TY - JOUR
T1 - Characteristics of cardiomyopathy in Alström syndrome
T2 - Prospective single-center data on 38 patients
AU - Brofferio, Alessandra
AU - Sachdev, Vandana
AU - Hannoush, Hwaida
AU - Marshall, Jan D.
AU - Naggert, Jürgen K.
AU - Sidenko, Stanislav
AU - Noreuil, Anna
AU - Sirajuddin, Arlene
AU - Bryant, Joy
AU - Han, Joan C.
AU - Arai, Andrew E.
AU - Gahl, William A.
AU - Gunay-Aygun, Meral
N1 - Publisher Copyright:
© 2017
PY - 2017/8
Y1 - 2017/8
N2 - 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 37.9 years; 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.
AB - 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 37.9 years; 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.
KW - Alström
KW - Cardiomyopathy
KW - Echocardiography
KW - MRI
KW - Strain imaging
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U2 - 10.1016/j.ymgme.2017.05.017
DO - 10.1016/j.ymgme.2017.05.017
M3 - Article
C2 - 28610912
AN - SCOPUS:85020453168
SN - 1096-7192
VL - 121
SP - 336
EP - 343
JO - Molecular genetics and metabolism
JF - Molecular genetics and metabolism
IS - 4
ER -