial skeleton and frequently result in disproportionate short stature. Until the early nineteen sixties, most individuals with short stature were considered to have pituitary dwarfism, achondroplasia (short-limbed dwarfism), or Morquio disease (short-trunked dwarfism). Presently, there are more than four hundred fifty well-characterized disorders that are classified primarily on the basis of clinical, radiographic, and molecular criteria. Disorders of connective tissues are genetic in origin and result from mutations in genes that encode extra-cellular matrix proteins, transcription factors, tumor suppressors, signal transducers, enzymes, chaperones, intra-cellular binding proteins, R N A-processing molecules, ciliary proteins, and genes of unknown function.

SKELETAL DYSPLASIAS

The skeletal dysplasias, or osteochondrodysplasias, are defined as disorders associated with a generalized abnormality in the skeletal. Although each skeletal dysplasia is relatively rare, collectively the birth incidence of these disorders is almost one in five thousand. These disorders range in severity from precious arthropathy to perinatal lethality caused by pulmonary insufficiency. Individuals with these disorders can have significant complications, including orthopedic, neurologic, and psychological. Many of these individuals seek medical attention for orthopedic complaints from ongoing pain, arthritic complaints in large joints, and back pain primarily caused by ongoing abnormalities in bone, cartilage, tendons, and ligaments.