Danon Disease Clinical Presentation

Updated: Nov 24, 2021
  • Author: Keith K Vaux, MD; Chief Editor: Maria Descartes, MD  more...
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Danon disease usually manifests with the clinical triad of cardiomyopathy, skeletal myopathy, and intellectual disability. [4, 5, 6] The skeletal myopathy and intellectual disability 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. [11] 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 [26]

    • Male patients may present with palpitations or documented arrhythmias, syncope, chest pain, or cardiac arrest. [2, 11, 10, 1, 8]

    • Female patients most typically present more with symptoms of dilated cardiomyopathy and CHF. [11, 4]

  • 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. [4]

    • Most male patients have intellectual disability or a learning disorder. [4, 8, 12]

    • Some male patients present with neurologic symptoms in infancy, including difficulties in walking and delay in achieving developmental milestones. [2, 9]

    • Spinazzi reported 3 patients that had cardioembolic strokes. All 3 patients had a history of atrial fibrillation. [27]



See the list below:

  • Cardiac findings [26]

    • Heart murmurs can be noted upon examination. However, cardiac findings may be normal. [2, 7]

    • 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 kneecaps) 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. [4]

    • Peripheral neuropathy and maculopathy were reported in one patient with Danon syndrome. [15]

    • Cerebellar and cranial-nerve problems have not been reported.

  • Ophthalmologic findings

    • Males

      • Moderate loss of central visual acuity

      • Depigmentation of the peripheral retina [8]

      • Decreased visual acuity with diffuse choriocapillary atrophy [9]

    • Females [12]

      • 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, 7, 4]



The transmission of Danon disease is often X-linked dominant; however, spontaneous mutations have been documented. [1] Phenotypic expression varies. [10]