The Genetic Background of Head and Neck Paragangliomas

Familial paraganglioma of the head and neck (HNP) has been a known entity for decades. Publications in 2000 and 2001 showed that mutations of the genes encoding the succinate dehydrogenase subunits B, C, and D, SDHB, SDHC, and SDHD, predispose to paraganglioma syndromes type 4, 3, and 1, respectively (PGL 1, PGL 3, PGL 4). PGL 1 tumors occurred only in offspring who inherited the mutation from the father, whereas PGL 3 and 4 are transmitted autosomal dominantly. We have established a national registry which was extended by cases from other countries for HNP in order to study the prevalence and clinical spectrum of SDHB, SDHC, and SDHD mutation carriers.

On December 31, 2004, the International HNP Registry based in Freiburg contained 121 (96 German, 10 Polish, 7 Italian, 5 French, 1 each Finnish, Swiss, Spanish) unrelated index cases. Prevalences were as follows: for SDHB, 7% (n = 8; 5 German and 3 international); for SDHC, 4% (n = 5; 2 and 3); for SDHD, 17% (n = 20; 11 and 9 carriers, respectively). The spectrum of PGL 1, 3, and 4 was studied, including 16 relatives with mutations. Malignant paraganglioma was seen in 4/9 carriers of SDHB mutations but in none of the other groups. Multifocal HNP occurred in 1/9 SDHB, 0/6 SDHC, and 16/32 SDHD mutation carriers and 9/89 cases with sporadic HNP. Abdominal or thoracic pheochromocytoma developed in 1 SDHB and 8 SDHD, but not in SDHC, mutation carriers.

In conclusion, otolaryngeology is an important discipline for endocrine tumors of the autonomic nervous system. Patients with HNP should be tested genetically for PGL 1, 3, and 4. Adequate follow-up recommendations need to be structured. Further efforts are needed to identify the gene for PGL 2.

^*For the German and International Paraganglioma Registry.