Danon Disease Clinical Presentation

Updated: Feb 09, 2016
  • Author: Keith K Vaux, MD; Chief Editor: Maria Descartes, MD  more...
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Presentation

History

Danon disease usually manifests with the clinical triad of cardiomyopathy, skeletal myopathy, and mental retardation. [5] The skeletal myopathy and mental retardation are less common in females than in males. Regardless of sex, cardiomyopathy can present as a result of symptoms or congestive heart failure (CHF) or an arrhythmia-related event, such as syncope or sudden death. [13] Patients are also newly identified when asymptomatic relatives of patients with established Danon disease are evaluated and are found to have the disease.

  • Specific cardiac symptoms
    • Male patients may present with palpitations or documented arrhythmias, syncope, chest pain, or cardiac arrest. [2, 13, 9, 1, 11]
    • Female patients most typically present more with symptoms of dilated cardiomyopathy and CHF. [13, 5]
  • Specific neurologic symptoms
    • Male patients with Danon disease have weakness of the proximal extremities and neck muscles in the pattern of a limb-girdle muscular dystrophy. The weakness slowly progresses over time but can remain stable.
    • Female patients have relatively little difficulty with weakness or none at all. [5]
    • Most male patients have mental retardation or a learning disorder. [5, 11, 17]
    • Some male patients present with neurologic symptoms in infancy, including difficulties in walking and delay in achieving developmental milestones. [2, 14]
    • Spinazzi reported 3 patients that had cardioembolic strokes. All 3 patients had a history of atrial fibrillation. [18]
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Physical

See the list below:

  • Cardiac findings
    • Heart murmurs can be noted upon examination. However, cardiac findings may be normal. [2, 12]
    • With advanced disease, signs of CHF (eg, dyspnea upon exertion, decreased exercise tolerance) can occur.
    • In addition, signs of poor cardiac output (eg, poor capillary refill in the extremities or knee caps) can be seen.
    • Signs of CHF are often seen in female patients upon initial presentation.
  • Neurologic findings
    • Male patients with Danon disease have mild weakness in the proximal extremities and neck muscles in a pattern of limb-girdle muscular dystrophy. As the muscles weaken, the deep tendon reflexes diminish, and, in rare cases, muscular atrophy is seen. [5]
    • Peripheral neuropathy and maculopathy were reported in one patient with Danon syndrome. [19]
    • Cerebellar and cranial-nerve problems have not been reported.
  • Ophthalmologic findings
    • Males
      • Moderate loss of central visual acuity
      • Depigmentation of the peripheral retina [11]
      • Decreased visual acuity with diffuse choriocapillary atrophy [14]
    • Females [17]
      • Peripheral pigmentary retinopathy
      • Lamellar opacities in the lens
      • Nonspecific changes on electroretinography
  • Other findings: Hepatomegaly and splenomegaly, as well as foot deformities, were reported in several patients. [2, 12, 5]
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Causes

The transmission of Danon disease is often X-linked dominant; however, spontaneous mutations have been documented. [1] Phenotypic expression varies. [9]

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