Fecha de publicación: -- Fuente: PubMed "hive" 2026 Sep 29. In: Adam MP, Bick S, Mirzaa GM, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2026.ABSTRACTCLINICAL CHARACTERISTICS: Primary familial gastrointestinal stromal tumors (GIST) are characterized by the presence of typically multifocal GIST that most often involve the stomach. Additional gastrointestinal (GI) manifestations can include inflammatory fibroid polyps most often in the stomach or small bowel and interstitial cell of Cajal hyperplasia occurring throughout the GI tract. Skin hyperpigmentation typically involving the neck, face, axillae, groin, and perineum that appears in childhood or adolescence is common. Additional integument findings can include increased nevi, lentigines, and multiple café au lait macules. Less common features include urticaria pigmentosa, cutaneous mastocytosis, and systemic mastocytosis.DIAGNOSIS: The diagnosis of primary familial GIST can be established in a proband with a pathologically confirmed diagnosis of GIST and a heterozygous gain-of-function pathogenic variant in KIT or PDGFRA identified by molecular genetic testing.MANAGEMENT: Targeted therapies: Treatment of GIST includes tyrosine kinase inhibitors imatinib or avapritinib; response to treatment varies by gene and genotype.Supportive care: Multidisciplinary management of GIST includes consideration of surgical resection and tyrosine kinase inhibitor; endoscopic polypectomy of inflammatory fibroid polyps to prevent symptoms and complications; treatment of urticaria pigmentosa and cutaneous mastocytosis per dermatologist or allergist; treatment of systemic mastocytosis includes symptom control, trigger avoidance, antihistamines, and novel targeted therapies with premedication prior to known triggers; endoscopic management of dysphasia as needed. In those with PDGFRA-related GIST plus syndrome, management of early tooth loss per dentist, orthodontist, and oral surgeon as needed.Surveillance: At least annual examination for pain, bowel obstruction, rectal bleeding, dysphagia, and bloating; abdominal/pelvis CT with contrast or MRI beginning at age 18 years; endoscopy as needed; clinical examination for skin manifestations at least annually; clinical examination for mastocytosis and counseling regarding mast cell trigger avoidance at least annually; evaluation with dermatologist, hematologist, and/or allergist as needed; clinical examination for manifestations of dysphasia at least annually; endoscopy and esophageal function studies as needed; follow-up genetic counselling as needed.Agents and circumstances to avoid: Individuals with evidence of mastocytosis should avoid mast cell triggers: Hymenoptera stings, medications (e.g., nonsteroidal anti-inflammatory drugs, opioids, vancomycin, quinolone, certain antibiotics, various anesthetic agents), extreme temperatures, and environmental factors.Evaluation of relatives at risk: Offer molecular genetic testing for the familial KIT or PDGFRA pathogenic variant to apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from surveillance, diagnosis, and treatment.Pregnancy management: Pregnant individuals should be followed by high-risk obstetrics, anesthesiologists, and allergy specialists. Imatinib is not recommended during pregnancy, especially the first trimester. Avapritinib should be avoided in pregnancy. Mast cell triggers should be avoided with epinephrine available as needed during labor and delivery.GENETIC COUNSELING: Primary familial GIST is inherited in an autosomal dominant manner. The majority of individuals diagnosed with primary familial GIST have an affected parent. Each child of an affected individual has a 50% chance of inheriting the KIT or PDGFRA pathogenic variant. Once the primary familial GIST-related pathogenic variant has been identified in an affected family member, predictive molecular genetic testing of at-risk relatives and prenatal/preimplantation genetic testing are possible.PMID:42809666 | Bookshelf:NBK625142