Clinical characteristics: Bloom syndrome (BSyn) is characterized by severe pre- and postnatal growth deficiency, immune abnormalities, sensitivity to sunlight, insulin resistance, and a high risk for many cancers that occur at an early age. Despite their very small head circumference, most affected individuals have normal intellectual ability. Women may be fertile but often have early menopause, and men tend to be infertile, with only one confirmed case of paternity. Serious medical complications that are more common than in the general population and that also appear at unusually early ages include cancer of a wide variety of types and anatomic sites, diabetes mellitus as a result of insulin resistance, chronic obstructive pulmonary disease, and hypothyroidism.

Diagnosis/testing: The diagnosis of BSyn is established in a proband with characteristic clinical features and biallelic pathogenic variants in BLM identified by molecular genetic testing.

Management: Treatment of manifestations: Increased-calorie-density formulas and foods may promote weight gain; consultation with gastroenterologist or feeding specialist and treatment for gastroesophageal reflux disease as needed; standard dietary treatment for dyslipidemia. Skin protection, including avoiding excessive sun exposure, sun-protective clothing and broad-brimmed hat, UV-blocking sunglasses, and use of broad-spectrum sunscreen with SPF of at least 30; standard treatment of skin cancers. Individuals with recurrent infections and defects in humoral immunity may be treated with immunoglobulins to decrease frequency and severity of infections. Developmental services and educational support as needed. In persons with cancer, modification of chemotherapy dosage and duration per oncologist. Fertility treatments as needed; standard treatment of diabetes mellitus and hypothyroidism. Cough assist devices, vibration vests, and daily nasal lavage for mucociliary clearance for bronchiectasis.

Surveillance: Monitor growth, feeding, and for gastroesophageal reflux at each visit throughout childhood; annual lipid profile beginning at age ten years. Skin exam with a dermatologist upon recognition of suspicious skin lesions and annually thereafter. Assess for recurrent, severe, or opportunistic infections at each visit. Developmental, neurobehavioral, and psychological assessment as needed. Clinical assessment for hematuria and/or abdominal mass and abdominal ultrasound examination every three months until age eight years for Wilms tumor. Screening and family education regarding signs and symptoms of leukemia and lymphoma at every health visit. Whole-body MRI every one to two years beginning at age 12 to 13 years for risk of lymphoma. Annual colonoscopy beginning at age ten to 12 years. Fecal immunochemical testing every six months beginning at age ten to 12 years. Annual breast MRI in women beginning at age 18 years. Annual fasting blood glucose and hemoglobin A1c beginning at age ten years. Annual serum TSH with reflex to thyroxine beginning at age ten years. Assess for recurrent and/or chronic pulmonary disease at each visit.

Agents/circumstances to avoid: Sun exposure to the face and other exposed skin, particularly in infancy and early childhood, should be avoided. Exposure to ionizing radiation should be minimized. Dose reductions and shortened courses of chemotherapy when needed to avoid significant side effects and toxicity (including secondary malignancies). Alkylating agents and radiation therapy are considered high risk and are avoided when possible in those with BSyn.

Evaluation of relatives at risk: It is appropriate to evaluate sibs of a proband in order to identify as early as possible those who would benefit from avoidance of sun exposure and early surveillance for cancer.

Genetic counseling: BSyn is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a BLM pathogenic variant, each sib of an affected individual has at conception a 25% chance of inheriting biallelic pathogenic variants and being affected, a 50% chance of being a heterozygote (carrier), and a 25% chance of inheriting neither of the familial pathogenic variants. Heterozygotes (carriers) are not at risk of developing BSyn; the cancer risk of heterozygotes as a group remains unclear. Once the BLM pathogenic variants have been identified in an affected family member, prenatal and preimplantation genetic testing are possible. BSyn is included on most expanded carrier screening panels.