Characteristics of cardiomyopathy in Alström syndrome

Prospective single-center data on 38 patients

Alessandra Brofferio, Vandana Sachdev, Hwaida Hannoush, Jan D. Marshall, Jürgen K. Naggert, Stanislav Sidenko, Anna Noreuil, Arlene Sirajuddin, Joy Bryant, Joan Han, Andrew E. Arai, William A. Gahl, Meral Gunay-Aygun

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 37.9 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.

Original languageEnglish (US)
Pages (from-to)336-343
Number of pages8
JournalMolecular Genetics and Metabolism
Volume121
Issue number4
DOIs
StatePublished - Aug 1 2017

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Cardiomyopathies
Imaging techniques
Magnetic resonance
Medical problems
Speckle
Electrocardiography
C-Reactive Protein
Screening
Heart Diseases
Testing
Dyslipidemias
Dilatation
Body Mass Index
Obesity
History
Magnetic Resonance Imaging
Inflammation
Mutation

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Cite this

Brofferio, A., Sachdev, V., Hannoush, H., Marshall, J. D., Naggert, J. K., Sidenko, S., ... Gunay-Aygun, M. (2017). Characteristics of cardiomyopathy in Alström syndrome: Prospective single-center data on 38 patients. Molecular Genetics and Metabolism, 121(4), 336-343. https://doi.org/10.1016/j.ymgme.2017.05.017

Characteristics of cardiomyopathy in Alström syndrome : Prospective single-center data on 38 patients. / Brofferio, Alessandra; Sachdev, Vandana; Hannoush, Hwaida; Marshall, Jan D.; Naggert, Jürgen K.; Sidenko, Stanislav; Noreuil, Anna; Sirajuddin, Arlene; Bryant, Joy; Han, Joan; Arai, Andrew E.; Gahl, William A.; Gunay-Aygun, Meral.

In: Molecular Genetics and Metabolism, Vol. 121, No. 4, 01.08.2017, p. 336-343.

Research output: Contribution to journalArticle

Brofferio, A, Sachdev, V, Hannoush, H, Marshall, JD, Naggert, JK, Sidenko, S, Noreuil, A, Sirajuddin, A, Bryant, J, Han, J, Arai, AE, Gahl, WA & Gunay-Aygun, M 2017, 'Characteristics of cardiomyopathy in Alström syndrome: Prospective single-center data on 38 patients', Molecular Genetics and Metabolism, vol. 121, no. 4, pp. 336-343. https://doi.org/10.1016/j.ymgme.2017.05.017
Brofferio, Alessandra ; Sachdev, Vandana ; Hannoush, Hwaida ; Marshall, Jan D. ; Naggert, Jürgen K. ; Sidenko, Stanislav ; Noreuil, Anna ; Sirajuddin, Arlene ; Bryant, Joy ; Han, Joan ; Arai, Andrew E. ; Gahl, William A. ; Gunay-Aygun, Meral. / Characteristics of cardiomyopathy in Alström syndrome : Prospective single-center data on 38 patients. In: Molecular Genetics and Metabolism. 2017 ; Vol. 121, No. 4. pp. 336-343.
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title = "Characteristics of cardiomyopathy in Alstr{\"o}m syndrome: Prospective single-center data on 38 patients",
abstract = "Background Alstr{\"o}m 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.",
author = "Alessandra Brofferio and Vandana Sachdev and Hwaida Hannoush and Marshall, {Jan D.} and Naggert, {J{\"u}rgen K.} and Stanislav Sidenko and Anna Noreuil and Arlene Sirajuddin and Joy Bryant and Joan Han and Arai, {Andrew E.} and Gahl, {William A.} and Meral Gunay-Aygun",
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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

AU - Arai, Andrew E.

AU - Gahl, William A.

AU - Gunay-Aygun, Meral

PY - 2017/8/1

Y1 - 2017/8/1

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.

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