PKD1/TSC2 contiguous gene deletion syndrome

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A 37‐year‐old female renal allograft recipient underwent an ultrasonogram for non‐specific urinary symptoms and was found to have a solid lesion in her left native kidney suspicious for renal cell carcinoma (RCC). She was diagnosed with polycystic kidney disease (PKD) at 16 years, commenced dialysis at 30, underwent a renal transplantation at 33 and had been otherwise well. She also had attention deficit hyperkinetic disorder (ADHD) and congenial scoliosis (CS). A MR scan (MRI) of the kidneys confirmed multiple bilateral solid lesions and enlarged cystic kidneys.
As malignancy is uncommon with PKD, detailed analysis was performed to rule out Von Hippel‐Lindau disease (VHL), well known to have renal cysts and RCC. MRI of the brain surprisingly revealed cortical tubers and calcified subependymoma (Fig. 1a and b), features of tuberous sclerosis (TSC). Closer examination revealed subtle adenoma sebaceum (AS). Morphological and histopathological assessment of the nephrectomised specimen confirmed PKD with multiple angiomyolipoma (AML) without any evidence of RCC (Fig. 1c and d). Given the combined features of PKD and TSC, a diagnosis of PKD1/TSC2 contiguous gene deletion syndrome was made.
Clinical features of TSC are variable, neuropsychiatric disorders (TAND) and skin problems (AS, confetti lesions, shagreen patch) predominate. A wide array of clinical manifestations can develop (AML, cardiac rhabdomyosarcoma).1 A high index of clinical suspicion is needed to correlate atypical presentations as was seen in this subject (ADHD, CS). Solid lesions in TSC are predominantly AML but RCC may occur. TSC cysts are not as numerous as PKD cysts, and kidneys are not considerably enlarged.2 VHL is also characterised by fewer cysts but have bilateral and multifocal RCC. AML has a characteristic appearance on imaging modalities due to its solid component.
Combined PKD and TSC has been reported – PKD1/TSC2 contiguous gene deletion syndrome – as PKD1 and TSC2 genes are located on chromosome16p tail‐to‐tail and can be deleted together. This condition is characterised by early onset PKD, subtle clinical manifestations and late TSC diagnosis.3 AML is often the feature that raises a clinical suspicion in patients otherwise considered to have PKD.
Genetic testing may be considered if clinical diagnostic criteria are not satisfied and is not mandatory for either conditions.1
Von Hippel‐Lindau disease and tuberous sclerosis should be considered as potential conditions in patients with cystic kidneys and tumours. Diagnosis of PKD1/TSC2 contiguous gene deletion syndrome helps to undertake surveillance for malignancies that occur due to TSC. Also, sirolimus/ everolimus could be considered for immunosuppression and limiting growth of AML and subependymoma.
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