Dyskeratosis Congenita Workup

Updated: Jan 27, 2020
  • Author: David T Robles, MD, PhD, FAAD; Chief Editor: William D James, MD  more...
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Workup

Laboratory Studies

Perform appropriate tests to screen for bone marrow failure, pulmonary disease, neurologic disease, and mucosal malignancies. Specific tests depend on the clinical findings and may include a CBC count, chest radiography, pulmonary function tests, and stool tests for occult blood. Elevated von Willebrand factor levels have been associated with fatal vascular complications after bone marrow transplantation and may be a marker for patients with a predisposition for endothelial deterioration.

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Imaging Studies

Several reports note that radiographs show calcification of the basal ganglia.

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Dermoscopic Findings

The dermatoscope is another useful tool used to examine cutaneous findings associated with dyskeratosis congenita (DKC). The image seen is typically described as pigmented lines made up of brown dots and globules arranged in a netlike pattern. [56]

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Genetic Testing

Mutational analysis may be useful in confirming the diagnosis. Mutations in the TERC gene and in the TERT gene, the gene for telomerase reverse transcriptase (another member of the ribonucleoprotein complex), have been identified in a subset of patients with aplastic anemia. [57] Genetic testing for occult dyskeratosis congenita (DKC) should be considered in patients with aplastic anemia. However, a 2006 genetic analysis of the TERC gene among 284 children with either aplastic anemia or myelodysplastic syndrome found only 2 mutations in the TERC gene. [58]

Patients and family members without a known mutation can be screened with a new test, leukocyte subset flow fluorescence in situ hybridization, which can identify very short telomeres in both clinically apparent and silent disease. [59]

The flow-FISH (fluorescent in situ hybridization) technique is also a cost-effective method that can also be used to measure telomere length. [60]

One study found significant overlap in symptomatology between dyskeratosis congenita (DKC) and four other genetic syndromes (causative genes in parentheses): poikiloderma with neutropenia (USB1), Dubowitz syndrome (LIG4), and ectodermal dysplasia/short stature syndrome (GRHL2). [55] Patients with these disorders may present with somatic features resembling DKC, which may confound diagnosis and subsequently delay management. [55] Therefore, genetic testing for USB1, LIG4, and GRHL2 is suggested in addition to the conventional DKC workup. [55]

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Histologic Findings

Skin biopsy specimens from the areas of reticulated pigmentation typically show nonspecific changes, including mild hyperkeratosis, epidermal atrophy, telangiectasia of the superficial blood vessels, and melanophages in the papillary dermis. Interface changes have also been reported, with mild basal layer vacuolization and a lymphocytic inflammatory infiltrate in the upper dermis.

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