When Bloom syndrome , which also referred to as congenital telangiectatic syndrome is known, is a very rare, inherited disease that the human geneticists in the group of so-called chromosome breakage syndrome is classified.
The transmission of this disease associated with mutations follows an autosomal - recessive inheritance . This form of inheritance can also be observed in other chromosome instability syndromes , such as ataxia telangiectatica ( Louis Bar syndrome ) or Fanconi anemia .
It is difficult to give an exact frequency, but it is known that it is slightly increased in a certain population group, the Ashkenazi Jews . A frequency of about 1: 48,000 and a proportion of about 0.5% heterozygotes for the blmAsh mutation are estimated here . However, due to the recessive inheritance pattern, there is almost no manifestation in heterozygosity.
Those affected often have facial features that are characteristic of this syndrome. a. with micrognathia , furthermore the following symptoms and abnormalities are described in the literature:
- proportioned short stature
- Telangiectasia of the skin
- Skull deformities
- high sensitivity to the sun with hyper- or hypopigmentation
- increased susceptibility to infection due to various immune defects
- increased rate of malignancies (e.g. leukemia )
Mutations in the BLM gene, which codes for the Bloom syndrome protein , a RecQ 3'-5'-helicase , an enzyme that monitors the integrity in the interphase of the cell cycle , have been identified as the cause of Bloom syndrome . Mutations in this area lead to errors in the replication or repair of the DNA. Recombination is also influenced in this way. This manifests itself in an increased rate of sister chromatid (abbreviated to SCE for sister chromatid exchanges ), which can be made visible by specific techniques. The SCEs represent a kind of "mitotic crossing over", i.e. an exchange of chromosome fragments among the individual sister chromatids. In some cases, more than 50 SCE can be observed simultaneously during mitosis if Bloom syndrome is present. In comparison, the number for those who are not sick is a maximum of 6 to 10 SCE.
Further peculiarities that can be observed are aberrations that lead to symmetrical quadriradial figures . These can be recorded using conventional cytogenetic techniques. However, these quadriradials are not specific to Bloom's syndrome. They can also be observed in Fanconi anemia, among other things.
The appearance of micronuclei is a phenomenon that is observed relatively often in Bloom syndrome. These are small bulges in the cell nucleus that can almost assume the extent of a nucleus constriction. Genetic material in the form of DNA or RNA can be contained in these bulges .
The examination of the characteristic changes in Bloom syndrome or in other chromosome instability syndromes are accessible for pre- and postnatal diagnosis. The characteristics mentioned above can be recorded with conventional banding and dyeing methods. However, the maximum resolution here only affects 2 to 5 megabase pairs , so the mutations cannot be identified directly. The changes that can be detected in conventional cytogenetics therefore only represent the changes resulting from the mutations. A molecular genetic examination is therefore also of particular importance in order to make a precise statement about the causal changes.
There is currently no causal treatment strategy. The therapeutic options are limited to strict medical supervision in order to detect any malignancies that may develop at an early stage. Furthermore, special antibiotic prophylaxis and therapy are required due to the recurrent infections. A special strategy is also required in the development of vaccination schemes , as live vaccines, for example, can only be used to a limited extent and active immunization poses a particular risk here.
- RJM Gardner; Grant R. Sutherland: Chromosome abnormalities and genetic counseling. 3. Edition. Oxford University Press, 2004, ISBN 0-19-514960-2 .
- Claus-W. Wallesch (Hrsg.): Neurology: Diagnostics and therapy in clinic and practice . Elsevier Urban & Fischer, 2005, ISBN 3-437-23390-4 .