MP152TUBEROUS SCLEROSIS COMPLEX: RENAL AND EXTRA-RENAL MANIFESTATIONS

Abstract

INTRODUCTION AND AIMS: Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder, caused by mutations in TSC1 or TSC2 genes. It is associated with hamartomas or benign tumor growths in the brain, heart, lung, eye, or kidney. There is great phenotypic variability between individuals, even across families. The purpose of this study was to review the renal and extra-renal manifestations of patients followed in a Nephrology consult, adult and paediatric, in our hospital. METHODS: We have a follow up of 10 patients with tuberous sclerosis complex in Nephrology consult, 50% males, with a mean age of 23.2±11 years. RESULTS: Neurological manifestations were present at diagnosis in 90% of patients, and mean age at onset was 8.2±11 years. Only 30% of patients had family history, and genetic study was performed and was positive in four patients, two patients with TSC2 mutation, one with TSC1 mutation and one with contiguous gene syndrome (mutation of TSC2/PKD1). The most common renal manifestation was angiomyolipoma, present in 80% of patients, and developed in most cases in the second decade of life. One patient was submitted to total nephrectomy due to angiomyolipoma haemorrage. Renal cell carcinoma was diagnosed in 20% of patients. One patient had bilateral renal cell carcinoma, was submitted to bilateral nephrectomy and started haemodialysis at age 37, he was submitted to a renal transplant at age 43. Of these patients all have extra-renal manifestations. All patients had neurological involvement, namely, cortical and subcortical tubers in 8 patients, subependymal giant cell astrocytoma in 5 patients, epilepsy in 6 patients, and cognitive impairment in 3 patients. Cutaneous manifestations were focal hypopigmentation changes in 7 patients, and facial angiofibromas in 2 patients. Retinal astrocytic hamartomas were present in 4 patients. One patient had a cardiac rhabdomyoma. One patient had a hepatic haemangioma. One patient had a papillary thyroid cancer. Fifty percent of patients were treated with mTOR inhibitor, sirolimus or everolimus, for size reduction of subependymal giant cell astrocytoma and/or angiomyolipomas. CONCLUSIONS: The care of TSC patients has improved over the past decade due to the introduction of mTOR inhibitors for the treatment of many manifestations of TSC. Clinical manifestations are widely variable, thus the importance of a timely multidisciplinary approach is essential to diminish the impact of this disease. Nephrological follow up plays a central role as renal involvement is a major cause of morbidity and mortality in TSC.