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Dyskeratosis congenita, autosomal recessive, 3(DKCB3)

MedGen UID:
462792
Concept ID:
C3151442
Disease or Syndrome
Synonyms: DKCB3; Dyskeratosis Congenita
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
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 homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
 
Gene (location): WRAP53 (17p13.1)
OMIM®: 613988

Disease characteristics

Excerpted from the GeneReview: Dyskeratosis Congenita
Dyskeratosis congenita (DC), a telomere biology disorder, is characterized by a classic triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia. The classic triad may not be present in all individuals. People with DC are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include: abnormal pigmentation changes not restricted to the upper chest and neck, eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), and dental abnormalities (caries, periodontal disease, taurodauntism). Although most persons with DC have normal psychomotor development and normal neurologic function, significant developmental delay is present in the two variants in which additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome). Onset and progression of manifestations of DC vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF. [from GeneReviews]
Authors:
Sharon A Savage   view full author information

Additional description

From OMIM
Dyskeratosis congenita is a genetic disorder of defective tissue maintenance, impaired stem cell function, and cancer predisposition caused by short telomeres resulting from a defect in telomerase. Clinical manifestations may be seen in the skin as leukoplakia, nail dystrophy, and reticular pigmentation, in the bone marrow as pancytopenia, and in the lung as pulmonary fibrosis, as well as in other tissues (summary by Zhong et al., 2011). For a discussion of genetic heterogeneity of dyskeratosis congenita, see DKCA1 (127550).  http://www.omim.org/entry/613988

Clinical features

Squamous cell carcinoma
MedGen UID:
2874
Concept ID:
C0007137
Neoplastic Process
The presence of squamous cell carcinoma of the skin.
Pancytopenia
MedGen UID:
18281
Concept ID:
C0030312
Disease or Syndrome
An abnormal reduction in numbers of all blood cell types (red blood cells, white blood cells, and platelets).
Bone marrow hypocellularity
MedGen UID:
383749
Concept ID:
C1855710
Finding
A reduced number of hematopoietic cells present in the bone marrow.
Squamous cell carcinoma
MedGen UID:
2874
Concept ID:
C0007137
Neoplastic Process
The presence of squamous cell carcinoma of the skin.
Dystrophia unguium
MedGen UID:
66368
Concept ID:
C0221260
Disease or Syndrome
Onychodystrophy (nail dystrophy) refers to nail changes apart from changes of the color (nail dyschromia) and involves partial or complete disruption of the various keratinous layers of the nail plate.
Abnormality of skin pigmentation
MedGen UID:
224697
Concept ID:
C1260926
Finding
An abnormality in the formation or distribution of pigment, especially in the skin.
Nail dysplasia
MedGen UID:
331737
Concept ID:
C1834405
Disease or Syndrome
The presence of developmental dysplasia of the nail.

Recent clinical studies

Etiology

Wilson DB, Link DC, Mason PJ, Bessler M
Ann Med 2014 Sep;46(6):353-63. Epub 2014 Jun 3 doi: 10.3109/07853890.2014.915579. [Epub ahead of print] PMID: 24888387Free PMC Article
Walne AJ, Vulliamy T, Kirwan M, Plagnol V, Dokal I
Am J Hum Genet 2013 Mar 7;92(3):448-53. Epub 2013 Feb 28 doi: 10.1016/j.ajhg.2013.02.001. [Epub ahead of print] PMID: 23453664Free PMC Article

Diagnosis

Wilson DB, Link DC, Mason PJ, Bessler M
Ann Med 2014 Sep;46(6):353-63. Epub 2014 Jun 3 doi: 10.3109/07853890.2014.915579. [Epub ahead of print] PMID: 24888387Free PMC Article
Mroczek S, Krwawicz J, Kutner J, Lazniewski M, Kuciński I, Ginalski K, Dziembowski A
Genes Dev 2012 Sep 1;26(17):1911-25. Epub 2012 Aug 16 doi: 10.1101/gad.193169.112. [Epub ahead of print] PMID: 22899009Free PMC Article
Marrone A, Mason PJ
Cell Mol Life Sci 2003 Mar;60(3):507-17. PMID: 12737310

Prognosis

Mroczek S, Krwawicz J, Kutner J, Lazniewski M, Kuciński I, Ginalski K, Dziembowski A
Genes Dev 2012 Sep 1;26(17):1911-25. Epub 2012 Aug 16 doi: 10.1101/gad.193169.112. [Epub ahead of print] PMID: 22899009Free PMC Article
Marrone A, Mason PJ
Cell Mol Life Sci 2003 Mar;60(3):507-17. PMID: 12737310
Güngör T, Corbacioglu S, Storb R, Seger RA
Bone Marrow Transplant 2003 Mar;31(5):407-10. doi: 10.1038/sj.bmt.1703844. PMID: 12634734

Clinical prediction guides

Mroczek S, Krwawicz J, Kutner J, Lazniewski M, Kuciński I, Ginalski K, Dziembowski A
Genes Dev 2012 Sep 1;26(17):1911-25. Epub 2012 Aug 16 doi: 10.1101/gad.193169.112. [Epub ahead of print] PMID: 22899009Free PMC Article
Marrone A, Mason PJ
Cell Mol Life Sci 2003 Mar;60(3):507-17. PMID: 12737310

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