OMIM ID:
Wilson Disease
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
The cornea and lens have visible copper deposition. This is responsible for the classic (though non-pathognomonic) copper-colored Kayser-Fleischer ring in the cornea where evidence of copper deposition can be visualized in the posterior stroma and in the endothelium. About 50-60% of patients at any point have evidence of such copper deposition but the number rises to 90% in patients with neurologic and psychiatric symptoms. Copper deposition in the lens leads to a ‘sunflower’ or 'sunburst' cataract consisting of a greenish central disc in the anterior capsule with spoke-like radial cortical opacities. Eye involvement in Wilson disease usually does not lead to significant impairment of vision.
Systemic Features
This is a disorder of copper metabolism. It is associated with severe liver disease, often beginning with signs of recurrent jaundice, sometimes a hepatitis-like illness, and often culminating in liver failure. Hepatobiliary malignancies are a significant risk, occurring in more than 1 percent of patients. Neurologic toxicity leads to various movement disorders such as tremors, poor coordination, dystonia, and choreoathetosis. Many patients have mental symptoms such as depression, neurotic behavior, and personality disturbances. Some have a mask-like facies and pseudobulbar symptoms. Symptoms can appear anytime from 3 years of age to over 50. Other organs such as kidney, pancreas, heart and even joints may also be involved.
Patients often have a low serum ceruloplasmin, low copper levels, increased urinary excretion of copper, and increased concentration of copper in the liver.
Genetics
Inheritance
This is an autosomal recessive disorder caused by homozygous or doubly heterozygous mutations in the ATP7B gene (13q14.3). Heterozygotes usually do not develop symptoms but may have reduced serum ceruloplasmin levels.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.