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Year : 2020  |  Volume : 8  |  Issue : 4  |  Page : 206-208

A petit telomere – A catalyst for bone marrow failure

Department of General Medicine, Victoria Hospital, Bangalore Medical College and Research Institute, Bengaluru, Karnataka, India

Date of Submission22-Mar-2020
Date of Decision24-Apr-2020
Date of Acceptance06-Jun-2020
Date of Web Publication23-Oct-2020

Correspondence Address:
Dr. G Madhu
S/O Gangadharachar, C/O Mahesh Building, City Co Operative Society Road Corner, Hosaline Road, Hassan - 573 201, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/AJIM.AJIM_56_19

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Dyskeratosis congenita (DC) is a rare inherited disorder estimated to affect 1 in 1 million people characterized by rapidly depleting telomere length causing premature apoptosis or senescence results in progressive bone marrow failure. It is also known as Zinsser–Engman–Cole syndrome, and it was first described in 1906. The classic triads of DC include reticulated skin hyperpigmentation, nail dystrophy, and oral leukoplakia. Here, we report a case of a 20-year-old female presented with anemia symptoms and, on evaluation, diagnosed as bone marrow failure secondary to DC.

Keywords: Dyskeratosis congenita, inherited bone marrow failure syndrome, short telomere syndrome

How to cite this article:
Nirmala A C, Madhu G. A petit telomere – A catalyst for bone marrow failure. APIK J Int Med 2020;8:206-8

How to cite this URL:
Nirmala A C, Madhu G. A petit telomere – A catalyst for bone marrow failure. APIK J Int Med [serial online] 2020 [cited 2021 Mar 2];8:206-8. Available from: https://www.ajim.in/text.asp?2020/8/4/206/298938

  Introduction Top

Dyskeratosis congenita (DC) is a prototypic short telomere syndrome[1] characterized by bone marrow failure, cancer predisposition, and additional somatic abnormalities. Other short telomere syndromes are aplastic anemia, ataxia telangiectasia, and Fanconi anemia. DC and related telomere syndromes are caused by mutations that interfere with normal maintenance of telomeres, the regions at the ends of the chromosomes which protect nucleated cells from the loss or gain of genetic materials.

At birth, the length of telomeric DNA from somatic cells such as lymphocytes ranges from 8 to 14 kilobases (kb).[2] With each cell division, 50–100 base pairs of this telomeric DNA is removed due to incomplete replication of the 3' ends. When telomeres reach a critically short threshold, the cell can no longer divide properly and undergoes apoptosis or senescence.[3] In most somatic cells, shortening of telomere length is a normal consequence of aging.

Compared with the normal rate of telomere shortening in unaffected individuals of approximately 60 bp/year, individuals with telomere disorders lose telomeric DNA at approximately 120 bp/year.[4] Furthermore, successive generations of affected individuals may be born with progressively shorter telomeres (a phenomenon known as disease anticipation).[5] Premature telomere shortening leads to premature cell death, senescence, or genomic instability, which in turn leads to impaired organ and tissue function, altered homeostasis, or inappropriate growth.[6]

To date, there are 14 genes that have been identified with DKC (ACD, DKC1, TERC, TERT, NOP10, NHP2, TINF2, USB1, TCAB1, CTC1, PARN, RTEL1, WRAP53, and C16orf57).[7] All genes associated with this syndrome encode proteins in the telomerase complex responsible for maintaining telomeres at the ends of chromosomes regarding shortening length, protection, and replication.[8] The most common mode of inheritance is an X-linked recessive form which affects DKC1 gene (located at Xq28), which encodes for the protein dyskerin. It is also inherited by autosomal dominant and autosomal recessive pattern.

  Case Report Top

A 20-year-old female presented with a history of easy fatiguability for 1 month, nobleeding manifestation, or recurrent infections. She received multiple blood transfusions since the age of 8 years. There was no significant family history.

On examination, severe pallor, short stature [Figure 1] and dental caries are present, reticlar hyperpigmentation noted all over the body sparing the face[ [Figure 2] but no nail changes are noted, other findings include hyperpigmentation of dorsum of the tongue, hyperhidrosis, polydactyly thumb on the right hand. Another systemic examination is normal.
Figure 1: Short stature of the patient noticed here

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Figure 2: Reticular hyperpigmentation noted all over the both forearms

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On investigation, complete blood count shows hemoglobin of 5.6 g%, white blood cell: 3510 cells/cumm with normal differential, and platelets: 75,000 and corrected reticulocyte count is 0.8%. Peripheral smear shows macrocytic anemia with neutropenia and thrombocytopenia. Vitamin B12 and Iron profile was normal. Bone marrow aspiration and biopsy showed hypocellular marrow with a cell:fat ratio of 20:80 [Figure 3] and dyserythropoiesis. Skin biopsy showed atrophic epidermis and significant melanophages in the upper dermis consistent with DC. Other investigations such as renal function test, liver function test, thyroid profile, and hemoglobin electrophoresis were normal. Ultrasound sonography (USG) abdomen was normal. Mutation analysis was not done due to financial constraints.
Figure 3: Bone marrow aspiration and biopsy showing hypocellular marrow

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  Discussion Top

DC can affect the bone marrow, immune system, skin, lung, liver, and teeth. Patients are also at increased risk of a number of malignancies, most commonly head/neck squamous cell carcinoma followed by stomach/esophageal cancer. These features can be variable and include the classic presentations of DC or other variants and atypical presentations in which only a subset of findings are present. The mucocutaneous features of DKC typically develop between ages 5 and 15 years. The median age of the onset of peripheral cytopenia is 10 years.

The minimum requirement to diagnose DKS is the presence of 2 of 4 major features of the mucocutaneous features, bone marrow failure, and 2 or more of the other somatic symptoms. In the present case, the mucocutaneous features are reticular skin and hyperhidrosis, and somatic symptoms are short stature and dental caries.

There is no specific treatment for DC. Bone marrow failure can be treated with anabolic steroids (e.g., oxymetholone), granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, and erythropoietin,[9] but the long-term, curative option is hematopoietic stem cell transplantation (SCT). However, the success rate of SCT is limited because of a high prevalence of fatal pulmonary complications, which likely reflect preexisting pulmonary disease in these patients.[10]

Early diagnosis of DC helps in surveillance of patients for additional clinical manifestations including cancer and organ dysfunction and also helps to identify family members who shared the same mutation but not showing classical clinical features due to less penetrance of the disease.

The overall survival of individuals with DC has been reported around 50 years. The primary cause of mortality in individuals with DC and related telomere disorders is bone marrow failure, its consequences (e.g., bleeding and infection), or morbidity associated with its treatment using HCT.[6] Solid tumors, pulmonary fibrosis, and hepatic disease account for significant mortality as well.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Barbaro PM, Ziegler DS, Reddel RR. The wide-ranging clinical implications of the short telomere syndromes. Intern Med J 2016;46:393-403.  Back to cited text no. 1
Aubert G, Baerlocher GM, Vulto I, Poon SS, Lansdorp PM. Collapse of telomere homeostasis in hematopoietic cells caused by heterozygous mutations in telomerase genes. PLoS Genet 2012;8:e1002696.  Back to cited text no. 2
Alter BP, Baerlocher GM, Savage SA, Chanock SJ, Weksler BB, Willner JP, et al . Very short telomere length by flow fluorescence in situ hybridization identifies patients with dyskeratosis congenita. Blood 2007;110:1439-47.  Back to cited text no. 3
Townsley DM, Dumitriu B, Liu D, Biancotto A, Weinstein B, Chen C, et al . Danazol treatment for telomere diseases. N Engl J Med 2016;374:1922-31.  Back to cited text no. 4
Vulliamy T, Marrone A, Szydlo R, Walne A, Mason PJ, Dokal I. Disease anticipation is associated with progressive telomere shortening in families with dyskeratosis congenita due to mutations in TERC. Nat Genet 2004;36:447-9.  Back to cited text no. 5
Dokal I. Dyskeratosis congenita. Hematology Am Soc Hematol Educ Program 2011;2011:480-6.  Back to cited text no. 6
Islam A, Rafiq S, Kirwan M, Walne A, Cavenagh J, Vulliamy T, et al . Haematological recovery in dyskeratosis congenita patients treated with danazol. Br J Haematol 2013;162:854-6.  Back to cited text no. 7
Touzot F, Le Guen T, de Villartay JP, Revy P. Dyskeratosis congenita: Short telomeres are not the rule. Med Sci (Paris) 2012;28:618-24.  Back to cited text no. 8
Brault ME, Lauzon C, Autexier C. Dyskeratosis congenita mutations in dyskerin SUMOylation consensus sites lead to impaired telomerase RNA accumulation and telomere defects. Hum Mol Genet 2013;22:3498-507.  Back to cited text no. 9
Gadalla SM, Sales-Bonfim C, Carreras J, Alter BP, Antin JH, Ayas M, et al . Outcomes of allogeneic hematopoietic cell transplantation in patients with dyskeratosis congenita. Biol Blood Marrow Transplant 2013;19:1238-43.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3]


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