PKD1 Variants of Uncertain Significance Found in a 64 year-old Male With Simple Renal Cysts and Thoracic Aortic Disease




Tatapudi, Suhas V.V.


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Introduction: Thoracic aortic disease (TAD) - aneurysms and dissections, is a clinically silent disorder caused by weakening of major blood vessels which may lead to rupture and imminent mortality. Simple renal cysts are relatively common and are associated with numerous etiologies. Case presentation: Here we present the case of a 64 year-old male with a history of smoking, hypertension, and stroke due to cerebral aneurysm. He presented with substernal chest pain and was diagnosed with a type B aortic dissection extending from the left subclavian artery to the left iliac artery. An aortic endograft was placed to prevent rupture, covering the ostium of the left subclavian artery. Immediate post-operative bilateral lower extremity paraplegia developed, ultimately necessitating a subclavian artery bypass for resolution. Despite clinical improvement, two weeks post-operatively an aortic rupture occurred, leading to cardiac arrest and demise. Pathologic and Ancillary findings: Notable findings on autopsy included aortic dissection and rupture, left hemothorax, multicystic kidneys, and prior evidence of craniotomy. The dissection extended anterograde to left internal iliac artery and retrograde to the sinotubular junction with rupture just distal to the distal aspect of the endograft. No abnormalities were reported in aortopathy panels. Polycystic kidney disease panels revealed three variants of uncertain significance (VUS) within the PKD1 gene: p.Val2905Ile, p.Lys3232Glu, p.Leu3477Ile. Congophilic (amyloid) angiopathy was discovered within several vessels in the brain which may be associated with the history of a cerebral aneurysm. Discussion: Hypertension and smoking are significant risk factors for systemic vascular disease. While PKD1 and PKD2 mutations can be seen associated with autosomal dominant polycystic kidney disease, heterozygous mutations may result in milder cystic disease. Through retrospective case reports and series, Ziganshin et al proposed an association between simple renal cysts and TAD. As more evidence is established, a diagnosis of simple renal cysts may prompt the need for screening for TAD. Our clinical and molecular picture may further substantiate a potential relationship between TAD, cystic renal disease, and mutations in PKD1 and PKD2 genes. Furthermore, genetic counseling may also be necessary for surviving family members. This case exemplifies the importance of postmortem autopsies and the discovery of genetic variants with potential clinical implication.