Main features of tuberous sclerosis complex
What are the main characteristics of the tuberous sclerosis complex (TSC)?
TSC is an inherited disorder that affects 1:6000 newborns and is characterized by the potential for hamartoma formation in several organs, including the brain, heart, skin, eyes, kidney, lungs, liver, and gastrointestinal tract. Its inheritance is autosomal dominant with almost complete penetrance and is caused by mutations in the TSC1 (chromosome 9q34) or TSC2 (chromosome 16p13.3) genes, which encode the tumor suppressor proteins hamartin and tuberin, respectively . TSC2 and PKD1 genes are in close relationship and lie adjacent to each other on chromosome 16 at 16p13.3. Deletions inactivating TSC2 and PKD1 are associated with polycystic kidneys diagnosed during the first year of life or early childhood, also known as TSC2/PKD1 contiguous gene syndrome. Therefore TSC should be considered in children with kidney cysts and no family history of PKD.
A definite diagnosis of TSC includes at least two major features (renal angiomyolipoma [AML], facial angiofibromas or forehead plaques, nontraumatic ungual or periungual fibroma, three or more hypomelanotic macules, shagreen patch, multiple retinal nodular hamartomas, cortical tuber, subependymal nodule, subependymal giant cell astrocytoma, cardiac rhabdomyoma, lymphangioleiomyomatosis) or one major feature plus two minor features (multiple kidney cysts, nonrenal hamartoma, hamartomatous rectal polyps, retinal achromic patch, cerebral white matter radial migration tracts, bone cysts, gingival fibromas, “confetti” skin lesions, multiple enamel pits).
Kidney manifestations, present in 50% to 80% of patients, include multiple AMLs, kidney cysts, and rarely (2% to 3%) RCCs. AMLs are the most common benign tumors of the kidney and are composed of abnormal vessels, immature smooth muscle cells, and fat cells. These tumors are the second most common cause of retroperitoneal hemorrhage, and they may also cause clinical problems secondary to compression and replacement of kidney tissue, leading to ESKD. Patients suffering from contiguous gene syndrome commonly develop ESKD at an earlier age compared with those with ADPKD alone. Genetic testing for TSC1 and TSC2 is clinically available.
