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Thrombocytopenia 1(XLT; THC1)

MedGen UID:
326416
Concept ID:
C1839163
Disease or Syndrome
Synonyms: Thrombocytopenia, X-linked; THROMBOCYTOPENIA, X-LINKED, 1; X-linked thrombocytopenia with normal platelets
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Gene (location): WAS (Xp11.23)
 
Monarch Initiative: MONDO:0010743
OMIM®: 313900
Orphanet: ORPHA852

Disease characteristics

Excerpted from the GeneReview: WAS-Related Disorders
The WAS-related disorders, which include Wiskott-Aldrich syndrome, X-linked thrombocytopenia (XLT), and X-linked congenital neutropenia (XLN), are a spectrum of disorders of hematopoietic cells, with predominant defects of platelets and lymphocytes caused by pathogenic variants in WAS. WAS-related disorders usually present in infancy. Affected males have thrombocytopenia with intermittent mucosal bleeding, bloody diarrhea, and intermittent or chronic petechiae and purpura; eczema; and recurrent bacterial and viral infections, particularly of the ear. At least 40% of those who survive the early complications develop one or more autoimmune conditions including hemolytic anemia, immune thrombocytopenic purpura, immune-mediated neutropenia, rheumatoid arthritis, vasculitis, and immune-mediated damage to the kidneys and liver. Individuals with a WAS-related disorder, particularly those who have been exposed to Epstein-Barr virus (EBV), are at increased risk of developing lymphomas, which often occur in unusual, extranodal locations including the brain, lung, or gastrointestinal tract. Males with XLT have thrombocytopenia with small platelets; other complications of Wiskott-Aldrich syndrome, including eczema and immune dysfunction, are usually mild or absent. Males with XLN have congenital neutropenia, myeloid dysplasia, and lymphoid cell abnormalities. [from GeneReviews]
Authors:
Sharat Chandra  |  Lucas Bronicki  |  Chinmayee B Nagaraj, et. al.   view full author information

Additional descriptions

From OMIM
Hereditary nonsyndromic thrombocytopenia is characterized by decreased numbers of platelets and bleeding tendency (summary by Villa et al., 1995). Genetic Heterogeneity of Hereditary Thrombocytopenia Autosomal dominant forms of thrombocytopenia include THC2 (188000), caused by mutation in the ANKRD26 (610855) gene on chromosome 10p12; THC4 (612004), caused by mutation in the CYCS gene (123970) on chromosome 7p15; THC5 (616216), caused by mutation in the ETV6 gene (600618) on chromosome 12p13; THC6 (616937), caused by mutation in the SRC gene (190090) on chromosome 20q11; THC7 (619130), caused by mutation in the IKZF5 gene (606238) on chromosome 10q26; THC8 (620475), caused by mutation in the ACTB gene (102630) on chromosome 7p22; THC9 (620478), caused by mutation in the THPO gene (600044) on chromosome 3q27; and THC11 (620654), caused by mutation in the RAP1B gene (179530) on chromosome 12q14. Autosomal recessive forms include THC3 (273900), caused by mutation in the FYB gene (602731) on chromosome 5p13; THC10 (620484), caused by mutation in the PTPRJ gene (600925) on chromosome 11p11; THC12 (620757), caused by mutation in the GNE gene (603824) on chromosome 9p13; and THC13 (620776), caused by mutation in the GALE gene (606953) on chromosome 1p36.  http://www.omim.org/entry/313900
From MedlinePlus Genetics
X-linked thrombocytopenia is a bleeding disorder that primarily affects males. This condition is characterized by a blood cell abnormality called thrombocytopenia, which is a shortage in the number of blood cells involved in clotting (platelets). Affected individuals often have abnormally small platelets as well, a condition called microthrombocytopenia. X-linked thrombocytopenia can cause individuals to bruise easily or have episodes of prolonged bleeding following minor trauma or even in the absence of injury (spontaneous bleeding). Some people with this condition experience spontaneous bleeding in the brain (cerebral hemorrhage), which can cause brain damage that can be life-threatening.

Some people with X-linked thrombocytopenia also have patches of red, irritated skin (eczema) or an increased susceptibility to infections. In severe cases, additional features can develop, such as cancer or autoimmune disorders, which occur when the immune system malfunctions and attacks the body's own tissues and organs. It is unclear, however, if people with these features have X-linked thrombocytopenia or a more severe disorder with similar signs and symptoms called Wiskott-Aldrich syndrome.

Some people have a mild form of the disorder called intermittent thrombocytopenia. These individuals have normal platelet production at times with episodes of thrombocytopenia.  https://medlineplus.gov/genetics/condition/x-linked-thrombocytopenia

Clinical features

From HPO
Joint hemorrhage
MedGen UID:
5479
Concept ID:
C0018924
Pathologic Function
Hemorrhage occurring within a joint.
Epistaxis
MedGen UID:
4996
Concept ID:
C0014591
Pathologic Function
Epistaxis, or nosebleed, refers to a hemorrhage localized in the nose.
Congenital thrombocytopenia
MedGen UID:
124422
Concept ID:
C0272278
Disease or Syndrome
Thrombocytopenia with congenital onset.
Decreased mean platelet volume
MedGen UID:
853132
Concept ID:
C1096368
Finding
Average platelet volume below the lower limit of the normal reference interval.
Intermittent thrombocytopenia
MedGen UID:
374151
Concept ID:
C1839167
Finding
Reduced platelet count that occurs sporadically, i.e., it comes and goes.
Abnormality of the musculature
MedGen UID:
867380
Concept ID:
C4021745
Anatomical Abnormality
Abnormality originating in one or more muscles, i.e., of the set of muscles of body.
Eczematoid dermatitis
MedGen UID:
3968
Concept ID:
C0013595
Disease or Syndrome
Eczema is a form of dermatitis that is characterized by scaly, pruritic, erythematous lesions located on flexural surfaces.
Increased circulating IgE level
MedGen UID:
116018
Concept ID:
C0236175
Finding
An abnormally increased overall level of immunoglobulin E in blood.
Increased circulating IgA level
MedGen UID:
66800
Concept ID:
C0239984
Finding
An abnormally increased level of immunoglobulin A in blood.
Petechiae
MedGen UID:
10680
Concept ID:
C0031256
Disease or Syndrome
Petechiae are pinpoint-sized reddish/purple spots, resembling a rash, that appear just under the skin or a mucous membrane when capillaries have ruptured and some superficial bleeding into the skin has happened. This term refers to an abnormally increased susceptibility to developing petechiae.
Bruising susceptibility
MedGen UID:
140849
Concept ID:
C0423798
Finding
An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVThrombocytopenia 1
Follow this link to review classifications for Thrombocytopenia 1 in Orphanet.

Professional guidelines

PubMed

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J Thromb Haemost 2013 Jan;11(1):56-70. doi: 10.1111/jth.12070. PMID: 23217107

Recent clinical studies

Etiology

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Diagnosis

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Therapy

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Prognosis

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Arthritis Rheum 2013 Sep;65(9):2450-6. doi: 10.1002/art.38052. PMID: 23780828
Warkentin TE
Semin Hematol 1998 Oct;35(4 Suppl 5):9-16; discussion 35-6. PMID: 9855179

Clinical prediction guides

Bitetti I, Lanzara V, Margiotta G, Varone A
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Semin Hematol 1998 Oct;35(4 Suppl 5):9-16; discussion 35-6. PMID: 9855179

Recent systematic reviews

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