Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) is a very rare hereditary disorder characterized by cutaneous leiomyomas (CLMs), uterine leiomyomas (ULMs), renal cysts (RCys) and renal cell cancers (RCCs). We aimed to describe the genetics, clinical features and potential genotype-phenotype associations in the largest cohort of fumarate hydratase enzyme mutation carriers known from Spain using a multicentre, retrospective study of individuals with a genetic or clinical diagnosis of HLRCC. We collected clinical information from medical records, analysed genetic variants and looked for genotype-phenotype associations. Analyses were performed using R 3.6.0. software. We included 197 individuals: 74 index cases and 123 relatives. CLMs were diagnosed in 65% of patients, ULMs in 90% of women, RCys in 37% and RCC in 10.9%. Twenty-seven different pathogenic variants were detected, 12 (44%) of them not reported previously. Patients with missense pathogenic variants showed higher frequencies of CLMs, ULMs and RCys, than those with loss-of-function variants (p = 0.0380, p = 0.0015 and p = 0.024, respectively). This is the first report of patients with HLRCC from Spain. The frequency of RCCs was lower than those reported in the previously published series. Individuals with missense pathogenic variants had higher frequencies of CLMs, ULMs and RCys.
Cancers. 2020 Nov 05*** epublish ***
A Beatriz Sánchez-Heras, Adela Castillejo, Juan D García-Díaz, Mercedes Robledo, Alexandre Teulé, Rosario Sánchez, Ángel Zúñiga, Enrique Lastra, Mercedes Durán, Gemma Llort, Carmen Yagüe, Teresa Ramon Y Cajal, Consol López San Martin, Adrià López-Fernández, Judith Balmaña, Luis Robles, José M Mesa-Latorre, Isabel Chirivella, María Fonfria, Raquel Perea Ibañez, M Isabel Castillejo, Inés Escandell, Luis Gomez, Pere Berbel, Jose Luis Soto
Cancer Genetic Counselling Unit, Medical Oncology Department, Hospital General Universitario de Elche, 03203 Elche, Spain., Molecular Genetics Unit, Hospital General Universitario de Elche, 03203 Elche, Spain., Clinical Genetics Unit, Department of Internal Medicine, University Hospital Príncipe de Asturias, 28805 Alcalá de Henares, Spain., Hereditary Endocrine Cancer Group, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain., Hereditary Cancer Program, Catalan Institute of Oncology, Instituto de Investigación Biomédica de Bellvitge, 08908 Hospitalet de Llobregat, Spain., Unidad Multidisciplinar de Enfermedades de Baja Prevalencia, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Hospital General Universitario de Alicante, 03015 Alicante, Spain., Unit of Genetics, Hospital Universitario Politécnico La Fe, 46026 Valencia, Spain., Unidad de Consejo Genético en Cáncer Hereditario, Servicio de Oncología Médica, Hospital Universitario de Burgos, 09006 Burgos, Spain., Genética del Cáncer, Instituto de Biología y Genética Molecular (IBGM-UVA-CSIC), 47003 Valladolid, Spain., Hereditary Cancer Unit, Medical Oncology Department, Corporació Sanitaria Universitària Parc Taulí, 08208 Sabadell, Spain., Hereditary Cancer Unit, Medical Oncology Department, Consorci Sanitari de Terrassa, 08191 Rubi, Spain., Medical Oncology Department, Hospital Santa Creu i Sant Pau, 08091 Barcelona, Spain., Hereditary Cancer Genetics Group, Medical Oncology Department (VHIO), Hospital Universitario Vall d'Hebron, 08035 Barcelona, Spain., Unidad de Cáncer Familiar, Servicio de Oncología Médica, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain., Department of Medical Oncology, INCLIVA Biomedical Research Institute, University of Valencia, 46010 Valencia, Spain., Cancer Genetic Counselling Unit, Medical Oncology Department, Consorcio Hospitalario Provincial de Castellón, 12002 Castellón, Spain., Servicio de Dermatología, Hospital General Universitario de Elda, 03600 Elda, Spain., Urology Department, Hospital Universitario Sant Joan de Alicante, 03550 Sant Joan de Alicante, Spain., Departamento de Histología y Anatomía, Facultad de Medicina, Universidad Miguel Hernández, 03550 Sant Joan de Alicante, Spain.