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Scleroderma, familial progressive

MedGen UID:
356661
Concept ID:
C1866983
Disease or Syndrome
Synonyms: SYSTEMIC SCLEROSIS, SUSCEPTIBILITY TO
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
 
OMIM®: 181750

Definition

Systemic sclerosis is a clinically heterogeneous connective tissue disorder characterized by immune activation, vascular damage, and fibrosis of the skin and major internal organs. Clinical and experimental data suggest that the disorder is multifactorial, involving both genetic and environmental factors (Fonseca et al., 2007). Gabrielli et al. (2009) provided a detailed review of scleroderma, including clinical manifestations and pathophysiology. See also Reynolds syndrome (613471), which shares some clinical features with scleroderma and CREST syndrome. [from OMIM]

Additional description

From GHR
Systemic scleroderma is an autoimmune disorder that affects the skin and internal organs. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. The word "scleroderma" means hard skin in Greek, and the condition is characterized by the buildup of scar tissue (fibrosis) in the skin and other organs. The condition is also called systemic sclerosis because the fibrosis can affect organs other than the skin. Fibrosis is due to the excess production of a tough protein called collagen, which normally strengthens and supports connective tissues throughout the body.The signs and symptoms of systemic scleroderma usually begin with episodes of Raynaud phenomenon, which can occur weeks to years before fibrosis. In Raynaud phenomenon, the fingers and toes of affected individuals turn white or blue in response to cold temperature or other stresses. This effect occurs because of problems with the small vessels that carry blood to the extremities. Another early sign of systemic scleroderma is puffy or swollen hands before thickening and hardening of the skin due to fibrosis. Skin thickening usually occurs first in the fingers (called sclerodactyly) and may also involve the hands and face. In addition, people with systemic scleroderma often have open sores (ulcers) on their fingers, painful bumps under the skin (calcinosis), or small clusters of enlarged blood vessels just under the skin (telangiectasia).Fibrosis can also affect internal organs and can lead to impairment or failure of the affected organs. The most commonly affected organs are the esophagus, heart, lungs, and kidneys. Internal organ involvement may be signaled by heartburn, difficulty swallowing (dysphagia), high blood pressure (hypertension), kidney problems, shortness of breath, diarrhea, or impairment of the muscle contractions that move food through the digestive tract (intestinal pseudo-obstruction).There are three types of systemic scleroderma, defined by the tissues affected in the disorder. In one type of systemic scleroderma, known as limited cutaneous systemic scleroderma, fibrosis usually affects only the hands, arms, and face. Limited cutaneous systemic scleroderma used to be known as CREST syndrome, which is named for the common features of the condition: calcinosis, Raynaud phenomenon, esophageal motility dysfunction, sclerodactyly, and telangiectasia. In another type of systemic scleroderma, known as diffuse cutaneous systemic scleroderma, the fibrosis affects large areas of skin, including the torso and the upper arms and legs, and often involves internal organs. In diffuse cutaneous systemic scleroderma, the condition worsens quickly and organ damage occurs earlier than in other types of the condition. In the third type of systemic scleroderma, called systemic sclerosis sine scleroderma ("sine" means without in Latin), fibrosis affects one or more internal organs but not the skin.Approximately 15 percent to 25 percent of people with features of systemic scleroderma also have signs and symptoms of another condition that affects connective tissue, such as polymyositis, dermatomyositis, rheumatoid arthritis, Sjögren syndrome, or systemic lupus erythematosus. The combination of systemic scleroderma with other connective tissue abnormalities is known as scleroderma overlap syndrome.  https://ghr.nlm.nih.gov/condition/systemic-scleroderma

Clinical features

Calcinosis
MedGen UID:
709
Concept ID:
C0006663
Finding
Deposition of calcium in the tissues. It may be the result of a metabolic disorder or long-standing infection, or it may be associated with the presence of cancer.
Telangiectasia
MedGen UID:
21088
Concept ID:
C0039446
Disease or Syndrome
Local dilatation of small vessels resulting in red discoloration of the skin or mucous membranes.
Sclerodactyly
MedGen UID:
472893
Concept ID:
C0150988
Disease or Syndrome
Localized thickening and tightness of the skin of the fingers or toes.
Chromosome breakage
MedGen UID:
91280
Concept ID:
C0376628
Cell or Molecular Dysfunction
Elevated rate of chromosomal breakage or interchanges occurring either spontaneously or following exposure to various DNA-damaging agents. This feature may be assayed by treatment of cultured lymphocytes with agents such as chemical mutagens, irradiation, and alkylating agents.
Scleroderma
MedGen UID:
226896
Concept ID:
C1274865
Disease or Syndrome
A chronic autoimmune phenomenon characterized by fibrosis (or hardening) and vascular alterations of the skin.
Abnormality of chromosome stability
MedGen UID:
347878
Concept ID:
C1859424
Finding
A type of chromosomal aberration reduced resistance of chromosomes to change or deterioration.
Abnormality of abdomen morphology
MedGen UID:
866551
Concept ID:
C4020869
Anatomical Abnormality
A structural abnormality of the abdomen ('belly'), that is, the part of the body between the pelvis and the thorax.

Recent clinical studies

Etiology

Schwaiger JP, Khanna D, Gerry Coghlan J
Eur Respir Rev 2013 Dec;22(130):515-25. doi: 10.1183/09059180.00006013. PMID: 24293467
Chwieśko-Minarowska S, Kowal K, Bielecki M, Kowal-Bielecka O
Folia Histochem Cytobiol 2012 Jul 5;50(2):180-5. PMID: 22763975
Caramaschi P, Dalla Gassa A, Prati D, Barausse G, Tinazzi I, Ravagnani V, Confente S, Biasi D
Rheumatol Int 2012 Jul;32(7):1933-8. Epub 2011 Mar 30 doi: 10.1007/s00296-011-1878-y. PMID: 21448643
Zuhur F, Zuhur SS, Zuhur C, Musellim B, Ongen G
Rheumatol Int 2012 Jun;32(6):1655-61. Epub 2011 Mar 5 doi: 10.1007/s00296-011-1842-x. PMID: 21373783
Greger RE, Greger RE
Arch Dermatol 1975 Jan;111(1):81-5. PMID: 1119827

Diagnosis

Monteiro A, Mendes A, Silveira F, Castro L, Nadais G
Neurology 2014 Apr 15;82(15):e124-8. doi: 10.1212/WNL.0000000000000311. PMID: 24733862
Schwaiger JP, Khanna D, Gerry Coghlan J
Eur Respir Rev 2013 Dec;22(130):515-25. doi: 10.1183/09059180.00006013. PMID: 24293467
Caramaschi P, Dalla Gassa A, Prati D, Barausse G, Tinazzi I, Ravagnani V, Confente S, Biasi D
Rheumatol Int 2012 Jul;32(7):1933-8. Epub 2011 Mar 30 doi: 10.1007/s00296-011-1878-y. PMID: 21448643
Zuhur F, Zuhur SS, Zuhur C, Musellim B, Ongen G
Rheumatol Int 2012 Jun;32(6):1655-61. Epub 2011 Mar 5 doi: 10.1007/s00296-011-1842-x. PMID: 21373783
Melani L, Cardinali C, Giomi B, Schincaglia E, Caproni M, Fabbri P
Skinmed 2005 May-Jun;4(3):188-90. PMID: 15891259

Therapy

Kucukguven A, Khalil RA
Curr Drug Targets 2013 Mar;14(3):287-324. PMID: 23316963Free PMC Article
Johnson JN, Kvistad BS, Reed AM, Porter CB, O'Leary PW, Driscoll DJ
Congenit Heart Dis 2013 Jan-Feb;8(1):E1-4. Epub 2011 Jul 31 doi: 10.1111/j.1747-0803.2011.00554.x. PMID: 21801316
Caramaschi P, Dalla Gassa A, Prati D, Barausse G, Tinazzi I, Ravagnani V, Confente S, Biasi D
Rheumatol Int 2012 Jul;32(7):1933-8. Epub 2011 Mar 30 doi: 10.1007/s00296-011-1878-y. PMID: 21448643
Mould TL, Roberts-Thomson PJ
Asian Pac J Allergy Immunol 2000 Dec;18(4):195-200. PMID: 11316039
Rose T, Nothjunge J, Schlote W
Eur J Pediatr 1985 Jan;143(3):225-8. PMID: 3872796

Prognosis

Nakayama A, Tunnicliffe DJ, Thakkar V, Singh-Grewal D, O'Neill S, Craig JC, Tong A
J Rheumatol 2016 Jul;43(7):1363-75. Epub 2016 May 1 doi: 10.3899/jrheum.151309. PMID: 27134259
Schwaiger JP, Khanna D, Gerry Coghlan J
Eur Respir Rev 2013 Dec;22(130):515-25. doi: 10.1183/09059180.00006013. PMID: 24293467
Stock CJ, Sato H, Fonseca C, Banya WA, Molyneaux PL, Adamali H, Russell AM, Denton CP, Abraham DJ, Hansell DM, Nicholson AG, Maher TM, Wells AU, Lindahl GE, Renzoni EA
Thorax 2013 May;68(5):436-41. Epub 2013 Jan 15 doi: 10.1136/thoraxjnl-2012-201786. PMID: 23321605
Caramaschi P, Dalla Gassa A, Prati D, Barausse G, Tinazzi I, Ravagnani V, Confente S, Biasi D
Rheumatol Int 2012 Jul;32(7):1933-8. Epub 2011 Mar 30 doi: 10.1007/s00296-011-1878-y. PMID: 21448643
Zuhur F, Zuhur SS, Zuhur C, Musellim B, Ongen G
Rheumatol Int 2012 Jun;32(6):1655-61. Epub 2011 Mar 5 doi: 10.1007/s00296-011-1842-x. PMID: 21373783

Clinical prediction guides

Ichimura Y, Asano Y, Akamata K, Aozasa N, Noda S, Taniguchi T, Takahashi T, Toyama T, Sumida H, Kuwano Y, Yanaba K, Tada Y, Sugaya M, Sato S, Kadono T
Acta Derm Venereol 2014 Mar;94(2):157-62. doi: 10.2340/00015555-1680. PMID: 23995677
Schwaiger JP, Khanna D, Gerry Coghlan J
Eur Respir Rev 2013 Dec;22(130):515-25. doi: 10.1183/09059180.00006013. PMID: 24293467
Caramaschi P, Dalla Gassa A, Prati D, Barausse G, Tinazzi I, Ravagnani V, Confente S, Biasi D
Rheumatol Int 2012 Jul;32(7):1933-8. Epub 2011 Mar 30 doi: 10.1007/s00296-011-1878-y. PMID: 21448643
Zuhur F, Zuhur SS, Zuhur C, Musellim B, Ongen G
Rheumatol Int 2012 Jun;32(6):1655-61. Epub 2011 Mar 5 doi: 10.1007/s00296-011-1842-x. PMID: 21373783
Mould TL, Roberts-Thomson PJ
Asian Pac J Allergy Immunol 2000 Dec;18(4):195-200. PMID: 11316039

Recent systematic reviews

Nakayama A, Tunnicliffe DJ, Thakkar V, Singh-Grewal D, O'Neill S, Craig JC, Tong A
J Rheumatol 2016 Jul;43(7):1363-75. Epub 2016 May 1 doi: 10.3899/jrheum.151309. PMID: 27134259
Yang X, Mardekian J, Sanders KN, Mychaskiw MA, Thomas J 3rd
Clin Rheumatol 2013 Oct;32(10):1519-31. Epub 2013 Jun 20 doi: 10.1007/s10067-013-2307-2. PMID: 23780636Free PMC Article

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