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Dyskeratosis congenita, autosomal recessive 3(DKCB3)

MedGen UID:
462792
Concept ID:
C3151442
Disease or Syndrome
Synonyms: DKCB3; DYSKERATOSIS CONGENITA, AUTOSOMAL RECESSIVE 3
 
Gene (location): WRAP53 (17p13.1)
 
Monarch Initiative: MONDO:0013520
OMIM®: 613988

Disease characteristics

Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD 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  |  Marena R Niewisch   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

From HPO
Squamous cell carcinoma of the tongue
MedGen UID:
91153
Concept ID:
C0349566
Neoplastic Process
A carcinoma derived from a squamous epithelial cell of the tongue.
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 relative to marrow fat.
Oral mucosa leukoplakia
MedGen UID:
9738
Concept ID:
C0023532
Neoplastic Process
A thickened white patch on the oral mucosa that cannot be rubbed off.
Nail dystrophy
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 of the pigmentation of the skin.
Short telomere length
MedGen UID:
1627435
Concept ID:
C4531138
Anatomical Abnormality
An abnormal reduction in telomere length. Telomeres are non-coding, repetitive sequences of DNA at the ends of the chromosomes of eukaryotic cells which become shorter as cells divide, and when telomere attrition reaches its limit, cell proliferation arrest, senescence, and apoptosis can occur.

Recent clinical studies

Etiology

Niewisch MR, Giri N, McReynolds LJ, Alsaggaf R, Bhala S, Alter BP, Savage SA
Blood 2022 Mar 24;139(12):1807-1819. doi: 10.1182/blood.2021013523. PMID: 34852175Free PMC Article
Khincha PP, Savage SA
Semin Fetal Neonatal Med 2016 Feb;21(1):57-65. Epub 2015 Dec 24 doi: 10.1016/j.siny.2015.12.003. PMID: 26724991Free PMC Article
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. 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. PMID: 23453664Free PMC Article

Diagnosis

Niewisch MR, Giri N, McReynolds LJ, Alsaggaf R, Bhala S, Alter BP, Savage SA
Blood 2022 Mar 24;139(12):1807-1819. doi: 10.1182/blood.2021013523. PMID: 34852175Free PMC Article
Khincha PP, Savage SA
Semin Fetal Neonatal Med 2016 Feb;21(1):57-65. Epub 2015 Dec 24 doi: 10.1016/j.siny.2015.12.003. PMID: 26724991Free PMC Article
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. 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. PMID: 22899009Free PMC Article
Marrone A, Mason PJ
Cell Mol Life Sci 2003 Mar;60(3):507-17. doi: 10.1007/s000180300042. PMID: 12737310Free PMC Article

Therapy

Niewisch MR, Giri N, McReynolds LJ, Alsaggaf R, Bhala S, Alter BP, Savage SA
Blood 2022 Mar 24;139(12):1807-1819. doi: 10.1182/blood.2021013523. PMID: 34852175Free PMC Article

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. PMID: 22899009Free PMC Article
Marrone A, Mason PJ
Cell Mol Life Sci 2003 Mar;60(3):507-17. doi: 10.1007/s000180300042. PMID: 12737310Free PMC Article
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

Niewisch MR, Giri N, McReynolds LJ, Alsaggaf R, Bhala S, Alter BP, Savage SA
Blood 2022 Mar 24;139(12):1807-1819. doi: 10.1182/blood.2021013523. PMID: 34852175Free 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. PMID: 22899009Free PMC Article
Marrone A, Mason PJ
Cell Mol Life Sci 2003 Mar;60(3):507-17. doi: 10.1007/s000180300042. PMID: 12737310Free PMC Article

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