OMIM ID:
Danon Disease
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
The ocular features of Danon disease are less well known than the systemic manifestations and are as yet not fully delineated likely because not all patients have visual symptoms or fundus changes. The most commonly described fundus abnormalities are pigmentary changes variously called a peripheral pigmentary retinopathy or a pigmentary atrophy in some cases. Changes in pigmentation may be mild in both affected males and carrier females, but are generally more severe in males. A bulls-eye maculopathy and color vision deficiencies have been described. Loss of visual acuity is variable and may lead to symptoms before myopathy is evident. Vision loss is usually progressive and may be reduced to hand motions. OCT shows thinning of the photoreceptor and RPE layers. The full field ERG is reduced in amplitude consistent with a generalized cone-rod dystrophy.
Systemic Features
This disorder, originally believed to be a type of glycogen storage disease, is actually a form of autophagic vacuolar myopathy. The characteristic vacuoles are found in muscle cytoplasm surrounded by sarcolemmal proteins and basal lamina. The primary extraocular disease occurs in the myocardium although skeletal muscle may also be involved. Intellectual disability is a variable and inconsistent feature.
Cardiac rhythm abnormalities are common and include AV nodal block, atrial fibrillation, and Wolff-Parkinson-White EKG findings. Hypertrophic cardiomyopathy (and sometimes dilated cardiomyopathy) with primary involvement of the left ventricle is common. Symptoms typically occur in males before the age of 20 years and somewhat later in females.
Some patients have muscular weakness and exercise intolerance. Diagnosis can be made when the characteristic vacuoles are present in a muscle biopsy but their absence does not rule out the diagnosis.
Genetics
Inheritance
This is an X-linked dominant disorder caused by mutations in LAMP2 (Xp24). Females are generally less severely affected than males. Most men with Danon disease have some intellectual disability as well as skeletal myopathy but these features are found in less than half of affected women.
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.