Dyskeratosis Congenita

Individuals with dyskeratosis congenita (DC) most commonly present with abnormal skin pigmentation, nail dystrophy, bone marrow failure and oral leukoplakia. Other features that may present include: epiphora, developmental delay, pulmonary disease, short stature, poor dentition, esophageal stricture, premature hair loss and an increased risk for a variety of malignancies. Individuals typically present during early childhood, often with abnormal skin pigmentation and nail dystrophy as the first clinical signs. By age 30, most individuals with DC have signs of bone marrow failure. However, there is a large degree of disease heterogeneity and severity, especially for heterozygous mutations in the TERT gene. Some patients may initially be characterized as having constitutional or idiopathic aplastic anemia or myelodysplastic syndromes. In addition, mutations in the TERC and TERT genes have been identified in individuals with reported idiopathic pulmonary fibrosis.10 Hoyeraal-Hreidarsson (HH) and Revesz Syndromes are severe forms of DC. HH is characterized by microcephaly, growth and mental retardation, spastic paresis, ataxia and immunodeficiency. Individuals with Revesz syndrome present with bilateral retinal exudative retinopathy and intracranial calcifications, in addition to many of the common DC features. Genetic anticipation can also be observed, with children displaying clinical features at an earlier age and/or with a more severe presentation as compared to a parent harboring the same mutation. In all forms of DC, telomere protection or maintenance is defective.

Tests Available

Forms and Documents

Test Details

DKC1
  • 1. Confirmation of a clinical diagnosis.
  • 2. Carrier testing for family members of the affected patient
  • 3. Confirmation that a potential hematopoietic stem cell transplant donor is not affected
  • 4. Prenatal diagnosis in at-risk pregnancies
  • Capillary Sequencing

Ordering

108
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Buccal Swabs

Billing

81479x1
Yes
Yes
  • 284 Aplastic anemia and other bone marrow failure syndromes
* For price inquiries please email zebras@genedx.com

References

  1. Vulliamy TJ, et al, Mutations in dyskeratosis congenita, Blood 107:2680-2685, 2006
  2. Vulliamy TJ, et al, The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenital, 2001, Nature 413:432
  3. He J, et al, Targeted disruption of Dkc1, the gene mutated in X-linked dyskeratosis congenital causes embryonic lethality in mice. 2002, Oncogene 21:7740

Forms and Documents

Test Details

TERC
  • Confirmation of a clinical diagnosis.
  • Carrier testing for family members of the affected patient
  • Confirmation that a potential hematopoietic stem cell transplant donor is not affected
  • Prenatal diagnosis in at-risk pregnancies
  • Capillary Sequencing

Ordering

107
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Dried Blood Spots | Buccal Swabs

Billing

81479x1
Yes
Yes
  • 284 Aplastic anemia and other bone marrow failure syndromes
* For price inquiries please email zebras@genedx.com

References

  1. Vulliamy TJ, et al, Mutations in dyskeratosis congenita, Blood 107:2680-2685, 2006
  2. Vulliamy TJ, et al, The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenital, 2001, Nature 413:432
  3. He J, et al, Targeted disruption of Dkc1, the gene mutated in X-linked dyskeratosis congenital causes embryonic lethality in mice. 2002, Oncogene 21:7740
  4. Goldman F et al, The effect of TERC haploinsufficiency on the inheritance of telomere length, 2005, PNAS 102:17119

Forms and Documents

Test Details

TINF2
  • Confirmation of a clinical diagnosis.
  • Carrier testing for family members of the affected patient
  • Confirmation that a potential hematopoietic stem cell transplant donor is not affected
  • Prenatal diagnosis in at-risk pregnancies
  • Capillary Sequencing

Ordering

414
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Dried Blood Spots | Buccal Swabs

Billing

81479x1
No
Yes
  • 284 Aplastic anemia and other bone marrow failure syndromes
* For price inquiries please email zebras@genedx.com

References

  1. Walne AJ et al, TINF2 Mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosis congenita and related bone marrow failure syndromes. 2008, Blood 112:3594-3600
  2. Savage SA et al, TINF2, a Component of the Shelterin Telomere Protection Complex, Is Mutated in Dyskeratosis Congenita. 2008, The American Journal of Human Genetics 82:501-509

Forms and Documents

Test Details

TERT
  • Confirmation of a clinical diagnosis.
  • Carrier testing for family members of the affected patient
  • Confirmation that a potential hematopoietic stem cell transplant donor is not affected
  • Prenatal diagnosis in at-risk pregnancies
  • Capillary Sequencing

Ordering

682
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Buccal Swabs

Billing

81479x1
No
Yes
  • 284 Aplastic anemia and other bone marrow failure syndromes
* For price inquiries please email zebras@genedx.com

References

  1. Vulliamy TJ, et al, Mutations in dyskeratosis congenita, Blood 107:2680-2685, 2006.
  2. Vulliamy TJ, et al, The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenital, 2001, Nature 413:432.
  3. He J, et al, Targeted disruption of Dkc1, the gene mutated in X-linked dyskeratosis congenital causes embryonic lethality in mice. 2002, Oncogene 21:7740.
  4. Goldman F et al, The effect of TERC haploinsufficiency on the inheritance of telomere length, 2005, PNAS 102:17119.
  5. Walne AJ et al, TINF2 Mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosis congenita and related bone marrow failure syndromes. 2008, Blood 112:3594-3600.
  6. Savage SA et al, TINF2, a Component of the Shelterin Telomere Protection Complex, Is Mutated in Dyskeratosis Congenita. 2008, The American Journal of Human Genetics 82:501-509.
  7. Vulliamy et al., Differences in Disease Severity but Similar Telomere Lengths in Genetic Subgroups of Patients with Telomerase and Shelterin Mutations. 2011. PLoS One. 6(9) e24383.
  8. Walne et al., Advances in the understanding of dyskeratosis congenita. 2009. British Journal of Haematology. 145:164-172.
  9. Savage et al., (2010) The genetics and clinical manifestations of telomere biology disorders. Genet Med. 12(12):753-64.
  10. Armanios et al., (2007) Telomerase Mutations in Families with Idiopathic Pulmonary Fibrosis. N Engl j Med. 356:1317-1326.

Forms and Documents

Test Details

ACD, CTC1, DKC1, NHP2, NOP10, PARN, RTEL1, TERC, TERT, TINF2, USB1, WRAP53
  • Confirmation of a clinical diagnosis.
  • Carrier testing for family members of the affected patient
  • Confirmation that a potential hematopoietic stem cell transplant donor is not affected
  • Prenatal diagnosis in at-risk pregnancies
  • Next-Gen Sequencing
  • Deletion/Duplication Analysis

Ordering

TB47
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Buccal Swabs | Extracted DNA

Billing

81479x1
No
Yes
* For price inquiries please email zebras@genedx.com