Kourosh Hayatigolkhatini - Academic Unit of Medical Genetics and Pathology, School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK
Alisha Aman - Academic Unit of Medical Genetics and Pathology, School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK
Thabo Michael Yates - Academic Unit of Medical Genetics and Pathology, School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK
Poondi Krishnan - Academic Unit of Medical Genetics and Pathology, School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, UK

Case presentation: Luke, 33 years of age, was referred to genetics because of a previously diagnosedloss of hearing in his right ear due to a glomus jugulare tumor. The referral was further supported witha family history of general cardiac enlargement and a large pheochromocytoma of the left adrenalgland in Luke’s paternal grandfather, David. Luke’s wife Katy, his two children and his siblings allappear to be healthy and there is no known consanguinity on either side of the family.Luke and his wife were also concerned about the risk of developing Alzheimer’s for Katy. There was aprevious diagnosed case of Alzheimer’s in Katy’s mother, Vera, who died from pulmonary embolismat age 66 years. Katy also has a family history of dementia that was present in her maternal grandfatherand possibly in her maternal aunt.Methods: Familial Phaeochromocytomas and Paragangliomas 4 Genes Panel (UK Genetic TestingNetwork, 2016a) was undertaken, covering the SDHB, SDHC, SDHD and VHL genes.Results: A substitution of c.274G> T in the SDHD in the heterozygous state was detected. This leads tothe p.Asp92Tyr in exon 3 of SDHD. According to the NCBI ClinVar (2016) database the variant wasfound to be pathogenic.Conclusion: The consultand, tested positive for the pathogenic variant within the SDHD gene, leadingto a diagnosis of PGL1. The presence of this familial pathogenic variant was confirmed followingcascade testing of the relatives.Following Katy’s concern of developing Alzheimer’s (due to family history), Katy would be advised toavoid testing for any pathogenic variant associated with Alzheimer’s, since the results would beinconclusive and would only serve to increase anxiety. In turn, the risk of her children developingAlzheimer’s later in life is also low.

Pheochromocytoma, Paraganglioma, PGL1, SDHD, Alzheimer’s