| 56 57 | See page 67 for references BARD1 gene summary BARD1-associated hereditary cancer Gene name BARD1 Associated syndrome BARD1-associated hereditary cancer Primary associated cancers Breast, ovarian Frequency Unknown Inheritance pattern Autosomal dominant Overview · ·BARD1 mutations have primarily been studied in association with breast and ovarian cancer; however, the strength of these associations is unclear. · ·Because BARD1 cancer risks are not fully understood and because mutations may not fully explain the cancer risk in a family, patients and their relatives may or may not benefit from this information. Additionally, family members who test negative for a known familial BARD1 mutation may still be at increased risk for cancer based on the family history. About BARD1 The BRCA1 gene provides instructions for making a protein called BRCA1-associated RING domain. As the name suggests, BARD1 interacts with BRCA1 and specifically the N-terminal region of BRCA1. The formation of a stable complex between BARD1 and BRCA1 is believed to be an essential aspect of BRCA1 tumor suppression and as such, mutations in BARD1 have recently been studied in association with breast and ovarian cancer. Studies to date have identified BARD1 mutations in both breast and ovarian cancer cases. The exact cancer risks remain unknown but are likely in the low to moderate range. BARD1 gene mutations have also been reported to a lesser extent with other cancer types such as neuroblastomas, colorectal cancer, and lung cancer. · ·Paragangliomas · ·Pancreatic cysts that can rarely cause endocrine or exocrine insufficiency or obstruction. · ·Endolymphatic sac tumors are seen in 10-16% of individuals with VHL and can lead to unilateral or bilateral hearing loss. · ·Epididymal cystadenomas are common in males with VHL and can rarely cause infertility. Potential management options The VHL Family Alliance has worked extensively with healthcare professionals to assemble guidelines that are generally accepted throughout the world. It should be noted that these guidelines are not evidence based and rely on experiential reporting. · ·Starting at age 1 year: perform annual evaluation for neurologic symptoms, vision problems, and hearing disturbance; annual blood pressure monitoring; annual ophthalmology evaluation. · ·Starting at age 5 years: perform annual blood or urinary fractionated metanephrines; audiology assessment every 2 to 3 years; thin-slice MRI with contrast of the internal auditory canal in those with repeated ear infections. · ·Starting at age 16 years: perform annual abdominal ultrasound and every other year MRI scan of the abdomen; MRI of the brain and total spine every 2 years. To determine the extent of disease in newly diagnosed individuals with VHL, consider the following assessments: · ·Neurologic examination and review of medical history. · ·MRI of the brain and spine. · ·Comprehensive eye evaluation with an ophthalmologist. · ·Hearing evaluation with audiologist. · ·Blood pressure check and urine screening for hormone levels. · ·Abdominal ultrasound after 16 years of age with additional follow-up imaging (MRI or CT) based on ultrasound findings. · ·A consultation with a genetics specialist.