What is the diagnostic workup for Dyskeratosis congenita?

Diagnostic Workup for Dyskeratosis Congenita

The definitive diagnosis of Dyskeratosis Congenita (DC) requires measurement of telomere length by flow cytometry with fluorescent in situ hybridization (FISH), showing telomeres less than the first percentile for age in white blood cells. 1, 2

Clinical Evaluation

• Assess for the classic clinical triad:

  • Nail dystrophy
  • Lacy/reticulated skin pigmentation
  • Oral leukoplakia (present in 65% of DC patients) 3

• Additional clinical features to evaluate:

  • Dental abnormalities (decreased root/crown ratio, mild taurodontism) 3
  • Signs of bone marrow failure (pallor, petechiae, bruising)
  • Pulmonary symptoms (shortness of breath, cough)
  • Liver abnormalities
  • Growth and developmental delays

Laboratory Testing

• Complete blood count (CBC) with differential
• Bone marrow aspirate and biopsy (establish baseline) 1
• Telomere length measurement via flow-FISH (diagnostic gold standard) 1, 2
• Genetic testing for known DC-associated genes:
  • X-linked: DKC1
  • Autosomal dominant: TERC, TERT, TINF2, RTEL1
  • Autosomal recessive: NOP10, NHP2, CTC1, PARN, WRAP53
  • Either AD or AR: ACD, RTEL1, TERT 1

Multisystem Evaluation

• Pulmonary function tests (baseline when patient is old enough to perform them) 1
• Liver function tests
• Endocrine evaluation for growth 1
• Dental examination (assess for caries, periodontitis, tooth abnormalities) 3
• Otolaryngology evaluation (assess for oral leukoplakia and head/neck cancer risk) 1
• Gynecologic examination for females 1

Cancer Screening

• Oral cavity examination:
  • Monthly self-examinations
  • Biannual dental examinations
  • Annual head and neck cancer evaluation by an otolaryngologist (beginning by age 16) 1, 2
• Annual gynecologic examination for women 1
• For patients on androgen therapy:
  • Biannual hepatic ultrasounds
  • Liver function tests every three months 1, 2

Immunologic Assessment

• Immunoglobulin levels (IgG, IgA, IgM)
• Lymphocyte subset analysis (T, B, NK cells)
• Lymphocyte proliferation assays 1

Pitfalls and Caveats

• DC may be misdiagnosed as idiopathic aplastic anemia or chronic graft-versus-host disease 4
• Genetic anticipation can occur in families with telomere gene variants, resulting in earlier disease onset in subsequent generations 2
• Oral leukoplakia in young non-smokers should raise suspicion for DC 3
• DC can present with bone marrow failure before the classic mucocutaneous triad appears 4, 5
• Malignant transformation of oral leukoplakia to squamous cell carcinoma can occur and requires vigilant monitoring 6

By following this comprehensive diagnostic workup, clinicians can accurately diagnose DC and implement appropriate surveillance and management strategies to improve patient outcomes and quality of life.