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Dyskeratosis congenita, autosomal recessive 8(DKCB8)

MedGen UID:
1824030
Concept ID:
C5774257
Disease or Syndrome
Synonym: DKCB8
 
Gene (location): DCLRE1B (1p13.2)
 
Monarch Initiative: MONDO:0859319
OMIM®: 620133

Definition

Autosomal recessive dyskeratosis congenita-8 (DKCB8) is characterized by progressive bone marrow failure affecting all lineages apparent from infancy or early childhood. More variable features may include poor growth, mild developmental delay, immunodeficiency, and gastrointestinal manifestations, such as esophageal stricture or inflammatory bowel disease. Some patients may have mucocutaneous features, including oral leukoplakia, nail dystrophy, or pigmentary skin abnormalities, although these features may be absent. Unlike patients with other forms of DKC, those with DKCB8 do not have shortened telomeres, although there is evidence of telomere instability. Hematopoietic stem cell transplant may be curative (Kermasson et al., 2022). For a discussion of genetic heterogeneity of dyskeratosis congenita, see DKCA1 (127550). [from OMIM]

Clinical features

From HPO
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Inflammation of the large intestine
MedGen UID:
662273
Concept ID:
C0578878
Disease or Syndrome
Inflammation, or an inflammatory state in the large intestine.
Pancolitis
MedGen UID:
1720692
Concept ID:
C0868908
Disease or Syndrome
Inflammation of the entire colon.
Esophageal stricture
MedGen UID:
1637009
Concept ID:
C4551650
Disease or Syndrome
A pathological narrowing of the esophagus that is caused by the development of a ring of scar tissue that constricts the esophageal lumen.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
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.
Immunodeficiency
MedGen UID:
7034
Concept ID:
C0021051
Disease or Syndrome
Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance.
B lymphocytopenia
MedGen UID:
340780
Concept ID:
C1855067
Finding
An abnormal decrease from the normal count of B cells.
Reduced natural killer cell count
MedGen UID:
383765
Concept ID:
C1855767
Finding
Less than normal number of natural killer cells, a type of lymphocyte in the innate immune system with an ability to mediate cytotoxicity and produce cytokines after the ligation of a germline-encoded activation receptor.
Oral mucosa leukoplakia
MedGen UID:
9738
Concept ID:
C0023532
Neoplastic Process
A thickened white patch on the oral mucosa that cannot be rubbed off.
Sparse scalp hair
MedGen UID:
346499
Concept ID:
C1857042
Finding
Decreased number of hairs per unit area of skin of the scalp.
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.
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.
Premature birth
MedGen UID:
57721
Concept ID:
C0151526
Pathologic Function
The birth of a baby of less than 37 weeks of gestational age.
Hypotelorism
MedGen UID:
96107
Concept ID:
C0424711
Finding
Interpupillary distance less than 2 SD below the mean (alternatively, the appearance of an decreased interpupillary distance or closely spaced eyes).
Chromosomal breakage induced by crosslinking agents
MedGen UID:
867372
Concept ID:
C4021737
Finding
Increased amount of chromosomal breaks in cultured blood lymphocytes or other cells induced by treatment with DNA cross-linking agents such as diepoxybutane and mitomycin C.

Recent clinical studies

Etiology

Vittal A, Niewisch MR, Bhala S, Kudaravalli P, Rahman F, Hercun J, Kleiner DE, Savage SA, Koh C, Heller T, Giri N
Hepatology 2023 Dec 1;78(6):1777-1787. Epub 2023 May 16 doi: 10.1097/HEP.0000000000000461. PMID: 37184208Free PMC Article
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

Diagnosis

Tummala H, Walne A, Buccafusca R, Alnajar J, Szabo A, Robinson P, McConkie-Rosell A, Wilson M, Crowley S, Kinsler V, Ewins AM, Madapura PM, Patel M, Pontikos N, Codd V, Vulliamy T, Dokal I
Am J Hum Genet 2022 Aug 4;109(8):1472-1483. doi: 10.1016/j.ajhg.2022.06.014. PMID: 35931051Free PMC Article
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
Ratnasamy V, Navaneethakrishnan S, Sirisena ND, Grüning NM, Brandau O, Thirunavukarasu K, Dagnall CL, McReynolds LJ, Savage SA, Dissanayake VHW
BMC Med Genet 2018 May 25;19(1):85. doi: 10.1186/s12881-018-0584-y. PMID: 29801475Free PMC Article
Ballew BJ, Joseph V, De S, Sarek G, Vannier JB, Stracker T, Schrader KA, Small TN, O'Reilly R, Manschreck C, Harlan Fleischut MM, Zhang L, Sullivan J, Stratton K, Yeager M, Jacobs K, Giri N, Alter BP, Boland J, Burdett L, Offit K, Boulton SJ, Savage SA, Petrini JH
PLoS Genet 2013 Aug;9(8):e1003695. Epub 2013 Aug 29 doi: 10.1371/journal.pgen.1003695. PMID: 24009516Free PMC Article
Baran I, Nalcaci R, Kocak M
Int J Dent Hyg 2010 Feb;8(1):68-74. doi: 10.1111/j.1601-5037.2009.00364.x. PMID: 20096085

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

Vittal A, Niewisch MR, Bhala S, Kudaravalli P, Rahman F, Hercun J, Kleiner DE, Savage SA, Koh C, Heller T, Giri N
Hepatology 2023 Dec 1;78(6):1777-1787. Epub 2023 May 16 doi: 10.1097/HEP.0000000000000461. PMID: 37184208Free PMC Article
Handley TP, Ogden GR
J Oral Pathol Med 2006 Sep;35(8):508-12. doi: 10.1111/j.1600-0714.2006.00434.x. PMID: 16918603

Clinical prediction guides

Vittal A, Niewisch MR, Bhala S, Kudaravalli P, Rahman F, Hercun J, Kleiner DE, Savage SA, Koh C, Heller T, Giri N
Hepatology 2023 Dec 1;78(6):1777-1787. Epub 2023 May 16 doi: 10.1097/HEP.0000000000000461. PMID: 37184208Free PMC Article
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

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