Danon Disease
Patient Information
Characteristics
Background and History
This disorder was first described by M.J. Danon and coworkers in 1981. It was originally thought to be a form of glycogen storage disease of which there are multiple types but it has since been shown to be a disease of abnormal metabolism of breakdown products of tissue.
Clinical Correlations
Both males and females are affected but the condition generally has an earlier onset and is more severe in males. Signs and symptoms are highly variable but often have their onset in the second or third decade of life. In some patients the first symptoms are that of visual difficulties such as blurred vision or alterations of color perception. These can progress to legal blindness later in life. In other patients, muscle weakness beginning with the arms and shoulders is the first symptom. In yet others, heart disease with abnormal rhythm, palpitations, and shortness of breath may be the first symptoms of this disorder. Enlargement of the heart and irregular rhythms can be life-threatening.
Some degree of intellectual disability is present in most males but in less than half of females.
Genetics
Inheritance
This is an X-linked dominant disease in which both sexes are affected. A mutation on the X-chromosome is responsible. Both males and females can pass on the mutation to their children, but since males have only one X-chromosome which they obligatorily transmit to their daughters (their Y-chromosome is passed to their sons), all their daughters and none of their sons will inherit Danon disease. Half of all children of both sexes born to affected mothers will inherit this condition.
Pedigree
X-linked dominant, father affected
X-linked inheritance patterns result when disease-causing mutations are located on the X chromosome. Males have one X chromosome while females have two. A mutation on the male's X chromosome frequently is lethal or renders him unable to reproduce. However, in rare cases when males have children, they can expect that all of then will inherit the condition.
X-linked inheritance patterns result when disease-causing mutations are located on the X chromosome. Males have one X chromosome while females have two. A mutation on the male's X chromosome frequently is lethal or at least renders them unable to reproduce. However, in rare cases when males have children, they can expect that all of then will inherit the condition.
X-linked dominant, mother affected
X-linked inheritance patterns result from mutations located on the X chromosome. Females have two X chromosomes of which only one carries a mutation in X-linked dominant disorders. This usually results in expression of the disease and women with a single mutation have the disorder caused by the mutation. Half of their offspring, male and female, will inherit the mutation. Men, with only one X chromosome, will always have the condition if they inherit the one with the mutation. Men would transmit it to all of their offspring. Without a modifying normal gene on a second X chromosome, X-linked dominant conditions are frequently lethal in such males. The result is a vertical transmission pattern, usually from female to female.
X-linked inheritance patterns result from mutations located on the X chromosome. Females have two X chromosomes of which only one carries a mutation in X-linked dominant disorders. This usually results in expression of the disease and women with a single mutation have the disorder caused by the mutation. Half of their offspring, male and female, will inherit the mutation. Men, with only one X chromosome, will always have the condition if they inherit the one with the mutation. Men would transmit it to all of their offspring. Without a modifying normal gene on a second X chromosome, X-linked dominant conditions are frequently lethal in such males. The result is a vertical transmission pattern, usually from female to female.
Diagnosis and Prognosis
The diagnosis is likely made by a cardiologist or a neurologist. However, the eye symptoms may lead to consultation with an ophthalmologist before the systemic symptoms are evident. There is no treatment for the retinal disease in the eye, but if heart symptoms become severe, a heart transplant can be life saving. Rare patients my loss their mobility and become confined to a wheelchair if the muscle weakness becomes severe enough.
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