Bloom syndrome (OMIM#210900, ORPHA:125) is a multisystem genetic disorder that increases the risk of cancer at all ages. The disease is extremely rare (no available prevalence estimate), except for individuals of Ashkenazi Jewish ancestry, where the prevalence may be about 1/48000. The main clinical manifestations are:
BS is caused by germline alterations in the BLM gene, that is involved in the maintenance of genomic stability. The disease is diagnosed by clinical manifestations and the detection of alterations in both copies of the BLM gene. A specialized genetic test (sister chromatid exchanges) can also be useful for the diagnosis.
BS is inherited in an autosomal recessive way, which means that an affected individual has both copies of the BLM gene affected, inherited from parents who are both healthy carriers. The risk of having an affected child for a couple who already has a child with BS is 25% (or 1 in 4). For an individual affected with BS the risk of having an affected child is overall low, since the partner also has to be a carrier. The condition is usually associated with infertility in affected males.Prenatal and preimplantation genetic diagnoses are possible if causative pathogenic variants have been identified in the parents (different legal/ethical perspectives could exist).
Individuals should be advised to avoid exposure to sunlight and protect/cover adequately exposed skin. Whenever possible imaging based on use of ionizing radiations should be avoided, due to the presumed cancer risk associated with chromosome instability.