Abstract
In the Netherlands, the majority of hereditary head and neck paragangliomas (HNPGL) are caused by germline variants in the succinate dehydrogenase genes (SDHD, SDHB, SDHAF2). Here, we evaluate a four-generation family linked to a novel SDHB gene variant with the manifestation of a HNPGL. A family-based study. The VU University Medical Center (VUmc) Amsterdam, a tertiary clinic for Otolaryngology and Head and Neck Surgery. The index patients presented with an embryonic rhabdomyosarcoma and a non-Hodgkin lymphoma. Array-based comparative genomic hybridisation (aCGH) analysis and multiplex ligation-dependent probe amplification (MLPA) revealed a novel deletion of exon 1-3 in the SDHB gene, suspected to predispose to paraganglioma (PGL)/pheochromocytoma (PHEO) syndrome type 4. Subsequently, genetic counselling and DNA testing were offered to all family members at risk. Individuals that tested positive for this novel SDHB gene variant were counselled and additional clinical evaluation was offered for the identification of HNPGL and/or PHEO. The DNA of 18 family members was tested, resulting in the identification of 10 carriers of the exon 1-3 deletion in the SDHB gene. One carrier was diagnosed with a carotid body PGL and serum catecholamine excess, which was surgically excised. Negative SDHB immunostaining of the carotid body tumour confirmed that it was caused by the SDHB variant. The remaining 9 carriers showed no evidence of PGL/PHEO. Deletion of exon 1-3 in the SDHB gene is a novel germline variant associated with the formation of hereditary HNPGL.
Highlights
Paragangliomas (PGLs) are rare, highly vascularised, usually benign neoplasms of paraganglia, neuroendocrine organs derived from neural crest chromaffin cells
Individuals that tested positive for this novel SDHB gene variant were counselled and additional clinical evaluation was offered for the identification of head and neck paragangliomas (HNPGL) and/or PHEO
SDHB immunostaining of the rhabdomyosarcoma and non-Hodgkin lymphoma showed that there was no causal relationship between the SDHB gene variant and these tumours, this novel exon deletion was suspected to predispose to PGL/PHEO syndrome type 4 based on the characteristics of the gene variant itself
Summary
In the Netherlands, the majority of hereditary head and neck paragangliomas (HNPGL) are caused by germline variants in the succinate dehydrogenase genes (SDHD, SDHB, SDHAF2). Array-based comparative genomic hybridisation (aCGH) analysis and multiplex ligation-dependent probe amplification (MLPA) revealed a novel deletion of exon [1-3] in the SDHB gene, suspected to predispose to paraganglioma (PGL)/pheochromocytoma (PHEO) syndrome type 4. Individuals that tested positive for this novel SDHB gene variant were counselled and additional clinical evaluation was offered for the identification of HNPGL and/or PHEO. Results: The DNA of 18 family members was tested, resulting in the identification of 10 carriers of the exon [1-3] deletion in the SDHB gene. Conclusion: Deletion of exon [1-3] in the SDHB gene is a novel germline variant associated with the formation of hereditary HNPGL
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Schedule a callMore From: Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery
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