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X-linked severe congenital neutropenia(SCNX)

MedGen UID:
335314
Concept ID:
C1845987
Disease or Syndrome
Synonym: SCNX
SNOMED CT: X-linked severe congenital neutropenia (718882006)
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:0010294
OMIM®: 300299
Orphanet: ORPHA86788

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 neutropenia (XLN), are a spectrum of disorders of hematopoietic cells, with predominant defects of platelets and lymphocytes. Wiskott-Aldrich syndrome usually presents in infancy. Affected males have thrombocytopenia with intermittent mucosal bleeding, bloody diarrhea, and intermittent or chronic petechiae and purpura; recurrent bacterial, viral, fungal, and/or opportunistic infections; and eczema. Approximately 25%-40% of those who survive the early complications develop one or more autoimmune conditions including hemolytic anemia, immune thrombocytopenic purpura, immune-mediated neutropenia, vasculitis, rheumatoid arthritis, 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 small platelet volume and thrombocytopenia. Severe disease-related events include severe bleeding episodes (14%), autoimmunity (12%), life-threatening infections (7%), and malignancy (5%). Males with XLN typically have congenital neutropenia associated with myelodysplasia, hyperactive neutrophils, increased myeloid cell apoptosis, and lymphoid cell abnormalities. [from GeneReviews]
Authors:
Sharat Chandra  |  Chinmayee B Nagaraj  |  Miao Sun, et. al.   view full author information

Clinical features

From HPO
Bone marrow arrest at the promyelocytic stage
MedGen UID:
1781449
Concept ID:
C5539718
Cell or Molecular Dysfunction
A type of bone marrow maturation arrest characterized by accumulation of neutrophil precursor cells in the bone marrow.
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.
Monocytopenia
MedGen UID:
507013
Concept ID:
C0427544
Finding
An decreased number of circulating monocytes.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
Decreased CD4:CD8 ratio
MedGen UID:
163125
Concept ID:
C0853905
Finding
An abnormal reduction of the relative proportion of CD4+ to CD8+ T cells.
Recurrent bacterial infections
MedGen UID:
334943
Concept ID:
C1844383
Finding
Increased susceptibility to bacterial infections, as manifested by recurrent episodes of bacterial infection.

Professional guidelines

PubMed

Uzel G, Holland SM
Curr Allergy Asthma Rep 2002 Sep;2(5):385-91. doi: 10.1007/s11882-002-0071-5. PMID: 12165204

Recent clinical studies

Etiology

Smith BN, Ancliff PJ, Pizzey A, Khwaja A, Linch DC, Gale RE
Br J Haematol 2009 Mar;144(5):762-70. Epub 2008 Nov 22 doi: 10.1111/j.1365-2141.2008.07493.x. PMID: 19036076

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