Journal article

Two Patients with the Heterozygous R189H Mutation in ACTA2 and Complex Congenital Heart Defects Expands the Cardiac Phenotype of Multisystemic Smooth Muscle Dysfunction Syndrome


Authors listLogeswaran, Thushiha; Friedburg, Christoph; Hofmann, Karoline; Akintuerk, Hakan; Biskup, Saskia; Graef, Michael; Rad, Ali; Weber, Axel; Neubauer, Bernd A.; Schranz, Dietmar; Bouvagnet, Patrice; Lorenz, Birgit; Hahn, Andreas

Publication year2017

Pages959-965

JournalThe American Journal of Medical Genetics - Part A

Volume number173

Issue number4

ISSN1552-4825

eISSN1552-4833

DOI Linkhttps://doi.org/10.1002/ajmg.a.38102

PublisherWiley


Abstract
De novo heterozygous mutations changing R179 to histidine, leucine, or cysteine in the ACTA2 gene are associated with Multisystemic Smooth Muscle Dysfunction Syndrome (MSMDS). Characteristic hallmarks of this condition, caused only by these specific ACTA2 mutations, are congenital mydriasis (mid-dilated, non-reactive pupils), a large persistent ductus arteriosus (PDA), aortic aneurysms evolving during childhood, and cerebrovascular anomalies. We describe two patients, a 3-day-old newborn and a 26-year-old woman, with this unique mutation in association with a huge PDA and an aorto-pulmonary window. In addition, one showed a coarctation of the aortic arch and the other a complete interruption of the aortic arch type A; thereby expanding the spectrum of cardiac congenital heart defect of this syndrome. Each patient displayed a huge PDA and an extra-cardiovascular phenotype consistent with MSMDS. These observations exemplify that a functional alpha 2 smooth muscle actin is necessary for proper cardiovascular organ development, and demonstrate that a very exceptional congenital heart defect (aortopulmonary window) can be caused by a mutation in a gene encoding a contractile protein of vascular smooth muscle cells. (C) 2017 Wiley Periodicals, Inc.



Citation Styles

Harvard Citation styleLogeswaran, T., Friedburg, C., Hofmann, K., Akintuerk, H., Biskup, S., Graef, M., et al. (2017) Two Patients with the Heterozygous R189H Mutation in ACTA2 and Complex Congenital Heart Defects Expands the Cardiac Phenotype of Multisystemic Smooth Muscle Dysfunction Syndrome, The American Journal of Medical Genetics - Part A, 173(4), pp. 959-965. https://doi.org/10.1002/ajmg.a.38102

APA Citation styleLogeswaran, T., Friedburg, C., Hofmann, K., Akintuerk, H., Biskup, S., Graef, M., Rad, A., Weber, A., Neubauer, B., Schranz, D., Bouvagnet, P., Lorenz, B., & Hahn, A. (2017). Two Patients with the Heterozygous R189H Mutation in ACTA2 and Complex Congenital Heart Defects Expands the Cardiac Phenotype of Multisystemic Smooth Muscle Dysfunction Syndrome. The American Journal of Medical Genetics - Part A. 173(4), 959-965. https://doi.org/10.1002/ajmg.a.38102



Keywords


ACTA2aortic arch coarctationAORTOPULMONARY SEPTAL-DEFECTaortopulmonary windowcongenital mydriasisDISSECTIONSinterrupted aortic archpupil dysfunctionR179Hsyndrome of generalized smooth muscle dysfunctionTHORACIC AORTIC-ANEURYSMS

Last updated on 2025-21-05 at 18:30