Imunologic, hematologic and oncologic diseases in Down’s syndrome

The high susceptibility to infections, malignancies, and autoimmune disorders of Down’s syndrome (DS) subjects is associated with immunodeficiency. The percentage of circulating T-lymphocytes is low from birth, and lymphocyte proliferative response to mitogens declines rapidly after the 1st decade of life. T-lymphocyte maturation is impaired in DS. The immunodeficiency in DS results from a defect of the epithelial cells of the thymus which fail to synthesize or secrete one or more hormones necessary for the differentiation of T-lymphocytes. The thymus is morphologically deranged while the serum levels of thymic hormones are low. Immunological evaluation in children with DS may show IgG2 deficiency, low lymphocytes CD4+ count or reduced NK cells function. Children with Down’s syndrome (DS) need special clinical management because of the higher risk of haematological and immunological diseases. An abnormal hematopoietic function is a well-known characteristic of DS. These children frequently develop two kinds of clonal megakaryocytosis such as transient myeloproliferative disease and acute megakaryoblastic leukaemia. The incidence of leukemia is higher in children with DS, estimates ranging from 14-30 times the incidence rate observed for normal children. The peak incidence is in the newborn period and again at 3-6 years. The majority of cases (20%) are acute megakaryoblastic leukemias and their incidence is approximately 400-500-fold higher in DS than in normal children. Transient myeloproliferative disease occurs almost only in infants with DS. This reaction is characterized by a high spontaneous remission rate. Incidence of acute lymphoblastic leukaemia is 6-10 fold higher in children with DS, but it is rare in adults after 30 years. The overall incidence of solid tumours in patients with DS is significantly lower than normal, indicating that trisomy 21 offers protection against the development of solid tumours in children and adults. The nature of susceptibility to leukaemia and resistance to solid tumours is unknown.