**3. Risk factors**

As for the risk factors described, genetic predisposition of young patients with some specific genetic syndromes has been evidenced:

## **3.1 Syndromes associated with germline mutations in tumor suppressor genes**

• Sd. Li-Fraumeni (p53): autosomal dominant disorder involving a germline mutation of the p53 tumor suppressor gene. Affected individuals may suffer from breast cancers, soft-tissue sarcomas, central nervous system malignancies, leukemia, and adrenocortical carcinomas [11]

• Retinoblastoma (Rb1, 13q14 deletion) [11]. Huber et al. in a retrospective analysis of 14 patients between 1974 and 1999, reported four patients (28.6%) with this history, with an average latency of 9 years (range 3–15 years) for OSHN [12].
