Alström's Syndrome and the Heart

Dr C Carey Consultant Cardiologist
Torbay Hospital, Devon, UK

Although Alström's Syndrome was first described in 1959, the association with dilated cardiomyopathy (DCM) was recognised only 7 years ago. Yet we now know that cardiac failure affects at least 65% of patients at some stage in their lives, that cardiomyopathy is a major feature of Alström's, and that cardiac problems are the commonest cause of early death.

For around 50% of Alström patients the onset of sudden, severe, heart failure at around two months of age is the first manifestation of the syndrome. Many of these infants survive the acute episode, making a full clinical and echo recovery. Unfortunately an increasing proportion of the survivors develop progressive cardiomyopathy later in adolescence or adulthood.

A further group of Alström patients, who have no history of cardiac dysfunction in infancy, develop progressive dilated cardiomyopathy for the first time in teenage or adult life. Mortality in all patients with progressive DCM is high, at around 50%.

We do not yet know whether the onset of cardiomyopathy is preceded by sub-clinical disease in infants or adults, nor do we know the mechanism of recovery in the infantile form. In infants endomyocardial fibrosis is described, while in adults thick bands of fibrous tissue are seen on myocardial samples at autopsy.

The remaining Alström patients show no signs of cardiac failure to date, but many are young and a number may develop DCM in the future.

Typically, Alström's Syndrome is diagnosed relatively late, because it is rare and the cardinal features emerge slowly. Earlier diagnosis is possible if Alström's is considered routinely in the differential diagnosis of infants with cardiomyopathy, as this often precedes the eye signs. Similarly, the association of nystagmus and/or photophobia in an infant with a history of cardiomyopathy indicates a significant possibility of Alström's Syndrome.

Once the diagnosis of Alström's is established, patients need lifelong monitoring for the development of DCM. Based on our data so far, we would make the following suggestions:

• Those with infantile cardiomyopathy will naturally be followed according to clinical need.
However, even if the child appears to recover fully, there is a role for ECG and echo monitoring because of the risk of recurrence in the early/mid teens.

• In unaffected patients, a yearly clinical history, examination and ECG are suggested. In addition, we suggest an Echocardiogram in infancy, age 5 and 10 years and then at 2-year intervals throughout the teens. Interim Echos are indicated at any time if new ECG changes are seen or if there are symptoms suspicious of left ventricular dysfunction.

We review these recommendations regularly as we learn more about the natural history of Alström's cardiomyopathy. We hope our strategy will permit more timely introduction of heart failure management strategies such as angiotensin-converting-enzyme inhibitors, beta-blockade, digoxin, and diuretics.

Finally, the interaction of the heart with other aspects of Alström's must not be forgotten. For example, glitazones are an exciting approach to management of insulin resistance, but are contraindicated in cardiac failure. Use of amiodarone for atrial fibrillation suppression appears to have a high risk of inducing thyroid problems, whilst ACE inhibitors and spironolactone need to be used with care in renal impairment. Interestingly, despite the mixed hyperlipidaemia coronary artery disease has not yet been described.