ABSTRACT
Continued monitoring of a family for new malignant tumors has revealed diverse immunological and neoplastic disorders during a 15-year period. In 1966, the proband developed lymphoma. In 1975, his antibody titers to Epstein-Barr virus (EBV) became elevated, and again, he developed a malignant lymphoma. He also had borderline hypo-immunoglobulin A, died of glioblastoma multiforme in 1977, and at autopsy, had adenomatous colonic polyps. His eldest brother has normal immunoglobulin levels, but developed immune thrombocytopenia in 1973 and had elevated EBV antibody titers in 1980. Another brother had hypo-immunoglobulin A, thymoma in 1965, and adenomas and adenocarcinoma of the colon. Two other brothers succumbed to glioblastoma in 1968 and 1969. The father of the proband had bronchiectasis in 1952, hypo-immunoglobulin M documented in 1972, and elevated EBV antibody titers 5 years preceding development of a malignant lymphoma. The latter contained 10 EBV genome equivalents/cell by EBV viral DNA/DNA reassociation kinetics analysis. The proband's grandmother had died of an immunoglobulin G-secreting myeloma in 1977, and his grandfather had borderline low immunoglobulin M, elevated EBV antibody titers, and hypopharyngeal carcinoma in 1980. Predisposition to oncogenesis in this family was probably inherited.
Subject(s)
Antibodies, Viral/analysis , Herpesvirus 4, Human/immunology , IgA Deficiency , Neoplasms/genetics , Adenocarcinoma/genetics , Adenoma/genetics , Adolescent , Adult , Animals , Child , Female , Glioblastoma/genetics , Glioblastoma/microbiology , Humans , Lymphoma/genetics , Male , Middle Aged , Neoplasms/microbiology , Pedigree , Recurrence , Thymoma/genetics , Tumor Virus Infections/immunologySubject(s)
Lymphoproliferative Disorders/diagnosis , Lymphoproliferative Disorders/etiology , Sex Chromosomes , X Chromosome , Adolescent , Adult , Aging , Burkitt Lymphoma/diagnosis , Child , Child, Preschool , Diagnosis, Differential , Dose-Response Relationship, Immunologic , Female , HLA Antigens/genetics , Humans , Immunologic Deficiency Syndromes/diagnosis , Infectious Mononucleosis/genetics , Infectious Mononucleosis/therapy , Leukemia, Lymphoid/drug therapy , Lymphoproliferative Disorders/genetics , Male , Pedigree , Phenotype , Prognosis , SyndromeABSTRACT
Investigation of a family with cancer in boys revealed that at least 20 males had the X-linked recessive lymphoproliferative syndrome. A variety of phenotypes occurred: aproliferative phenotypes consisted of aplastic anemia, agranulocytosis or acquired hypogammaglobulinemia; and proliferative phenotypes of B cells included disorders associated with the Epstein-Barr virus, American Burkitt's lymphoma, immunoblastic sarcoma of B cells, fatal infectious mononucleosis or plasmacytoma. The lymphoproliferative disorders observed in males could have resulted from an immunodeficiency to Epstein-Barr virus. The variable phenotypic expression could have resulted from individual differences in the viral dose, duration of exposure and age at which the boys were exposed to the virus. Aproliferative phenotypes such as acquired hypogammaglobulinemia could have ensued from excessive suppressor-cell activity on B cells, whereas proliferative phenotypes such as Burkitt's lymphoma or fatal infectious mononucleosis could have resulted from infection by Epstein-Barr virus and failure to stop proliferation of B cells.
Subject(s)
Hematologic Diseases/genetics , Immunologic Deficiency Syndromes/genetics , Lymphoma/genetics , Sex Chromosomes , X Chromosome , Adolescent , B-Lymphocytes/immunology , Burkitt Lymphoma/genetics , Child , Child, Preschool , Female , Genes, Recessive , Genetic Linkage , Hematologic Diseases/immunology , Herpesvirus 4, Human/immunology , Humans , Infant , Infant, Newborn , Infectious Mononucleosis/genetics , Lymphoma/immunology , Male , PedigreeABSTRACT
Five brothers of from 6 to 18 years of age experienced immunological or neoplastic disorders during an 8-year interval. 2 boys succumbed to glioblastoma multiforme, another to metastatic carcinoma, and the 2 surviving brothers had a histiocytic lymphoma and idiopathic thrombocytopenia purpura, respectively. The mother of the boys was healthy, but her twin sister died in utero of birth defects. We suggest that an intrinsic cellular defect inherited from their mother rendered the boys vulnerable to oncogenesis.
Subject(s)
Neoplasms/genetics , Purpura, Thrombocytopenic/genetics , Adolescent , Carcinoma/genetics , Child , Glioblastoma/genetics , Humans , Lymphoma/genetics , Male , Neoplasm Metastasis , PedigreeABSTRACT
Subtle immunodeficiency to infectious agents including measles virus and ten Epstein-Barr virus (EBV) has been described in the X-linked recessive lymphoproliferative syndrome. This syndrome has affected six male cousins and possibly another boy. Three brothers died of an infectious mononucleosis syndrome, in a maternal cousin agammaglobulinemia developed three years after infectious mononucleosis, and two half-brothers of the Duncan kindred died of lymphoma of the brain and intestinal tract, respectively. In three of the boys, unusual measles viral infections had developed. Paramyxovirus-like particles suggestive of measles virus were seen at necropsy in the atrophic lymphoid tissue of two boys. Also, numerous plasma cells were seen in the brains, visceral organs and the thymus glands, and thymic-dependent lymphocytes were sparse in lymph nodes and spleen. The abnormal lymphopoiesis in the syndrome probably results from a subtle immunodeficiency, and concurrent measles and EB virus infections.
