Bloom syndrome is a very rare, genetically inherited disorder. It is characterized by increased genetic instability. Patients are short in stature and more likely to develop cancer. Because of the increased vascular markings in the tumors, Bloom syndrome is also called telangiectatic syndrome.
What is Bloom syndrome?
Bloom syndrome belongs to the group of chromosome break syndromes. Many different clinical symptoms result from dysregulation of enzymes that replicate and repair DNA. Due to defective repair mechanisms, (spontaneous) mutations accumulate in the genes. The increased mutation rate represents an increased susceptibility to cancer. Also characteristic are pre- and postnatal growth disturbance, decreased subcutaneous fat, and light-sensitive skin prone to redness and inflammation. Bloom syndrome is inherited in an autosomal recessive manner. This means that both parents must be carriers of the affected gene for your child to be clinically noticeable. The probability that the child will develop the disease is therefore statistically 25 percent. Currently, a total of 300 cases have been described. Ashkenazi Jews, however, are at increased risk for Bloom syndrome.
Causes
The cause of Bloom syndrome is a mutation in the BLM gene. This gene is RESPONSIBLE for the production of proteins such as RecQ helicases. Helicases are enzymes that cleave DNA double strands into two single strands. This process is necessary to enable replication (doubling of DNA). In this process, a second so-called sister chromosome is created from one chromosome. During DNA replication, the BLM protein monitors the sister chromosome for errors and initiates corrections. If the gene or protein is defective, mutations more often remain undetected and can cause great damage in the organism. Common changes in the genome are nucleotide insertion/deletion and non-sense mutations.
Symptoms, complaints, and signs
Patients are often proportionally short in stature and have an altered shape of the skull bones. This is already evident during pregnancy. Newborns, infants, and young children have a decreased appetite. A possible cause of this could be frequent gastroesophageal reflux, also called heartburn. In addition, Bloom syndrome patients are prone to middle ear infections, pneumonia, and aspiration of stomach contents. Infants’ skin is often normal at birth. With increasing sun exposure during the first year of life, the tendency to develop red, inflammatory skin lesions increases. The nose, cheeks, back of the hands and forearm are particularly affected. In addition, café au lait spots, benign light brown skin patches, are frequently found. Men, unlike women, are often infertile (unable to conceive). Eleven women have so far become pregnant despite the disease and have given birth to at least one healthy child. The intelligence of patients with Bloom syndrome is usually not diminished.
Diagnosis and course
The diagnosis of Bloom syndrome is considered when the following findings are present:
- An unexplained short stature as early as pregnancy that persists into adulthood; or
- A significant short stature as well as reddish skin lesions on the face after sun exposure or
- A significant short stature associated with early childhood cancer.
A genetic test is always used to confirm the diagnosis. Here, a single gene can be examined in case of suspicion or several genes. The diagnosis is confirmed if a patient has two pathological changes in the area of the BLM gene. This test can be performed before birth, as part of prenatal diagnostics. In the further course of the disease, narrowing of the ureter often occurs in men. Chronic obstructive pulmonary disease (COPD) led to death in some patients. Diabetes mellitus was diagnosed in about 50 patients, but usually without complications. Some patients developed leukemia, which was controlled by chemotherapy and radiotherapy. Cancer is the most common clinical complication. It is the most common cause of death in Bloom syndrome. Most patients developed lymphoma, a cancer of the lymphatic system. Various skin cancers are also common. Overall, 207 out of 300 patients developed cancer.
Complications
Unfortunately, no therapy exists for Bloom syndrome, which is why some symptoms and complications may occur during the course of the disease. In most cases, Bloom syndrome results in short stature. This has a negative effect on the quality of life and can lead to psychological problems and depression. In children, the short stature can also lead to teasing. It also leads to malformations and deformations of the skull, which, however, do not have a negative impact on life. The disease also causes a greatly increased sensitivity to the sun, which can lead to hypopigementation. The affected person must apply more sunscreen to prevent tumors on the skin. However, the hypopigmentation does not lead to further complications. Due to the Bloom syndrome, the patient has an increased susceptibility to infections due to a weakened immune system. Affected individuals often develop inflammations and infections that would not cause disease in healthy individuals. Immunodeficiencies result in reduced life expectancy. Likewise, leukemias can occur during life, leading to pain and severe limitations in everyday life.
When should you see a doctor?
In most cases, the symptoms of Bloom syndrome appear relatively early in the affected person’s childhood. A doctor should be seen immediately, as patients with this syndrome are more likely to develop cancer. Regular examinations are also necessary. A doctor should be consulted if the patients suffer from short stature. Altered bones in the skull or reflux disease may also indicate Bloom syndrome and should be examined. Furthermore, constant inflammation in the ears or pneumonia may also indicate this syndrome and must also be investigated. Patients also suffer from skin lesions due to sun exposure, which must also be treated to prevent skin cancer. The inability of patients with Bloom syndrome to conceive usually cannot be treated. The diagnosis of the syndrome is made by a pediatrician or general practitioner. However, further treatment is carried out by the respective specialist. The earlier the treatment of the syndrome begins, the higher the life expectancy of the patient.
Treatment and therapy
A curative, i.e., curative therapy, is currently not available. Approaches for this would be gene therapies. Rather, the therapy is in precaution of complications. A thorough physical examination is necessary and complications can be detected and treated early. Gastroesophageal reflux can be treated with a proton pump inhibitor, such as pantoprazole. Regular checks of blood glucose levels could prevent diabetes mellitus or reduce the sequelae of diabetes mellitus. To check the immune system, immunoglobulin concentrations are measured in the blood plasma. Men should have regular urological examinations. Patients under 20 should be screened regularly for leukemia. Colorectal cancer should also be specifically screened for, as this is the most common solid tumor in humans. At least one colonoscopy should be performed each year. Fecal examination for blood should be done two to four times a year. Psychosocial support for the patient and family is also important. A serious, chronic disease not only puts a strain on the patient, but also always on his or her relatives. Joint discussions promote the relationship and increase the success of therapy.
Outlook and prognosis
With the current medical and scientific possibilities, Bloom syndrome is not curable. Therefore, the prognosis for this disease is considered unfavorable. To date, the gene mutation cannot be cured with existing therapeutic options. For legal reasons, intervention in human genetics is not permitted. This reduces the prospect of a permanent cure. In the case of Bloom syndrome, treatment is aimed in particular at reducing the accompanying symptoms. In addition, various screening tests are offered, which are used for a timely diagnosis for possible tissue changes. Due to Bloom’s syndrome, patients suffer more frequently tumor diseases with a malignant course. Young people in particular are affected and should have appropriate tests performed at regular intervals.Even if the disease cannot be cured, there are ways in which the patient’s general well-being can be improved. Relaxation techniques, psychotherapeutic support and a healthy lifestyle help to strengthen the organism and build up the courage to face life. This is helpful in order to better cope with the disease in everyday life and to have sufficient resources when the after-effects of Bloom’s syndrome arise. With a strengthened and stable immune system, the patient is better able to mobilize necessary defenses and reduce the healing path in further illnesses.
Prevention
Genetic counseling sessions and examinations can help families find out if there is a relevant risk for a genetic, hereditary disease. Genomic testing takes place in addition to an educational interview. The results can help families better plan their family. To reduce the risk of spontaneous mutations, a healthy, active lifestyle is recommended. Smoking and an unhealthy diet should be avoided, as these increase the likelihood of a mutation. Late pregnancies always have an increased risk of genetic disease in the child.
Follow-up
Rarely occurring congenital teleangiectatic syndrome is one of the chromosome break syndromes. Because of this and the serious damage, treatment and follow-up are more difficult. Hopefully, gene therapy will be able to anticipate such damage prenatally in the future. The possibilities of aftercare mostly concern single symptoms or consequential damages of the Bloom syndrome. Rather, preventive measures are important because patients with Bloom syndrome often develop cancer due to the associated gene mutations. In addition, thanks to the high tendency to infection, preventive measures in the form of antibiotic prophylaxis as well as a subsequent build-up of the intestinal flora for the purpose of better immune activity may be necessary. In the case of frequently occurring problems such as the reflux syndrome, acute middle ear or lung infections, something can be done with follow-up care. High sensitivity to light, which leads to various skin damages, can also be treated dermatologically during aftercare. Prevention is just as necessary, however, as there is an increased tendency for skin cancer. If this is operated on, wound care in aftercare is just as important as regular screening for new skin cancer foci. Compared to live vaccines, there is a limited usability in Bloom syndrome. Therefore, preventive care against certain diseases such as influenza is more important than any follow-up care. If a preventable disease nevertheless breaks out because of the problems with live vaccines, follow-up care is unavoidable. It depends on the type and severity of the disease.
What you can do yourself
Bloom syndrome cannot yet be treated causally. Therapy focuses on relieving the symptoms and discomfort. However, patients suffering from the disease can take some measures to support medical treatment and positively influence the healing process. First of all, a specialist should be consulted with Bloom’s syndrome. Since the disease can manifest itself in different ways and often progresses very differently, expert advice is needed. In most cases, several examinations are necessary, which is why the patient should make appropriate arrangements for a longer stay in the clinic. After the therapy has been determined, the patient should take it easy. Moderate physical exercise is useful to strengthen the immune system. A healthy diet reduces the risk of secondary diseases and improves well-being. Patients under 20 should have regular check-ups. Since there is an increased risk of leukemia or colorectal cancer, attention should be paid to conspicuous symptoms in these areas. If, for example, there is a non-specific pressure pain in the gastrointestinal tract, this should be clarified. Psychological support for the patient and his relatives is also important. A serious illness places an enormous burden on those affected, which must be dealt with. Joint discussions improve the patient’s mental state and often have a positive effect on the course of the disease.
