Bloom syndrome (BSyn) is a rare hereditary disease with an autosomal recessive transmission mechanism, which is manifested by growth retardation, telangiectatic erythema, reduced immune reactivity. Patients, as a rule, develop lung lesions, reproductive function disorders, and a predisposition to malignant neoplasms is observed. The syndrome is diagnosed pre- and postnatally. The most informative is molecular genetic research. Treatment is symptomatic: antibiotics, immunoglobulins, antisecretory agents are used, chemoradiotherapy is indicated for oncopathology.
The syndrome was named after the American dermatologist David Bloom, who described the characteristic clinical signs in three patients in 1954. Cytogenetic features of the disease were identified by the American geneticist James Herman in 1965, and molecular genetic causes were established in 1995. By 2009, 265 patients were registered in the world. In 25% of all cases of pathology, the syndrome occurs in Ashkenazi Jews (frequency 1:48000). Men are more susceptible to the disease, they account for up to 80% of all sufferers of Bloom’s disease.
The syndrome is caused by a mutation of the BLM gene located on the long arm of chromosome 15 and encoding the enzyme DNA helicase RecQI3. For the manifestation of the disease, it is necessary that violations of the nucleotide sequence occur in both alleles of the gene. The pathology has an autosomal recessive type of inheritance, the carriage of one mutant allele is detected in approximately 1% of Ashkenazi Jews. The main risk factor is closely related marriages.
The main role in the mechanism of the disease is played by damage to the enzyme DNA helicase, which is involved in the processes of DNA doubling. The enzyme also prevents and eliminates spontaneous mutations of the genetic code that occur during violations of molecular replication processes, the action of mutagenic factors. When the BLM protein mutates, an inactive enzyme is synthesized, which ceases to control cell division.
In patients who suffer from the disease, the process of formation of “sister” chromatids, which normally form a DNA strand, is disrupted. Bloom syndrome is characterized by a 10-fold increased frequency of exchanges of genetic material between two chains of nucleotides, which is accompanied by damage to the chromosomal structure, the appearance of spontaneous point mutations.
With Bloom syndrome, there are typical phenotype changes that are noticeable already in early childhood. It is characterized by an elongated head shape (dolichocephaly), an excessively narrow face with simultaneous enlargement of the nose and ear cartilages. In children, the pace of physical development is disrupted: the maximum value of growth in Bloom’s disease is about 150 cm, but the proportions of the body are normal. Due to the lack of subcutaneous tissue, patients look unnecessarily thin.
From an early age, photodermatitis appears on the skin — a red rash with areas of capillary expansion (telangiectasia). Rashes are provoked by exposure to ultraviolet light. Skin changes are mainly localized in the middle third of the face according to the “butterfly” type. As the child grows, the rash areas spread to the shoulders, forearms, and back of the hands. Also typical are dark spots alternating with foci of depigmentation.
Patients with Bloom syndrome often have cognitive impairments in the form of memory loss, impaired concentration, children have a lack of motivation and interest in learning. At the same time, intelligence is within normal limits, mental retardation is not characteristic. The genetic disease is associated with decreased vision on the background of chronic conjunctivitis, bilateral hypoplasia of the optic nerve.
The most dangerous consequence of Bloom syndrome is considered to be a high risk of carcinogenesis. Patients of childhood and adolescence mainly develop oncohematological diseases — leukemia, lymphoma, as well as rare types of neoplasms, such as osteogenic sarcoma, Wilms tumor. In adults, intestinal and esophageal adenocarcinomas are more often formed, women are predisposed to breast cancer.
Due to a decrease in immunity, patients are concerned about recurrent infections: bronchitis, pneumonia, gastroenteritis, the risk of opportunistic infections (pneumocystis, candidiasis) increases. In 15% of cases, type 2 diabetes occurs in adulthood. In men, the syndrome is often complicated by hypogenitalism, underdevelopment of the testicles, azoospermia. Women suffer from ovarian dysfunction, dysmenorrhea or amenorrhea, early menopause.
Examination of a patient with suspected Bloom syndrome is performed with the participation of a dermatologist, geneticist, endocrinologist, according to the indications, a gastroenterologist, oncologist, immunologist are involved in the examination. At the initial consultation, specific phenotypic changes that indicate genetic pathology are determined, and the family history is carefully clarified. To accurately diagnose the syndrome, the following research methods are prescribed:
- Genetic testing. Bloom syndrome is verified by molecular genetic examination of the genome for the mutated BLM gene, cytogenetic diagnosis of the frequency of exchange between sister chromatids. In high-risk families, an antenatal genetic study is possible with chorionic biopsy or amniocentesis.
- Instrumental visualization. To detect chronic pathologies of the respiratory system, chest x-ray, CT of the lungs, bronchoscopy are performed. With symptoms from the gastrointestinal tract, EFGDS, ultrasound of the abdominal cavity are performed. If possible, non-radiation diagnostic methods are used in order not to provoke skin tumors.
- Additional laboratory methods. In case of recurrent infections, an extended immunogram is used to assess humoral and cellular immunity. Regular monitoring of blood glucose is necessary for the timely detection of diabetes mellitus. Unexplained anemia in the hemogram results may indicate oncopathology.
Patients with BSyn are recommended symptomatic treatment, which is selected taking into account the severity of clinical manifestations, the presence of complications. Most often, Bloom’s syndrome is accompanied by infections, for the correction of which antibiotics, immunomodulators are prescribed, and in severe immunodeficiency, replacement administration of serum immunoglobulins is used. Other areas of treatment:
- Correction of metabolic parameters. If glucose metabolism is impaired, oral hypoglycemic drugs are taken. For some patients, an insulin therapy regimen is selected to control diabetes mellitus.
- Support of the gastrointestinal tract. With gastroesophageal reflux, usually concomitant with Bloom’s disease, proton pump inhibitors, antacids, H2-histamine blockers are indicated. Enzymes, probiotics, and prebiotics are used to stimulate digestion.
- Chemoradiotherapy. It is carried out when Bloom’s syndrome is complicated by cancer. Due to the high frequency of allergic reactions, patients need gentle treatment options with reduced radiation doses.
- The use of sanskrins. To minimize photodermatitis, to prevent malignant skin neoplasms, patients who have the syndrome should be applied year-round to open areas of the body with SPF 30 or more.
Of great importance in therapy is the correction of lifestyle, the elimination of modifiable risk factors for cancer. Patients are advised to give up smoking, avoid carcinogens in food, cosmetics, household chemicals. Regular checkups with a dermatologist, therapist, pulmonologist are necessary. Patients and their relatives undergo genetic counseling, receive recommendations on family planning.
Prognosis and prevention
Bloom’s syndrome is an incurable disease, and symptomatic therapy can only prolong the life expectancy of patients. Patients die before the age of 50 from oncopathologies, chronic lung diseases, systemic infections provoked by immunodeficiency. Primary prevention is represented by medical and genetic counseling for families from risk groups, and secondary prevention includes timely diagnosis and adequate supportive treatment.