Autopsy and Case Reports
https://autopsyandcasereports.org/article/doi/10.4322/acr.2020.203
Autopsy and Case Reports
Autopsy Case Report

Dyskeratosis congenita

Lorenzo Gitto; Robert Stoppacher; Timothy Eric Richardson; Serenella Serinelli

http://dx.doi.org/10.4322/acr.2020.203 Autops Case Rep, vol.10, n3, e2020203, 2020
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Abstract

Dyskeratosis congenita (DC) is a genetic syndrome with progressive multisystem involvement classically characterized by the clinical triad of oral leukoplakia, nail dystrophy, and reticular hyperpigmentation. Frequent complications are bone marrow failure, increased rate of malignancy, lung and liver diseases. DC results from an anomalous progressive shortening of telomeres resulting in DNA replication problems inducing replicative senescence. We report a death due to DC in a 16-year-old male with bone marrow failure and multiple organ dysfunction. At autopsy, nail dystrophy and skin hypopigmentation were observed. Gross and microscopic examinations of the internal organs showed cardiac hypertrophy, multiple lung consolidations and prominent interstitial fibrosis, liver cirrhosis, and fibrosis. Multiple foci of extramedullary hematopoiesis were identified, including on the epidural surface of the dura, that is an infrequent location, mimicking a focal area of epidural hemorrhage. Only a few autopsy studies about DC are reported in the literature. Further research should be done to understand the pathophysiology of the disease and its complications.

Keywords

Autopsy, Dyskeratosis Congenita, Hematopoiesis, Extramedullary, Pathology, Telomere Shortening

References

Zinsser F. Atrophia cutis reticularis cum pigmentione, dystrophia unguium et leukoplakia oris.

Ikonogr Dermatol (Hyoto). 1906;5:219-23.

Engmann MF. A unique case of reticular pigmentation of the skin with atrophy.

Arch Dermatol Syph. 1926;13:685-7.

Cole HN, Rauschkolb JC, Toomey J. Dyskeratosis congenita with pigmentation, dystrophia unguis and leukokeratosis oris.

Arch Dermatol Syph. 1930;21(1):71-95. [https://doi.org/10.1001/archderm.1930.01440070079008].

Savage SA, Alter BP. Dyskeratosis congenita.

Hematol Oncol Clin North Am. 2009;23(2):215-31. [https://doi.org/10.1016/j.hoc.2009.01.003]. [PMID:19327580]

Nelson ND, Bertuch AA. Dyskeratosis congenita as a disorder of telomere maintenance.

Mutat Res. 2012;730(1-2):43-51. [https://doi.org/10.1016/j.mrfmmm.2011.06.008]. [PMID:21745483]

Okuda K, Bardeguez A, Gardner JP, et al. Telomere length in the newborn.

Pediatr Res. 2002;52(3):377-81. [https://doi.org/10.1203/00006450-200209000-00012]. [PMID:12193671]

Arai Y, Martin-Ruiz CM, Takayama M, et al. Inflammation, but not telomere length, predicts successful ageing at extreme old age: a longitudinal study of semi-supercentenarians.

EBioMedicine. 2015;2(10):1549-58. [https://doi.org/10.1016/j.ebiom.2015.07.029]. [PMID:26629551]

Lu W, Zhang Y, Liu D, Songyang Z, Wan M. Telomeres-structure, function, and regulation.

Exp Cell Res. 2013;319(2):133-41. [https://doi.org/10.1016/j.yexcr.2012.09.005]. [PMID:23006819]

Savage SA, Giri N, Baerlocher GM, Orr N, Lansdorp PM, Alter BP. TINF2, a component of the shelterin telomere protection complex, is mutated in dyskeratosis congenita.

Am J Hum Genet. 2008;82(2):501-9. [https://doi.org/10.1016/j.ajhg.2007.10.004]. [PMID:18252230]

Yang D, He Q, Kim H, Ma W, Songyang Z. TIN2 protein dyskeratosis congenita missense mutants are defective in association with telomerase.

J Biol Chem. 2011;286(26):23022-30. [https://doi.org/10.1074/jbc.M111.225870]. [PMID:21536674]

Rogers M. Nail manifestations of some important genetic disorders in children.

Dermatol Ther. 2002;15(2):111-20. [https://doi.org/10.1046/j.1529-8019.2002.01515.x].

Ward SC, Savage SA, Giri N, Alter BP, Cowen EW. Progressive reticulate skin pigmentation and anonychia in a patient with bone marrow failure.

J Am Acad Dermatol. 2017;77(6):1194-8. [https://doi.org/10.1016/j.jaad.2017.07.018]. [PMID:29033247]

Atkinson JC, Harvey KE, Domingo DL, et al. Oral and dental phenotype of dyskeratosis congenita.

Oral Dis. 2008;14(5):419-27. [https://doi.org/10.1111/j.1601-0825.2007.01394.x]. [PMID:18938267]

Vulliamy T, Dokal I. Dyskeratosis congenita.

Semin Hematol. 2006;43(3):157-66. [https://doi.org/10.1053/j.seminhematol.2006.04.001]. [PMID:16822458]

Iraji F, Jamshidi K, Pourazizi M, Abtahi-Naeini B. Dyskeratosis congenita without oral involvement: a rare hereditary disease.

Oman Med J. 2015;30(3):212-5. [https://doi.org/10.5001/omj.2015.44]. [PMID:26171129]

Alter BP, Giri N, Savage SA, Rosenberg PS. Cancer in dyskeratosis congenita.

Blood. 2009;113(26):6549-57. [https://doi.org/10.1182/blood-2008-12-192880]. [PMID:19282459]

Lee CM, Salzman KL, Blumenthal DT, Gaffney DK. Intracranial extramedullary hematopoiesis: brief review of response to radiation therapy.

Am J Hematol. 2005;78(2):151-2. [https://doi.org/10.1002/ajh.20177]. [PMID:15682407]

Fukuhara A, Tanino Y, Ishii T, et al. Pulmonary fibrosis in dyskeratosis congenita with TINF2 gene mutation.

Eur Respir J. 2013;42(6):1757-9. [https://doi.org/10.1183/09031936.00149113]. [PMID:24072216]

Hoffman TW, van der Vis JJ, van Oosterhout MF, et al. TINF2 Gene Mutation in a Patient with Pulmonary Fibrosis.

Case Rep Pulmonol. 2016;2016:1310862. [https://doi.org/10.1155/2016/1310862]. [PMID:27088026]

Mahansaria SS, Kumar S, Bharathy KG, Kumar S, Pamecha V. Liver transplantation after bone marrow transplantation for end stage liver disease with severe hepatopulmonary syndrome in Dyskeratosis Congenita: a literature first.

J Clin Exp Hepatol. 2015;5(4):344-7. [https://doi.org/10.1016/j.jceh.2015.10.003]. [PMID:26900277]

Singh A, Pandey VK, Tandon M, Pandey CK. Dyskeratosis congenita induced cirrhosis for liver transplantation-perioperative management.

Indian J Anaesth. 2015;59(5):312-4. [https://doi.org/10.4103/0019-5049.156888]. [PMID:26019357]

Bryan HG, Nixon RK. Dyskeratosis congeniatand familial pancytopenia.

JAMA. 1965;192(3):203-20. [https://doi.org/10.1001/jama.1965.03080160023005]. [PMID:14270277]

Trowbridge AA, Sirinavin C, Linman JW. Dyskeratosis congenita: hematologic evaluation of a sibship and review of the literature.

Am J Hematogy. 1977;l3:143-152.

Mills SE, Coope PH, Beacham BE, Greet KE. Intracranial calcifications and dyskeratosis congenita.

Arch Dermatol. 1979;115(12):1437-143. [https://doi.org/10.1001/archderm.1979.04010120035015]. [PMID:533291]

Wiedemann HP, McGuire J, Dwyer JM, et al. Progressive immune failure in dyskeratosis congenita; report of an adult in whom Pneumocystitis carinii and fatal disseminated candidiasis developed.

Arch Intern Med. 1984;144(2):397-39. [https://doi.org/10.1001/archinte.1984.00350140227031]. [PMID:6607716]

Kawaguchi K, Sakamaki H, Onozawa Y, Koike M. Dyskeratosis congenita (Zinsser-Cole-Engman syndrome). An autopsy case presenting with rectal carcinoma, non-cirrhotic portal hypertension, and Pneumocystis carinii pneumonia.

Virchows Arch A Pathol Anat Histopathol. 1990;417(3):247-53. [https://doi.org/10.1007/BF01600141]. [PMID:2166977]

Verra F, Kouzan S, Saiag P, Bignon J, de Cremoux H. Bronchoalveolar disease in dyskeratosis congenita.

Eur Respir J. 1992;5(4):497-9. [PMID:1563509]

Rocha V, Devergie A, Socié G, et al. Unusual complications after bone marrow transplantation for dyskeratosis congenita.

Br J Haematol. 1998;103(1):243-8. [https://doi.org/10.1046/j.1365-2141.1998.00949.x]. [PMID:9792316]

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Submitted date:
05/31/2020

Accepted date:
06/27/2020

Publication date:
09/02/2020

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