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Dyskeratosis congenita

MedGen UID:
78580
Concept ID:
C0265965
Disease or Syndrome
Synonym: Dyskeratosis Congenita
SNOMED CT: DKC - Dyskeratosis congenita (74911008); Cole-Engmann-Zinsser syndrome (74911008); Zinsser-Cole-Engmann syndrome (74911008); Dyskeratosis congenita (74911008); Zinsser-Cole-Engman syndrome (74911008); Congenital dyskeratosis (74911008)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: 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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: 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.
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.
 
Related genes: NHP2, NOP10, WRAP53, RTEL1, TINF2, TERT, TERC, PARN, DKC1
 
Monarch Initiative: MONDO:0015780
OMIM® Phenotypic series: PS127550
Orphanet: ORPHA1775

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 MedlinePlus Genetics
Dyskeratosis congenita is a disorder that can affect many parts of the body. There are three features that are characteristic of this disorder: fingernails and toenails that grow poorly or are abnormally shaped (nail dystrophy); changes in skin coloring (pigmentation), especially on the neck and chest, in a pattern often described as "lacy"; and white patches inside the mouth (oral leukoplakia).

People with dyskeratosis congenita have an increased risk of developing several life-threatening conditions. They are especially vulnerable to disorders that impair bone marrow function. These disorders disrupt the ability of the bone marrow to produce new blood cells. Affected individuals may develop aplastic anemia, also known as bone marrow failure, which occurs when the bone marrow does not produce enough new blood cells. They are also at higher than average risk for myelodysplastic syndrome, a condition in which immature blood cells fail to develop normally; this condition may progress to a form of blood cancer called leukemia. People with dyskeratosis congenita are also at increased risk of developing leukemia even if they never develop myelodysplastic syndrome. In addition, they have a higher than average risk of developing other cancers, especially cancers of the head, neck, anus, or genitals.

People with dyskeratosis congenita may also develop pulmonary fibrosis, a condition that causes scar tissue (fibrosis) to build up in the lungs, decreasing the transport of oxygen into the bloodstream. Additional signs and symptoms that occur in some people with dyskeratosis congenita include eye abnormalities such as narrow tear ducts that may become blocked, preventing drainage of tears and leading to eyelid irritation; dental problems; hair loss or prematurely grey hair; low bone mineral density (osteoporosis); degeneration (avascular necrosis) of the hip and shoulder joints; or liver disease. Some affected males may have narrowing (stenosis) of the urethra, which is the tube that carries urine out of the body from the bladder. Urethral stenosis may lead to difficult or painful urination and urinary tract infections.

The severity of dyskeratosis congenita varies widely among affected individuals. The least severely affected individuals have only a few mild physical features of the disorder and normal bone marrow function. More severely affected individuals have many of the characteristic physical features and experience bone marrow failure, cancer, or pulmonary fibrosis by early adulthood.

While most people with dyskeratosis congenita have normal intelligence and development of motor skills such as standing and walking, developmental delay may occur in some severely affected individuals. In one severe form of the disorder called Hoyeraal Hreidaarsson syndrome, affected individuals have an unusually small and underdeveloped cerebellum, which is the part of the brain that coordinates movement. Another severe variant called Revesz syndrome involves abnormalities in the light-sensitive tissue at the back of the eye (retina) in addition to the other symptoms of dyskeratosis congenita.  https://medlineplus.gov/genetics/condition/dyskeratosis-congenita

Professional guidelines

PubMed

Tummala H, Walne A, Dokal I
Expert Rev Hematol 2022 Aug;15(8):685-696. Epub 2022 Aug 8 doi: 10.1080/17474086.2022.2108784. PMID: 35929966
Vieri M, Brümmendorf TH, Beier F
Best Pract Res Clin Haematol 2021 Jun;34(2):101282. Epub 2021 Jul 1 doi: 10.1016/j.beha.2021.101282. PMID: 34404536
Niewisch MR, Savage SA
Expert Rev Hematol 2019 Dec;12(12):1037-1052. Epub 2019 Sep 10 doi: 10.1080/17474086.2019.1662720. PMID: 31478401Free PMC Article

Suggested Reading

Recent clinical studies

Etiology

Savage SA
Hematology Am Soc Hematol Educ Program 2022 Dec 9;2022(1):637-648. doi: 10.1182/hematology.2022000394. PMID: 36485133Free PMC Article
Warnakulasuriya S, Kujan O, Aguirre-Urizar JM, Bagan JV, González-Moles MÁ, Kerr AR, Lodi G, Mello FW, Monteiro L, Ogden GR, Sloan P, Johnson NW
Oral Dis 2021 Nov;27(8):1862-1880. Epub 2020 Nov 26 doi: 10.1111/odi.13704. PMID: 33128420
AlSabbagh MM
J Dtsch Dermatol Ges 2020 Sep;18(9):943-967. Epub 2020 Sep 15 doi: 10.1111/ddg.14268. PMID: 32930426
Niewisch MR, Savage SA
Expert Rev Hematol 2019 Dec;12(12):1037-1052. Epub 2019 Sep 10 doi: 10.1080/17474086.2019.1662720. PMID: 31478401Free PMC Article
Warnakulasuriya S
Oral Surg Oral Med Oral Pathol Oral Radiol 2018 Jun;125(6):582-590. Epub 2018 Apr 4 doi: 10.1016/j.oooo.2018.03.011. PMID: 29673799

Diagnosis

Warnakulasuriya S, Kujan O, Aguirre-Urizar JM, Bagan JV, González-Moles MÁ, Kerr AR, Lodi G, Mello FW, Monteiro L, Ogden GR, Sloan P, Johnson NW
Oral Dis 2021 Nov;27(8):1862-1880. Epub 2020 Nov 26 doi: 10.1111/odi.13704. PMID: 33128420
AlSabbagh MM
J Dtsch Dermatol Ges 2020 Sep;18(9):943-967. Epub 2020 Sep 15 doi: 10.1111/ddg.14268. PMID: 32930426
Niewisch MR, Savage SA
Expert Rev Hematol 2019 Dec;12(12):1037-1052. Epub 2019 Sep 10 doi: 10.1080/17474086.2019.1662720. PMID: 31478401Free PMC Article
Warnakulasuriya S
Oral Surg Oral Med Oral Pathol Oral Radiol 2018 Jun;125(6):582-590. Epub 2018 Apr 4 doi: 10.1016/j.oooo.2018.03.011. PMID: 29673799
Lu W, Zhang Y, Liu D, Songyang Z, Wan M
Exp Cell Res 2013 Jan 15;319(2):133-41. Epub 2012 Sep 21 doi: 10.1016/j.yexcr.2012.09.005. PMID: 23006819Free PMC Article

Therapy

Stoopler ET, Shanti RM
Mayo Clin Proc 2019 Sep;94(9):1668-1669. doi: 10.1016/j.mayocp.2019.04.032. PMID: 31486376
Warnakulasuriya S
Oral Surg Oral Med Oral Pathol Oral Radiol 2018 Jun;125(6):582-590. Epub 2018 Apr 4 doi: 10.1016/j.oooo.2018.03.011. PMID: 29673799
Gupta V, Kumar A
Adv Exp Med Biol 2010;685:215-9. doi: 10.1007/978-1-4419-6448-9_20. PMID: 20687509
Dokal I
Hematol J 2003;4(1):3-9. doi: 10.1038/sj.thj.6200215. PMID: 12692514
Schnur RE, Heymann WR
Semin Cutan Med Surg 1997 Mar;16(1):72-80. doi: 10.1016/s1085-5629(97)80038-7. PMID: 9125768

Prognosis

Rayinda T, van Steensel M, Danarti R
Int J Dermatol 2021 Nov;60(11):1343-1353. Epub 2021 Mar 19 doi: 10.1111/ijd.15498. PMID: 33739439
Karremann M, Neumaier-Probst E, Schlichtenbrede F, Beier F, Brümmendorf TH, Cremer FW, Bader P, Dürken M
Orphanet J Rare Dis 2020 Oct 23;15(1):299. doi: 10.1186/s13023-020-01553-y. PMID: 33097095Free PMC Article
Stoopler ET, Shanti RM
Mayo Clin Proc 2019 Sep;94(9):1668-1669. doi: 10.1016/j.mayocp.2019.04.032. PMID: 31486376
Warnakulasuriya S
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Angrisani A, Vicidomini R, Turano M, Furia M
Biol Chem 2014 Jun;395(6):593-610. doi: 10.1515/hsz-2013-0287. PMID: 24468621

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
Vieri M, Brümmendorf TH, Beier F
Best Pract Res Clin Haematol 2021 Jun;34(2):101282. Epub 2021 Jul 1 doi: 10.1016/j.beha.2021.101282. PMID: 34404536
Martínez P, Blasco MA
J Cell Biol 2017 Apr 3;216(4):875-887. Epub 2017 Mar 2 doi: 10.1083/jcb.201610111. PMID: 28254828Free PMC Article
Vulliamy T, Dokal I
Semin Hematol 2006 Jul;43(3):157-66. doi: 10.1053/j.seminhematol.2006.04.001. PMID: 16822458
Marrone A, Mason PJ
Cell Mol Life Sci 2003 Mar;60(3):507-17. doi: 10.1007/s000180300042. PMID: 12737310

Recent systematic reviews

Liu AQ, Deane EC, Prisman E, Durham JS
Ann Otol Rhinol Laryngol 2022 Sep;131(9):1036-1042. Epub 2021 Oct 15 doi: 10.1177/00034894211047470. PMID: 34651516Free PMC Article
Wang P, Xu Z
BMC Pulm Med 2021 Sep 3;21(1):279. doi: 10.1186/s12890-021-01645-w. PMID: 34479523Free PMC Article
Elmahadi S, Muramatsu H, Kojima S
Curr Opin Hematol 2016 Nov;23(6):501-507. doi: 10.1097/MOH.0000000000000290. PMID: 27607446
Barbaro P, Vedi A
Biol Blood Marrow Transplant 2016 Jul;22(7):1152-1158. Epub 2016 Mar 8 doi: 10.1016/j.bbmt.2016.03.001. PMID: 26968789

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