Mutation identification and prediction for severe cardiomyopathy in Alström syndrome, and review of the literature for cardiomyopathy
Abstract Objective Alström syndrome (ALMS) is a rare autosomal recessive genetic disorder that is caused by homozygous or compound heterozygous mutation in the ALMS1 gene. Dilated cardiomyopathy (DCM) is one of the well-recognized features of the syndrome ranging from sudden-onset infantile DCM to a...
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-022-02483-7 |
| _version_ | 1828148113168138240 |
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| author | Savas Dedeoglu Elif Dede Funda Oztunc Asuman Gedikbasi Gozde Yesil Reyhan Dedeoglu |
| author_facet | Savas Dedeoglu Elif Dede Funda Oztunc Asuman Gedikbasi Gozde Yesil Reyhan Dedeoglu |
| author_sort | Savas Dedeoglu |
| collection | DOAJ |
| description | Abstract Objective Alström syndrome (ALMS) is a rare autosomal recessive genetic disorder that is caused by homozygous or compound heterozygous mutation in the ALMS1 gene. Dilated cardiomyopathy (DCM) is one of the well-recognized features of the syndrome ranging from sudden-onset infantile DCM to adult-onset cardiomyopathy, sometimes of the restrictive hypertrophic form with a poor prognosis. We aimed to evaluate severe cardiomyopathy in Alström syndrome in infancy and display susceptible specific mutations of the disease, which may be linked to severe DCM. Secondarily we reviewed published mutations in ALMS1 with cardiomyopathies in the literature. Method We represent new mutagenic alleles related to severe cardiomyopathy and cardiac outcome in this patient cohort. We evaluated echocardiographic studies of nine Turkish patients diagnosed with Alström syndrome (between 2014 and 2020, at age two weeks to twenty years). Thus, we examined the cardiac manifestations of a single-centre prospective series of nine children with specific ALMS mutations and multisystem involvement. All patients underwent genetic and biochemical testing, electrocardiograms, and echocardiographic imaging to evaluate systolic strain with speckle tracking. Results Four of the patients died from cardiomyopathy. Three patients (including three of the four fatalities) with the same mutation (c.7911dupC [p.Asn2638Glnfs*24]) had cardiomyopathy with intra-familial variability in the severity of cardiomyopathy. Global longitudinal strain, a measure of systolic contractile function, was abnormal in all patients that can be measured. Conclusion Cardiac function in ALMS patients with infantile cardiomyopathy appears to have different clinical spectrums depending on the mutagenic allele. The c.7911dupC (p. Asn2638Glnfs*24) mutation can be related to severe cardiomyopathy. Parents can be informed and consulted about the progression of severe cardiomyopathy in a child carrying this mutagenic allele. |
| first_indexed | 2024-04-11T21:10:18Z |
| format | Article |
| id | doaj.art-c5028f6768bb450da73bbe2f99f54eb2 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-04-11T21:10:18Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-c5028f6768bb450da73bbe2f99f54eb22022-12-22T04:03:03ZengBMCOrphanet Journal of Rare Diseases1750-11722022-09-0117111010.1186/s13023-022-02483-7Mutation identification and prediction for severe cardiomyopathy in Alström syndrome, and review of the literature for cardiomyopathySavas Dedeoglu0Elif Dede1Funda Oztunc2Asuman Gedikbasi3Gozde Yesil4Reyhan Dedeoglu5Department of Pediatrics, Uskudar UniversityDepartment of Pediatric Cardiology, Cerrahpasa Medical School, Istanbul University-CerrahpaşaDepartment of Pediatric Cardiology, Cerrahpasa Medical School, Istanbul University-CerrahpaşaDivision of Medical Genetics, Department of Pediatric Basic Sciences, Institute of Child Health, Istanbul UniversityDepartment of Medical Genetics, Faculty of Medicine, Istanbul UniversityDepartment of Pediatric Cardiology, Cerrahpasa Medical School, Istanbul University-CerrahpaşaAbstract Objective Alström syndrome (ALMS) is a rare autosomal recessive genetic disorder that is caused by homozygous or compound heterozygous mutation in the ALMS1 gene. Dilated cardiomyopathy (DCM) is one of the well-recognized features of the syndrome ranging from sudden-onset infantile DCM to adult-onset cardiomyopathy, sometimes of the restrictive hypertrophic form with a poor prognosis. We aimed to evaluate severe cardiomyopathy in Alström syndrome in infancy and display susceptible specific mutations of the disease, which may be linked to severe DCM. Secondarily we reviewed published mutations in ALMS1 with cardiomyopathies in the literature. Method We represent new mutagenic alleles related to severe cardiomyopathy and cardiac outcome in this patient cohort. We evaluated echocardiographic studies of nine Turkish patients diagnosed with Alström syndrome (between 2014 and 2020, at age two weeks to twenty years). Thus, we examined the cardiac manifestations of a single-centre prospective series of nine children with specific ALMS mutations and multisystem involvement. All patients underwent genetic and biochemical testing, electrocardiograms, and echocardiographic imaging to evaluate systolic strain with speckle tracking. Results Four of the patients died from cardiomyopathy. Three patients (including three of the four fatalities) with the same mutation (c.7911dupC [p.Asn2638Glnfs*24]) had cardiomyopathy with intra-familial variability in the severity of cardiomyopathy. Global longitudinal strain, a measure of systolic contractile function, was abnormal in all patients that can be measured. Conclusion Cardiac function in ALMS patients with infantile cardiomyopathy appears to have different clinical spectrums depending on the mutagenic allele. The c.7911dupC (p. Asn2638Glnfs*24) mutation can be related to severe cardiomyopathy. Parents can be informed and consulted about the progression of severe cardiomyopathy in a child carrying this mutagenic allele.https://doi.org/10.1186/s13023-022-02483-7Alström syndromeSevere cardiomyopathyGenetic mutation |
| spellingShingle | Savas Dedeoglu Elif Dede Funda Oztunc Asuman Gedikbasi Gozde Yesil Reyhan Dedeoglu Mutation identification and prediction for severe cardiomyopathy in Alström syndrome, and review of the literature for cardiomyopathy Orphanet Journal of Rare Diseases Alström syndrome Severe cardiomyopathy Genetic mutation |
| title | Mutation identification and prediction for severe cardiomyopathy in Alström syndrome, and review of the literature for cardiomyopathy |
| title_full | Mutation identification and prediction for severe cardiomyopathy in Alström syndrome, and review of the literature for cardiomyopathy |
| title_fullStr | Mutation identification and prediction for severe cardiomyopathy in Alström syndrome, and review of the literature for cardiomyopathy |
| title_full_unstemmed | Mutation identification and prediction for severe cardiomyopathy in Alström syndrome, and review of the literature for cardiomyopathy |
| title_short | Mutation identification and prediction for severe cardiomyopathy in Alström syndrome, and review of the literature for cardiomyopathy |
| title_sort | mutation identification and prediction for severe cardiomyopathy in alstrom syndrome and review of the literature for cardiomyopathy |
| topic | Alström syndrome Severe cardiomyopathy Genetic mutation |
| url | https://doi.org/10.1186/s13023-022-02483-7 |
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