Genes and the Kidney in Tuberous Sclerosis
Tuberous Sclerosis Complex / Posted 2 years ago
Tuberous sclerosis (TSC) is a rare, genetic condition that causes benign growths to occur in various body organs, particularly the brain, skin, kidney and heart. Other features of tuberous sclerosis include kidney (renal) cysts, seizures and intellectual impairment.
Two causative genes have been identified, TSC1 and TSC2. Adjacent to TSC2 on chromosome 16, lies the gene PKD1. This gene is responsible for 85% of Autosomal Dominant Polycystic Kidney Disease, a genetic condition that causes multiple renal cysts to occur, usually in adulthood.
Renal cysts are a well recognised feature of tuberous sclerosis. There is a small subgroup of patients with tuberous sclerosis who have a more severe form of renal cystic disease, often with early or congenital onset. A gene deletion involving both TSC2 and PKD1 was described in 1994, known as the TSC2/PKD1 contiguous gene deletion syndrome.
Little is known about the natural history of TSC2/PKD1 contiguous gene deletion syndrome. The largest series to date was reported in 1997 and suggested likely progression to end stage renal failure by late childhood/early adulthood. However, only three patients were over 18 years old at the time of the study.
Many more patients with contiguous gene deletions have been identified over the last ten years through the Institute of Medical Genetics’ molecular genetic diagnostic service for tuberous sclerosis and other UK genetic centres. We aim to determine the natural history of renal disease by a follow up study of these patients. This will provide important prognostic information for patients at diagnosis and help guide their management.