<unk>  is an autosomal dominant<unk>  disorder. This means that a patient with<unk>  has a 50% chance of transmitting this disorder to his or her children. Most individuals with<unk>  have a parent who also has the condition, however, approximately 10% -20% of individuals with<unk>  have the condition as a result of a spontaneous mutation and are thus the first person in their family to be affected.<unk>  has thus far been linked with mutations in three genes: *<unk> 1 which maps to chromosome 8q24.1 *<unk> 2 which maps to 11p13 *<unk> 3 which maps to the short arm of Chromosome 19 (though its exact location has yet to be precisely determined) Mutations in these genes typically lead to the synthesis of a truncated<unk>  protein which does not function normally. It is known that<unk>  proteins are important enzymes in the synthesis of heparan sulfate; however the exact mechanism by which altered synthesis of heparan sulfate that could lead to the abnormal bone growth associated with<unk>  is unclear. It is thought that normal chondrocyte proliferation and differentiation may be affected, leading to abnormal bone growth. Since the<unk>  genes are involved in the synthesis of a glycan (heparan sulfate),<unk>  may be considered a congenital disorder of glycosylation according to the new CDG nomenclature suggested in 2009. For individuals with<unk>  who are considering starting a family, preimplantation genetic testing and prenatal diagnosis are available to determine if their unborn child has inherited the disease.<unk>  has a 96% penetrance, which means that if the affected gene is indeed transmitted to a child, the child will have a 96% of actually manifesting the disease, and 4% chance of having the disease but never manifesting it. The 96% penetrance figure comes from only one study. Other studies have observed both incomplete and variable penetrance but without calculating the % penetrance, e.g. In both the aforementioned studies the symptomless individuals carrying the faulty gene were predominantly female, leading to speculation that incomplete penetrance is more likely to be exhibited in females. Indeed, other work has shown that boys/men tend to have worse disease than females, as well as that the number of<unk>  in affected members of the same family can vary greatly. It is also possible for females to be severely affected. Severity of symptoms varies between individuals, even in the same family. Symptoms are more likely to be severe if the mutation is on the<unk> 1 gene rather than<unk> 2 or<unk> 3;<unk> 1 is also the most commonly affected gene in patients of this disorder.
Hereditary multiple exostoses
Inherited patterned lentiginosis
Diffuse idiopathic skeletal hyperostosis
Pycnodysostosis
Familial myxovascular fibromas
Nevoid basal-cell carcinoma syndrome
Gerodermia osteodysplastica
Acrofrontofacionasal dysostosis