Subject(s)
Bloom Syndrome , Dwarfism , Exome Sequencing/methods , Growth Hormone/adverse effects , RecQ Helicases/genetics , Bloom Syndrome/diagnosis , Bloom Syndrome/genetics , Bloom Syndrome/physiopathology , Bloom Syndrome/therapy , Brachydactyly/diagnosis , Brachydactyly/genetics , Child, Preschool , Contraindications, Drug , Diagnosis, Differential , Dwarfism/diagnosis , Dwarfism/drug therapy , Dwarfism/genetics , Female , Genetic Association Studies , Growth Charts , Growth Hormone/therapeutic use , Homozygote , Humans , Micrognathism/diagnosis , Micrognathism/genetics , Neoplasms/etiology , Neoplasms/prevention & control , Risk Reduction Behavior , Skin Abnormalities/diagnosis , Skin Abnormalities/geneticsABSTRACT
Bloom Syndrome (BSyn) is an autosomal recessive disorder that causes growth deficiency, endocrine abnormalities, photosensitive skin rash, immune abnormalities, and predisposition to early-onset cancer. The available treatments for BSyn are symptomatic, and early identification of complications has the potential to improve outcomes. To accomplish this, standardized recommendations for health supervision are needed for early diagnosis and treatment. The purpose of this report is to use information from the BSyn Registry, published literature, and expertise from clinicians and researchers with experience in BSyn to develop recommendations for diagnosis, screening, and treatment of the clinical manifestations in people with BSyn. These health supervision recommendations can be incorporated into the routine clinical care of people with BSyn and can be revised as more knowledge is gained regarding their clinical utility.
Subject(s)
Bloom Syndrome/epidemiology , Delivery of Health Care , Bloom Syndrome/complications , Bloom Syndrome/diagnosis , Bloom Syndrome/therapy , Child , Child Development , Child, Preschool , Delivery of Health Care/history , Delivery of Health Care/organization & administration , Disease Management , Female , Health Planning Guidelines , History, 20th Century , History, 21st Century , Humans , Incidence , Intelligence , Male , Neoplasms/diagnosis , Neoplasms/epidemiology , Neoplasms/etiology , Neoplasms/therapy , Nutritional Status , Phenotype , Public Health Surveillance , RegistriesABSTRACT
Bloom syndrome (BS) is a rare, autosomal recessive genetic disorder characterized by short stature, a skin rash associated with sun exposure, and an elevated likelihood of developing cancers of essentially all types, beginning at an early age. Cancer is the leading cause of death for persons with BS, and its early onset results in a reported median lifespan of <30 years. With fewer than 300 documented cases since BS was first described in 1954, its rarity has challenged progress in advancing both the care of and the cure for persons with BS. Presently, there are no known clinically actionable targets specific to persons with this cancer predisposition syndrome, despite the fact that standard cancer treatments are often contraindicated or must be substantially modified for persons with BS. Herein, Zachary Rogers recounts his experience as a cancer patient with BS contemplating a substantially customized chemotherapy regimen that highlights the need for development of individualized treatments in the BS community. We also outline a patient-centered research and community action road map with the goal of improving and prolonging the lives of persons with Bloom syndrome, including the facilitation of precision medicine development specific to this condition.
Subject(s)
Bloom Syndrome/diagnosis , Bloom Syndrome/epidemiology , Bloom Syndrome/therapy , Family , Health Priorities , History, 20th Century , History, 21st Century , Humans , Precision Medicine/methods , ResearchABSTRACT
Hereditary photodermatoses are a spectrum of rare photosensitive disorders that are often caused by genetic deficiency or malfunction of various components of the DNA repair pathway. This results clinically in extreme photosensitivity, with many syndromes exhibiting an increased risk of cutaneous malignancies. This review will focus specifically on the syndromes with malignant potential, including xeroderma pigmentosum, Bloom syndrome, and Rothmund-Thomson syndrome. The typical phenotypic findings of each disorder will be examined and contrasted, including noncutaneous identifiers to aid in diagnosis. The management of these patients will also be discussed. At this time, the mainstay of therapy remains strict photoprotection; however, genetic therapies are under investigation.
Subject(s)
DNA Repair-Deficiency Disorders/genetics , Neoplastic Syndromes, Hereditary/genetics , Photosensitivity Disorders/genetics , Skin Neoplasms/genetics , Bloom Syndrome/enzymology , Bloom Syndrome/epidemiology , Bloom Syndrome/genetics , Bloom Syndrome/therapy , DNA Repair , DNA Repair Enzymes/deficiency , DNA Repair Enzymes/genetics , DNA Repair-Deficiency Disorders/epidemiology , Genes, Recessive , Genetic Predisposition to Disease , Humans , Neoplasms, Radiation-Induced/etiology , Neoplasms, Radiation-Induced/genetics , Neoplastic Syndromes, Hereditary/epidemiology , Phenotype , Proliferating Cell Nuclear Antigen/genetics , Rothmund-Thomson Syndrome/enzymology , Rothmund-Thomson Syndrome/epidemiology , Rothmund-Thomson Syndrome/genetics , Rothmund-Thomson Syndrome/therapy , Skin Neoplasms/etiology , Sunlight/adverse effects , Ultraviolet Rays/adverse effects , Xeroderma Pigmentosum/enzymology , Xeroderma Pigmentosum/epidemiology , Xeroderma Pigmentosum/genetics , Xeroderma Pigmentosum/therapyABSTRACT
Bloom Syndrome (BS, MIM #210900) is an autosomal recessive genetic disorder caused by a mutation in the BLM gene, which codes for the DNA repair enzyme RecQL3 helicase. Without proper DNA repair mechanisms, abnormal DNA exchange takes place between sister chromatids and results in genetic instability that may lead to cancer, especially lymphoma and acute myelogenous leukemia, lower and upper gastrointestinal tract neoplasias, cutaneous tumors, and neoplasias in the genitalia and urinary tract. BS patients are usually of Ashkenazi Jewish descent and exhibit narrow facial features, elongated limbs, and several dermatologic complications including photosensitivity, poikiloderma, and telangiectatic erythema. The most concerning manifestation of BS is multiple malignancies, which require frequent screenings and strict vigilance by the physician. Therefore, distinguishing between BS and other dermatologic syndromes of similar presentation such as Rothmund-Thomson Syndrome, Erythropoietic Protoporphyria, and Cockayne Syndrome is paramount to disease management and to prolonging life. BS can be diagnosed through a variety of DNA sequencing methods, and genetic testing is available for high-risk populations. This review consolidates several sources on BS sequelae and aims to suggest the importance of differentiating BS from other dermatologic conditions. This paper also elucidates the recently discovered BRAFT and FANCM protein complexes that link BS and Fanconi anemia.
Subject(s)
Bloom Syndrome/diagnosis , Bloom Syndrome/genetics , Bloom Syndrome/therapy , Diagnosis, Differential , Humans , PrognosisABSTRACT
Bloom's syndrome is an autosomal recessive disorder characterized by intrauterine growth retardation, typical physical signs, immunodeficiency and an increased risk of developing neoplasms at a young age, compared to the general population. Factors possibly involved in the pathogenesis of non-endemic Burkitt's lymphoma in a five year old girl with Bloom's syndrome are discussed. These include immunodeficiency, upregulated c-myc expression and an Epstein-Barr viral infection.
