REVIEW Tumours of familial origin in the head and neck Carlos Suáreza, b, Juan Pablo Rodrigoa, b, Alfio Ferlitoc, , , Rubén Cabanillasa, b, Ashok R. Shahad and Alessandra Rinaldoc aDepartment of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain bInstituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain cDepartment of Surgical Sciences, ENT Clinic, University of Udine, I-33100 Udine, Italy dHead and Neck Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Summary Individuals with inherited cancer syndromes are at significant risk of developing both benign and malignant tumours as a result of a germline mutation in a specific tumour suppressor gene. Tumours of familial origin are a rare event in the head and neck but despite this, they deserve a growing interest. Familial paragangliomas are most of the time limited to the paraganglionar system, but also may be part of different syndromic associations. Since early detection of paragangliomas reduces the incidence of morbidity and mortality, genotypic analysis in the search of SDHB, SDHC and SDHD mutations in families of affected patients plays a front-line diagnostic role, leading to more efficient patient management. Multiple endocrine neoplasias type 1 are characterized by the simultaneous occurrence of at least two of the three main related endocrine tumours: parathyroid, enteropancreatic and anterior pituitary. These tumours arise from inactivating germline mutations in the MEN-1 gene. No clear correlation of MEN-1 genotype with genotype has emerged to date, and MEN-1 mutation testing in tumours is not used clinically because it have not implications for tumour staging. Multiple endocrine neoplasia type 2 is due to a germline mutation in the RET proto-oncogene. Hallmarks of MEN-2A (the commonest phenotypic variant) include medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. The most central clinical difference with MEN-1 is that the associated cancer can be prevented or cured by early thyroidectomy in mutation carriers. Individuals with neurofibomatosis type 1 present early in life with pigmentary abnormalities, skinfold freckling and iris hamartomas, as result of NF1 gene mutation. Neurofibromatosis 2 is caused by inactivating mutations of the NF2 gene, and is characterized by the development of nervous system tumours (mainly bilateral vestibular schwannomas), ocular abnormalities, and skin tumours. The molecular genetic basis of nasopharyngeal carcinomas remains unknown, but there is evidence for the linkage of these tumours to chromosome 3p. Finally, the high rate of p16 mutations in squamous cell carcinomas and the association of p16 with familial melanoma propose p16 as an ideal candidate gene predisposing to familial squamous cell carcinomas. The elucidation of the cellular processes affected by dysfunction in familial tumours of the head and neck may serve to identify potential targets for future therapeutic interventions. Oral Oncology Volume 42, Issue 10 , November 2006, Pages 965-978 doi:10.1016/j.oraloncology.2006.03.002 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.