Characteristics of cardiomyopathy in Alström syndrome: Prospective single-center data on 38 patients

Abstract

Background: Alström syndrome (AS) is a rare monogenetic disorder with multi-organ involvement. Complex metabolic disturbances are common and cardiomyopathy is a well-recognized feature in infants as well as in older children and adults. Although the mechanism of cardiomyopathy is not known, previous reports suggest that individuals with infantile-onset cardiac disease recover completely.

Methods: In this single center prospective series of 38 children and adults (age range 1.7 to 37.9years; 20 females) with AS, we evaluated cardiac manifestations in detail, in the context of specific ALMS1 mutations and multisystem involvement. All patients underwent ALMS1 sequencing, biochemical testing, electrocardiogram, and echocardiographic imaging with speckle tracking to evaluate systolic strain; 21 patients underwent cardiac magnetic resonance imaging with T1 mapping.

Results: Approximately half of patients (17/38) had a previous diagnosis of cardiomyopathy. Global longitudinal strain, a measure of systolic contractile function, was abnormal in 94% of patients and correlated with body mass index (r=0.602, p=0.002) and C-reactive protein level (r=0.56, p=0.004), but only in children. Electrocardiographic abnormalities were seen in two-thirds of patients, and left ventricular dilatation and/or dysfunction was present in 4 adults and 4 children.

Conclusion: AS patients with a history of resolved infantile cardiomyopathy continue to have residual impairment in cardiac function. For patients with a normal ejection fraction and no prior cardiac history, strain can be abnormal, suggesting subclinical cardiac involvement. Close cardiac screening and aggressive modification of other manifestations of AS that are risk factors for cardiac disease, including obesity, inflammation, diabetes and dyslipidemia, are essential in caring for patients with AS.

Keywords: Alström; Cardiomyopathy; Echocardiography; MRI; Strain imaging.

Fig. 1

Example of strain imaging in the apical four-chamber echo view (left panel) of a 19 year old AS patient with a normal LV ejection fraction of 61%. Time vs longitudinal strain curves (right panel) show strain (top), strain rate (middle), and the ECG for one cardiac cycle. The LV global longitudinal strain was abnormal at −14% and was an average of the six colored segments shown as well as the segments in the apical two-chamber and apical three-chamber views.

Fig. 2

19 Year-old male with AS. Late gadolinium enhancement (LGE) images in the 4 chamber (left) and short axis (right) views show midwall enhancement of the interventricular septum (arrows), a finding consistent with myocardial fibrosis from a nonischemic etiology.