eMedicine Specialties > Dermatology > Pediatric Diseases

Dyskeratosis Congenita: Treatment & Medication

Author: David T Robles, MD, PhD, Resident Physician, Department of Internal Medicine, Division of Dermatology, University of Washington School of Medicine
Coauthor(s): Jonathan M Olson, BS, University of Washington School of Medicine; Edward F Chan, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Philip H Fleckman, MD, Professor, Department of Internal Medicine, Division of Dermatology, University of Washington
Contributor Information and Disclosures

Updated: Jan 28, 2008

Treatment

Medical Care

Short-term treatment options for bone marrow failure in patients with DKC include anabolic steroids (eg, oxymetholone), granulocyte macrophage colony-stimulating factor, granulocyte colony-stimulating factor, and erythropoietin13 ; however, the only long-term, curative option is hematopoietic stem cell transplantation (SCT).

  • Approximately 50% of patients experience a temporary increase in blood counts with androgen therapy; the duration of treatment is limited by adverse effects; in addition, reports have described splenic peliosis and rupture in patients treated concomitantly with androgens and granulocyte colony-stimulating factor.14
  • 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.
  • Drugs that cause pulmonary toxicity (eg, busulfan) and exposure to unnecessary radiation should be avoided in these patients.
  • Nonmyeloablative hematopoietic SCT conditioning regimens (ie, reduced-intensity conditioning) with fludarabine may offer better outcomes. A 2007 review showed a 22% mortality rate with reduced-intensity conditioning in DKC treatment versus a  71% mortality rate with traditional myeloablative regimens.15
  • The best candidates for transplantation may be patients with sibling donors and with no preexisting pulmonary disease.

The elucidation of the genetic basis of X-Iinked DKC enables prenatal testing and carrier detection. Early diagnosis of DKC through genetic analysis also may help identify patients for early harvest and storage of their bone marrow for use after anticipated marrow failure. In the future, patients with DKC may be candidates for hematopoietic gene therapy.

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Colony-stimulating factors

Used to stimulate bone marrow in patients with cytopenia of one or more cell lineage.


Erythropoietin (Epogen, Procrit)

Stimulates division and differentiation of erythroid progenitor cells.

Adult

50-100 U/kg IV/SC, 3 times/wk; dosing may vary

Pediatric

Not established

Documented hypersensitivity; uncontrolled hypertension

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in porphyria, hypertension, and history of seizures; decrease dose if hematocrit value increase exceeds 4 U in any 2-wk period


Filgrastim (Neupogen)

Activates and stimulates production, maturation, migration, and cytotoxicity of neutrophils.

Adult

5 mcg/kg/d SC; dosing may vary

Pediatric

Not established

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not use 12-24 h before or 24 h after administering cytotoxic chemotherapy because increases sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy

More on Dyskeratosis Congenita

Overview: Dyskeratosis Congenita
Differential Diagnoses & Workup: Dyskeratosis Congenita
Treatment & Medication: Dyskeratosis Congenita
Follow-up: Dyskeratosis Congenita
References
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References

  1. Bessler M, Du HY, Gu B, Mason PJ. Dysfunctional telomeres and dyskeratosis congenita. Haematologica. Aug 2007;92(8):1009-12. [Medline].

  2. Garcia CK, Wright WE, Shay JW. Human diseases of telomerase dysfunction: insights into tissue aging. Nucleic Acids Res. 2007;35(22):7406-16. [Medline].

  3. Mason PJ, Wilson DB, Bessler M. Dyskeratosis congenita -- a disease of dysfunctional telomere maintenance. Curr Mol Med. Mar 2005;5(2):159-70. [Medline].

  4. Walne AJ, Marrone A, Dokal I. Dyskeratosis congenita: a disorder of defective telomere maintenance?. Int J Hematol. Oct 2005;82(3):184-9. [Medline].

  5. Marrone A, Sokhal P, Walne A, Beswick R, Kirwan M, Killick S, et al. Functional characterization of novel telomerase RNA (TERC) mutations in patients with diverse clinical and pathological presentations. Haematologica. Aug 2007;92(8):1013-20. [Medline].

  6. Marrone A, Walne A, Tamary H, Masunari Y, Kirwan M, Beswick R, et al. Telomerase reverse-transcriptase homozygous mutations in autosomal recessive dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome. Blood. Dec 15 2007;110(13):4198-205. [Medline].

  7. Walne AJ, Vulliamy T, Marrone A, Beswick R, Kirwan M, Masunari Y, et al. Genetic heterogeneity in autosomal recessive dyskeratosis congenita with one subtype due to mutations in the telomerase-associated protein NOP10. Hum Mol Genet. Jul 1 2007;16(13):1619-29. [Medline].

  8. Ruggero D, Grisendi S, Piazza F, Rego E, Mari F, Rao PH. Dyskeratosis congenita and cancer in mice deficient in ribosomal RNA modification. Science. Jan 10 2003;299(5604):259-62. [Medline].

  9. Alawi F, Lee MN. DKC1 is a direct and conserved transcriptional target of c-MYC. Biochem Biophys Res Commun. Nov 3 2007;362(4):893-8. [Medline].

  10. Dokal I, Vulliamy T. Dyskeratosis congenita: its link to telomerase and aplastic anaemia. Blood Rev. Dec 2003;17(4):217-25. [Medline].

  11. Field JJ, Mason PJ, An P, Kasai Y, McLellan M, Jaeger S. Low frequency of telomerase RNA mutations among children with aplastic anemia or myelodysplastic syndrome. J Pediatr Hematol Oncol. Jul 2006;28(7):450-3. [Medline].

  12. 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. Sep 1 2007;110(5):1439-47. [Medline].

  13. Erduran E, Hacisalihoglu S, Ozoran Y. Treatment of dyskeratosis congenita with granulocyte-macrophage colony-stimulating factor and erythropoietin. J Pediatr Hematol Oncol. Apr 2003;25(4):333-5. [Medline].

  14. Giri N, Pitel PA, Green D, Alter BP. Splenic peliosis and rupture in patients with dyskeratosis congenita on androgens and granulocyte colony-stimulating factor. Br J Haematol. Sep 2007;138(6):815-7. [Medline].

  15. Ostronoff F, Ostronoff M, Calixto R, Florêncio R, Domingues MC, Souto Maior AP, et al. Fludarabine, cyclophosphamide, and antithymocyte globulin for a patient with dyskeratosis congenita and severe bone marrow failure. Biol Blood Marrow Transplant. Mar 2007;13(3):366-8. [Medline].

  16. Dokal I. Dyskeratosis congenita in all its forms. Br J Haematol. Sep 2000;110(4):768-79. [Medline].

  17. Holman JD, Dyer JA. Genodermatoses with malignant potential. Curr Opin Pediatr. Aug 2007;19(4):446-54. [Medline].

  18. Mitchell JR, Wood E, Collins K. A telomerase component is defective in the human disease dyskeratosis congenita. Nature. Dec 2 1999;402(6761):551-5. [Medline].

  19. Mochizuki Y, He J, Kulkarni S, Bessler M, Mason PJ. Mouse dyskerin mutations affect accumulation of telomerase RNA and small nucleolar RNA, telomerase activity, and ribosomal RNA processing. Proc Natl Acad Sci U S A. Jul 20 2004;101(29):10756-61. [Medline].

  20. Montanaro L, Tazzari PL, Derenzini M. Enhanced telomere shortening in transformed lymphoblasts from patients with X linked dyskeratosis. J Clin Pathol. Aug 2003;56(8):583-6. [Medline].

  21. Vulliamy TJ, Marrone A, Knight SW, Walne A, Mason PJ, Dokal I. Mutations in dyskeratosis congenita: their impact on telomere length and the diversity of clinical presentation. Blood. Apr 1 2006;107(7):2680-5. [Medline].

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Further Reading

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Keywords

Zinsser-Engman-Cole syndrome, DKC, Hoyeraal-Hreidarsson syndrome, bone marrow failure, congenital dyskeratosis, reticular skin hyperpigmentation, nail dystrophy, oral leukoplakia, pancytopenia, testicular atrophy

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Contributor Information and Disclosures

Author

David T Robles, MD, PhD, Resident Physician, Department of Internal Medicine, Division of Dermatology, University of Washington School of Medicine
David T Robles, MD, PhD is a member of the following medical societies: American Academy of Dermatology and Society for Advancement of Chicanos and Native Americans in Science
Disclosure: Nothing to disclose.

Coauthor(s)

Jonathan M Olson, BS, University of Washington School of Medicine
Disclosure: Nothing to disclose.

Edward F Chan, MD, Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania School of Medicine
Edward F Chan, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Philip H Fleckman, MD, Professor, Department of Internal Medicine, Division of Dermatology, University of Washington
Philip H Fleckman, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Society for Cell Biology, Phi Beta Kappa, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Medical Editor

Jean Paul Ortonne, MD, Chair, Department of Dermatology, Professor, Hospital L'Archet, Nice University, France
Jean Paul Ortonne, MD is a member of the following medical societies: American Academy of Dermatology and American Dermatological Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Richard P Vinson, MD, Assistant Clinical Professor, Department of Dermatology, Texas Tech University School of Medicine; Consulting Staff, Mountain View Dermatology, PA
Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Van Perry, MD, Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas Health Science Center
Van Perry, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Laser Medicine and Surgery
Disclosure: Nothing to disclose.

CME Editor

Glen H Crawford, MD, Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital
Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

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