The majority of haematological malignancies represent sporadic diseases, but hereditary
entities with predisposing genetic alterations have also been described. Diseases
of the myeloid and lymphoid cell lineages with genetic predispositions are associated
with heterogeneous clinical manifestations, with many symptoms being specific for
certain cytogenetic and molecular aberrations. Apart from the myeloid predisposition
syndromes with clear Mendelian inheritance patterns, cases with ambiguous predisposing
factors are also known, but their role in hereditary leukemogenesis is still poorly
understood. The presence of these genetic lesions is usually associated with an increased
risk of familial malignancies and often leads to familial disease aggregation. Lymphoid
malignancies often lack the disease-associated germline pathogenic variants, with
their propensity to familial aggregation being most likely explained by their complex
genotype serving as a hereditary base to many sporadic diseases. The heterogeneous
clinical features and the large number of potentially affected genes tend to make
the diagnosis of hereditary haematological malignancies difficult, however the elevated
familial risk caused by predisposing genetic alterations underlines the importance
of testing for individuals and families with genetic susceptibility.
