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Connective tissue diseases

Last updated: November 11, 2020

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Connective tissue is an important biological tissue composed of an extracellular matrix that binds, anchors, and supports organs. There are various types of connective tissue, all of which consist of varying combinations of fibers, cells, and intercellular substance. Over 200 conditions, which may be inherited or autoimmune, affect connective tissue, and they are collectively known as connective tissue diseases (CTDs). Inherited CTDs are caused by mutations that affect one of the two fibers (collagen and fibrillin). Autoimmune CTDs have no clear etiology, but the incidence is higher in women and among genetically predisposed individuals. As the name suggests, in autoimmune CTDs, the immune system develops antibodies against components of connective tissue. Individual conditions can affect a vast range of bodily structures (including cartilage, blood vessels, bone, tendons, and organs) and thus present with a wide array of clinical findings.

Clinical features vary greatly among individual diseases. The table below provides a general overview of the more common features.

Overview of manifestations of connective tissue disorders
Features Autoimmune CTDs Inherited CTDs
General
  • Fever, weight loss, fatigue
  • Fatigue, weakness
Musculoskeletal
  • Joint hypermobility, curved spine, brittle bones, bone deformities, growth abnormalities (short or tall stature)
Skin
  • Hyperextensive, fragile skin
Other organ manifestations

References:[2][3][4][5]

This table lists the most important connective tissue disorders and some examples of their clinical features. For more information on Marfan syndrome, Ehlers-Danlos syndrome, and osteogenesis imperfecta, see the respective articles.

Overview of inherited connective tissue disorders
Condition Etiology Pathophysiology Clinical features (examples)
Marfan syndrome
Ehlers-Danlos syndrome
  • Defective collagen cross-linking and fibril synthesis
Menkes disease [6]
  • X-linked recessive neurodegenerative disease caused by a mutation in the gene ATP7A (coding for Menkes protein, copper-transporting ATPase 1)
Osteogenesis imperfecta
Scurvy

A for Absent copper and B for a Bunch of copper: In Menkes disease, the ATP7A gene is defective, resulting in decreased copper levels. In Wilson disease, the ATP7B gene is defective, which leads to high copper levels.

Ehlers-Danlos syndrome and Menkes disease are both associated with reduced lysyl oxidase activity, resulting in defective collagen cross-linking and fibril synthesis.

  1. Choudhary S, Gadegone R, Koley S. Menkes kinky hair disease. Indian J Dermatol. 2012; 57 (5): p.407. doi: 10.4103/0019-5154.100503 . | Open in Read by QxMD
  2. Pauker SP. Clinical manifestations and diagnosis of Ehlers-Danlos syndromes. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-ehlers-danlos-syndromes.Last updated: July 8, 2016. Accessed: March 13, 2017.
  3. Beary JF, Chines AA. Osteogenesis imperfecta: Clinical features and diagnosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/osteogenesis-imperfecta-clinical-features-and-diagnosis.Last updated: September 3, 2015. Accessed: April 12, 2017.
  4. Kashtan CE. Clinical manifestations, diagnosis and treatment of hereditary nephritis (Alport syndrome). In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/clinical-manifestations-diagnosis-and-treatment-of-hereditary-nephritis-alport-syndrome#H4.Last updated: December 8, 2016. Accessed: April 12, 2017.
  5. Wright MJ, Connolly HM. Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/genetics-clinical-features-and-diagnosis-of-marfan-syndrome-and-related-disorders#H14.Last updated: November 2, 2016. Accessed: April 12, 2017.
  6. Loeys-Dietz syndrome. https://ghr.nlm.nih.gov/condition/loeys-dietz-syndrome#synonyms. Updated: March 1, 2017. Accessed: October 2, 2019.
  7. Herold G. Internal Medicine. Herold G ; 2014