Dyskeratosis Congenita: Relationship to Fanconi’s Anemia

Abstract

Dyskeratosis congenita and Fanconi’s anemia share impressive features in common: primary refractory pancytopenia; bone marrow hyperplasia (curtailed phase) and megaloblastosis, eventuating in severe hypoplasia of the marrow; cutaneous melanotic dyschromia; lacrimal duct blockage and a host of other minor abnormalities, in addition to mental retardation and generalized impairment of growth. Evaluation of two brothers with dyskeratosis congenita, and review of previous reports, indicate the following to be more prominent in dyskeratosis congenita than in Fanconi’s anemia: cutaneous telangiectatic erythema and atrophy; exocrine, ungual, and dental dysplasias; mucosal leukoplakia, carcinomatosis, and stenosis; and esophageal diverticula. Prominent in Fanconi’s anemia but not dyskeratosis congenita are the renal and particular skeletal anomalies. Possible transition cases are discussed. The proband studied suffered from progressive refractory pancytopenia, fevers, abdominal pains, malabsorption syndrome, and finally subarachnoid hemorrhage. Cultured leukocytes had normal-appearing karyotypes. The proband’s brother had cutaneous alterations of dyskeratosis congenita, but a hemogram revealed only mild thrombocytopenia and macrocytosis. Both brothers had elevated levels of hemoglobin F, leukocyte alkaline phosphatase, serum IgG, and thyroglobulin antibody, and both had reduced levels of serum IgM and vitamin B12.

Dyskeratosis Congenita Associated with Elevated Fetal Hemoglobin, X‐Linked Ocular Albinism, and Juvenile‐Onset Diabetes Mellitus

“…Levels of HbF were elevated in 15 reported cases of dyskeratosis congenita (9-21). Of this group, all of the cases that were pedigrees in which patterns of inheritance could be determined demonstrated X-linked inheritance (10,12,13,16,17). The average HbF for 12 of these patients was 9.5% and the range was 3.0% to 29.6%.…”

Dyskeratosis Congenita: A Case Report

“…The mode of inheritance in our case was difficult to ascertain. The spectrum of clinical manifestations in females may either be partial or complete (4,5). Net-like hyperpigmentation of the skin closely simulating poikiloderma vasculare atrophicans is the cardinal feature of this mesoectodermal disorder (3,6).…”

“…Hematologic changes of varying severity, affecting half of the cases, usually appear in the second or third decade (9). These patients may succumb to general debilitation, severe pancytopenia with progressive bone marrow hypoplasia, opportunistic infections, lymphoreticular malignancies, carcinomatosis arising from primary sites or less often, cirrhosis (2,3,5,9).…”

Marrow Hypoplasia Associated with Congenital Neurologic Anomalies in Two Siblings

“…An additional variant described by Bloom et al (7) with congenital thrombocytopenia and delayed onset pancytopenia in two males had neither congenital anomalies nor chromosomal aberrations; however, these patients were reported prior to the routine use of more sophisticated cytogenetic culturing techniques that utilize diepoxybutane or alkylating agents such as Mitomycin C to induce chromosome breakage. Dyskeratosis congenita is another form of delayed onset pancytopenia that shares a number of clinical features with other familial hypoplastic anemias, but does not have the increased incidence of chromosomal anomalies, as reported by Steier et al (8) and Inoue et al (9).…”