Clinicopathological and molecular spectrum of patients with germline SUFU mutations: A case series

Background One of the hereditary syndromes associated with multiple early‐onset basal cell carcinomas (BCCs) is basal cell nevus syndrome (BCNS), of which a minority is caused by germline SUFU mutations. Germline SUFU mutations show a spectrum of phenotypes, of which multiple hereditary infundibulocystic basal cell carcinoma syndrome (MHIBCC) is one. Patients with MHIBCC develop multiple basaloid skin tumors from middle age onwards. Methods Three patients presenting with an MHIBCC phenotype were tested for a germline SUFU mutation. Skin biopsies were assessed by two dermatopathologists. Results Our study adds three new pathogenic SUFU variants, including a mosaic, to the current literature. Literature suggests a spectrum of phenotypes of patients carrying the same SUFU mutation, which ranges from the MHIBCC phenotype, to BCNS, to patients that develop life‐threatening brain tumors. This last risk is significantly higher in germline SUFU mutation carriers when compared to BCNS patients carrying germline PTCH1 mutations. Conclusions Germline SUFU mutation carriers should be recognized as a distinct group of patients carrying specific health risks, independent of meeting the BCNS criteria. Phenotypic prediction based on the specific SUFU mutation seems unfeasible. It is of utmost importance that the less apparent MHIBCC phenotype is recognized, to provide (second generation) germline SUFU mutation carriers appropriate healthcare.