Until the beginning of the 20th century, it was believed that the genetic information was fully determined at the time of fertilization; the discovery of Mendel's laws in 1865 and that of the chromosome theory in 1891, showed that there was a genetic variation in the subsequent generations.[@bb0060]^,^[@bb0075]
The most reliable way of establishing kinship is to analyze the mtDNA genome.[@bb0080]^,^[@bb0085] The second generation of familial studies refers to the testing of the first degree relatives of the patient and may include the analysis of the patient and their relatives.[@bb0090]
Diseases with an autosomal inheritance pattern may be diagnosed using a detailed clinical history, an analysis of first degree relatives and the molecular studies of genes related to the disease. The significance of family history has been well established in the diagnosis and management of a variety of disorders. The study of the disease in several family members may allow us to predict the type of mutation, the age of onset and the risk of recurrence in future family members.[@bb0095]^,^[@bb0100]
The risk of the disease may be estimated based on the pattern of inheritance, the disease prevalence and the age of the patient. The risk may be either low or high.[@bb0105] The prediction of the risk may be based on clinical and molecular criteria such as age, severity of the phenotype, the results of molecular studies and the relationship between the patient and the relatives.[@bb0110]^,^[@bb0115]
The risk of disease recurrence is based on the molecular analysis of the relatives. In the analysis of the parents, the risk of recurrence is high and in the analysis of the offspring it is estimated as 50%.[@bb0120] The risk of recurrence may be higher in relatives of the patient with the disease as well as in those with a positive family history.[@bb0125]
The recurrence risk is estimated to be low in the relatives of patients with certain diseases such as childhood cancer or neurodevelopmental conditions.[@bb0115]^,^[@bb0130]
Regarding the newborns with a positive family history, there is a risk of recurrence up to 70%.[@bb0135] The recurrence risk increases when the affected relative is a parent or when the inheritance is dominant.[@bb
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