Bloom syndrome is a rare, inherited disorder that affects multiple body systems, causing severe growth deficiencies and heightened susceptibility to various health issues. It is classified as a chromosomal breakage syndrome, indicating a fundamental problem with the stability of a person’s genetic material. This condition is characterized by a lifelong vulnerability to disease, particularly infections and malignancy, and is present from birth. Understanding Bloom syndrome provides insight into the complex mechanisms that protect the integrity of our DNA.
Genetic Basis and Inheritance
Bloom syndrome is caused by mutations in the BLM gene, located on chromosome 15. This gene provides instructions for creating the Bloom syndrome protein, which is part of the RecQ helicase family of enzymes. The protein’s normal function is to help unwind and manage the double-stranded DNA molecule during replication and repair processes, acting as a “caretaker of the genome.”
When the BLM gene is mutated, the resulting protein is non-functional or absent, leading to a significant increase in chromosomal breakage and rearrangement. Cells from affected individuals exhibit striking genomic instability, with a spontaneous mutation rate that is significantly higher than average.
The disorder is inherited in an autosomal recessive pattern, meaning an individual must inherit a mutated copy of the BLM gene from both parents. Parents who carry one copy of the mutated gene are typically unaffected and are called carriers. When two carriers have a child, there is a one in four chance the child will be born with Bloom syndrome.
Defining Physical Characteristics
The condition’s effects on growth are apparent early, presenting as severe pre- and postnatal growth deficiency. Affected individuals are typically smaller than 97% of the general population in both height and weight from birth onward, resulting in proportional short stature. The adult height for most affected individuals rarely exceeds five feet.
A distinctive physical feature is a photosensitive skin rash, which often appears in early childhood, typically around one or two years of age. This rash is telangiectatic erythema—a red, inflamed patch of skin with small, enlarged blood vessels—that primarily occurs on sun-exposed areas like the face. It often presents in a butterfly pattern across the cheeks and nose, worsening with continued exposure to ultraviolet light.
Characteristic facial features include a long, narrow face and a small lower jaw, sometimes referred to as micrognathia. Individuals may also have prominent noses and ears. Another common trait is a high-pitched voice.
Associated Health Complications
The genomic instability caused by the BLM mutation creates a predisposition to serious health complications, most notably cancer. Individuals with Bloom syndrome have a risk of developing cancer that is estimated to be 150 to 300 times higher than that of the general population. These malignancies tend to arise at an unusually early age, and affected individuals can develop almost any type of cancer.
Over 50% of people with the condition develop at least one cancer in their lifetime, often developing multiple primary tumors. Leukemias and lymphomas are common, particularly in childhood and young adulthood. Solid tumors like colorectal and skin cancers also occur frequently and at a much younger age than typically seen. The risk of malignancy is directly linked to the instability of the genome, where the increased rate of chromosomal damage and somatic mutations increases the likelihood of cancerous cell transformation.
The condition also involves mild immune system abnormalities, making affected individuals more prone to frequent and severe infections. This immunodeficiency is characterized by lower levels of immunoglobulins, the antibodies necessary to fight off pathogens. Recurrent infections of the respiratory tract, ears, and lungs are common during infancy and childhood.
Other complications include an increased risk of developing type 2 diabetes due to insulin resistance. Chronic obstructive pulmonary disease can also occur, often resulting from repeated respiratory infections.
Diagnosis and Ongoing Care
Diagnosis of Bloom syndrome is typically suspected based on the presence of cardinal clinical features, such as severe growth deficiency and the characteristic sun-sensitive facial rash. Confirmation is established through genetic testing, which identifies biallelic pathogenic variants in the BLM gene. While historically a laboratory test showing increased sister chromatid exchanges (SCEs) was used, genetic sequencing is now the standard for definitive diagnosis.
Ongoing care requires a multidisciplinary approach focused on managing symptoms and proactively addressing major risks. Due to the elevated cancer risk, rigorous cancer surveillance protocols are implemented early in life. These screenings may include frequent physical examinations and specific imaging, such as abdominal ultrasounds every few months to screen for tumors like Wilms tumor.
Regular monitoring for hematologic malignancies and early-onset colorectal and breast cancer is also incorporated into the care plan. Management of recurrent infections may involve antibiotics or, for significant antibody deficiency, immunoglobulin replacement therapy.
Because of the underlying DNA repair defect, affected individuals may exhibit hypersensitivity to radiation and certain chemotherapy drugs. This necessitates careful adaptation of cancer treatment if malignancy occurs. Sun protection is also necessary to minimize the severity of the rash and reduce the risk of skin cancer.