Cancer Surveillance in Gorlin Syndrome and Rhabdoid Tumor Predisposition Syndrome

Abstract

Gorlin syndrome and rhabdoid tumor predisposition syndrome (RTPS) are autosomal dominant syndromes associated with an increased risk of childhood-onset brain tumors. Individuals with Gorlin syndrome can manifest a wide range of phenotypic abnormalities, with about 5% of family members developing medulloblastoma, usually occurring in the first 3 years of life. Gorlin syndrome is associated with germline mutations in components of the Sonic Hedgehog pathway, including Patched1 (PTCH1) and Suppressor of fused (SUFU). SUFU mutation carriers appear to have an especially high risk of early-onset medulloblastoma. Surveillance MRI in the first years of life in SUFU mutation carriers is, therefore, recommended. Given the risk of basal cell carcinomas, regular dermatologic examinations and sun protection are also recommended. Rhabdoid tumors (RT) are tumors initially defined by the descriptive “rhabdoid” term, implying a phenotypic similarity with rhabdomyoblasts at the microscopic level. RTs usually present before the age of 3 and can arise within the cranium as atypical teratoid/rhabdoid tumors or extracranially, especially in the kidney, as malignant rhabdoid tumors. However, RTs of both types share germline and somatic mutations in SMARCB1 or, more rarely, SMARCA4, each of which encodes a chromatin remodeling family member. SMARCA4 mutations are particularly associated with small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). The outcome following a diagnosis of any of these tumors is often poor, and the value of surveillance is unknown. International efforts to determine surveillance protocols are underway, and preliminary recommendations are made for carriers of SMARCB1 and SMARCA4 mutations. Clin Cancer Res; 23(12); e62–e67. ©2017 AACR. See all articles in the online-only CCR Pediatric Oncology Series.

Co‐occurrence of schwannomatosis and rhabdoid tumor predisposition syndrome 1

“…Our results nevertheless imply that microstructural MRN is a method well suited to detecting subclinical peripheral nerve pathology in clinically unaffected SMARCB1 mutation carriers such as proband I.5. According to the recommended surveillance protocols for patients with AT/RT and truncating germline SMARCB1 mutations, whole‐body MRI should be considered up to the age of 5 years (Foulkes et al, ). Our findings suggest that long‐term survivors of AT/RT and truncating germline SMARCB1 mutations should receive regular surveillance for schwannomatosis‐associated clinical symptoms.…”

Malignant progression of a peripheral nerve sheath tumor in the setting of rhabdoid tumor predisposition syndrome

“…Foulkes et al. recently provided guidelines for cancer screening in RTPS . Worsening symptoms, coupled with detection of a germline alteration in the mother, prompted her to seek immediate medical attention for neurological problems.…”

Cardiac Fibroma with Ventricular Tachycardia: An Unusual Clinical Presentation of Nevoid Basal Cell Carcinoma Syndrome

“…These recommendations are important for reducing basal cell carcinoma development, decreasing the risk for associated malignancies, and identifying potential complications of NBCCS early [Bree et al, 2011]. Additionally, cancer surveillance guidelines were recently published for individuals with NBCCS [Foulkes et al, 2017].…”