<unk>  is inherited in an autosomal dominant fashion.<unk>  is a genetic disorder with an autosomal dominant pattern of inheritance, variable expressivity, and incomplete penetrance. Two-thirds of<unk>  cases result from sporadic genetic mutations, not inheritance, but their offspring may inherit it from them. Current genetic tests have difficulty locating the mutation in roughly 20% of individuals diagnosed with the disease. So far, it has been mapped to two genetic loci,<unk> 1 and<unk> 2.<unk> 1 encodes for the protein hamartin, is located on chromosome 9 q34, and was discovered in 1997.<unk> 2 encodes for the protein tuberin, is located on chromosome 16 p13.3, and was discovered in 1993.<unk> 2 is contiguous with PKD1, the gene involved in one form of polycystic kidney disease (PKD). Gross deletions affecting both genes may account for the 2% of individuals with<unk>  who also develop polycystic kidney disease in childhood.<unk> 2 has been associated with a more severe form of<unk> . However, the difference is subtle and cannot be used to identify the mutation clinically. Estimates of the proportion of<unk>  caused by<unk> 2 range from 55% to 90%.<unk> 1 and<unk> 2 are both tumor suppressor genes that function according to Knudson's "two hit" hypothesis. That is, a second random mutation must occur before a tumor can develop. This explains why, despite its high penetrance,<unk>  has wide expressivity.
Tuberous sclerosis
Sugarman syndrome
Krabbe disease
Neurofibromatosis
Neurofibromatosis type 4
Neurofibromatosis type I
Neurofibromatosis type II
Leschke syndrome