Bloom syndrome is a rare genetic disorder characterized by short stature, a predisposition to develop various cancers, and a characteristic facial appearance. It is caused by mutations in the BLM gene, which maintains genomic stability by helping repair DNA damage. Bloom syndrome is inherited in an autosomal recessive manner, meaning an individual must inherit two copies of the mutated gene (one from each parent) to manifest the disorder. The overall prevalence of the disease is unknown, but it is most prevalent in the Jewish or Ashkenazi population, where it is estimated at approximately 1 in 48.000 births.
Bloom syndrome genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximetaly 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).
Key features and aspects of Bloom syndrome include:
- Growth Deficiency: Individuals with Bloom syndrome typically exhibit short stature. The growth deficiency becomes apparent in early childhood and persists throughout life.
- Facial Features: The syndrome is associated with a distinctive facial appearance, including a long, narrow face, a prominent nose, and a small lower jaw.
- Skin Abnormalities: Bloom syndrome is characterized by photosensitivity, which means individuals are more sensitive to sunlight. The skin may develop a rash or reddening when exposed to sunlight.
- Immunodeficiency: Individuals with Bloom syndrome may be more susceptible to infections due to immune system abnormalities.
- Chromosomal Instability: One of the defining features of Bloom syndrome is chromosomal instability, leading to an increased frequency of breaks and rearrangements in the DNA. This can result in an elevated risk of developing various cancers.
- Cancer Predisposition: Individuals with Bloom syndrome have a significantly increased risk of developing cancer, particularly leukemia and a variety of solid tumors. The risk of cancer increases with age.
- Fertility Issues: Both males and females with Bloom syndrome may experience fertility issues, including difficulty conceiving and an increased risk of miscarriages.
- Management and Surveillance: There is no cure for Bloom syndrome, and management focuses on addressing specific symptoms and providing supportive care. Regular surveillance for cancer and early detection are crucial components of care. Due to the complex nature of Bloom syndrome, a multidisciplinary approach involving geneticists, oncologists, dermatologists, and other specialists is often necessary to provide comprehensive care. Regular monitoring and proactive management of potential complications are essential for individuals with Bloom syndrome. Genetic counseling is recommended for families affected by Bloom syndrome to understand the inheritance pattern and assess the risk for future generations.
Diagnosis is confirmed through genetic testing to identify mutations in the BLM gene. Prenatal testing is available for families at risk.
Bloom syndrome is a rare autosomal recessive disorder caused by mutations in the BLM gene that codes for a protein called RecQ helicase. Helicases are proteins that bind directly to DNA to relax its coiling, and this action is necessary for multiple processes such as cell division and DNA damage repair.
The c.2207_2212delinsTAGATTC mutation (p.Tyr736fs) is the most frequent disease-causing variant, especially in the Jewish Ashkenazi population, occurring in 1 in 111 individuals. This mutation consists of the deletion of 6 and subsequent insertion of 7 nucleotides in exon 10, causing an alteration of the reading pattern and the appearance of an early stop codon. Therefore, a truncated or absent non-functional protein is generated. In patients, this mutation has been observed in homozygosis.
Other variants that occur recurrently in specific populations have been described. The variants c.2923del (p.Gln975fs) and c.2695C>T (p.Arg899Ter) have been identified as founders in non-Italian Europeans and North Americans. The c.557_559del mutation (p.Ser186_Lys187delinsTer) is most frequently found in Japanese, while the c.2506_2507del variant (p.Arg836fs) is common in Americans of Spanish ancestry.
Patients who carry one copy of a pathogenic variant in the BLM gene do not show the symptomatology of the disease. However, certain studies suggest that they have an increased risk of developing breast or prostate cancer or colorectal cancer.
The genetic test of Bloom syndrome analyzes the nine most frequent pathogenic mutations of BLM gene.
With the technique used for genetic testing, only the gene's specific mutations, which are the most important and frequent in the literature, are analyzed. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested, which cannot be identified with this method. Different analysis techniques can be used for these cases, such as, e.g., next-generation sequencing (NGS).
