Late Presentation of Dyskeratosis Congenita: Germline Predisposition to Adult-Onset Secondary Acute Myeloid Leukemia

• Published in: Hematology reports 2022-12, Vol.14 (4), p.294-299
• Main Authors: Ramos, Harry, Aly, Mai Mostafa, Balasubramanian, Suresh Kumar
• Format: Article
• Language: English
• Subjects: Acute myeloid leukemia; AML; Anemia; Biopsy; Blood platelets; Bone marrow; Case Report; Case reports; Chemotherapy; Chromosome 7; Chromosome deletion; Chromosomes; del 7; Dyskeratosis; dyskeratosis congenita; Dystrophy; Family medical history; Fibrosis; FLT3-TKD; Gene deletion; Genes; Genetic counseling; Genetic testing; Hereditary diseases; Hypoplasia; Hypoxia; Leukemia; Leukocytosis; Leukokeratosis; Liver; Lung diseases; Malignancy; Mechanical ventilation; Metaphase; Mutation; Myelodysplastic syndrome; Pancytopenia; Patients; Pigmentation; Pulmonary fibrosis; Respiratory failure; Skin pigmentation; Telomerase; telomere; Yeast
• ISSN: 2038-8330; 2038-8322; 2038-8330
• DOI: 10.3390/hematolrep14040042

Classic dyskeratosis congenita is a hereditary disease where the majority of patients present with bone marrow failure and mucocutaneous changes: mainly skin pigmentation, nail dystrophy, oral premalignant leukoplakia, in addition to increased risk for malignancies. A 63-year-old man with a long history of untreated chronic pulmonary disease, a smoker in the past, presented initially with pancytopenia and a clinical diagnosis of myelodysplastic syndrome with excess blasts returned a month later with leukocytosis (WBC 215.9 × 106/μL) and diagnosed with acute myeloid leukemia (AML) with deletion of chromosome 7 and FLT3-TKD mutation. The patient’s mother and sister died in their 6th decade from rapidly progressing fulminant pulmonary fibrosis. He had abnormal skin pigmentation and oral leukoplakia on presentation. He was induced with 7 + 3 chemotherapy and started on midostaurin but experienced prolonged cytopenias, complicated by hypoxic acute on chronic respiratory failure requiring intubation and mechanical ventilation. D + 28 and D + 36 bone marrow examination showed trilineage hypoplasia but no blasts, though the D + 28 bone marrow biopsy revealed one metaphase with del (7) that was cleared on D + 35. The constellation of clinical features and strong family history along with del 7 and FLT3-TKD AML with preceding MDS highly suggests a germline predisposition state dyskeratosis congenita. Germline predispositions are often underrecognized as delayed onset conditions leading to AML and may have treatment and preventative implications especially genetic counseling for blood-related family members.