Two patients with the heterozygous R189H mutation in ACTA2 and Complex congenital heart defects expands the cardiac phenotype of multisystemic smooth muscle dysfunction syndrome.
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. © 2017 Wiley Periodicals, Inc.
Department of Pediatric Cardiology, Justus-Liebig-University of Giessen, Giessen, Germany.
Thushiha
T
Logeswaran
Department of Ophthalmology, Justus-Liebig-University of Giessen, Giessen, Germany.
Christoph
C
Friedburg
Department of Pediatric Cardiology, Justus-Liebig-University of Giessen, Giessen, Germany.
Karoline
K
Hofmann
Department of Pediatric Cardiac Surgery, Justus-Liebig-University of Giessen, Giessen, Germany.
Hakan
H
Akintuerk
Center for Genomics and Transcriptomics, Tübingen, Germany.
Saskia
S
Biskup
Department of Ophthalmology, Justus-Liebig-University of Giessen, Giessen, Germany.
Michael
M
Graef
Department of Pediatric Cardiology, Justus-Liebig-University of Giessen, Giessen, Germany.
Ali
A
Rad
Department of Human Genetics, Justus-Liebig-University of Giessen, Giessen, Germany.
Axel
A
Weber
Department of Child Neurology, Justus-Liebig-University of Giessen, Giessen, Germany.
Bernd A
BA
Neubauer
Department of Pediatric Cardiology, Justus-Liebig-University of Giessen, Giessen, Germany.
Dietmar
D
Schranz
Laboratoire Cardiogénétique, Hospices Civils de Lyon, et Université Lyon 1, Lyon, France.
Patrice
P
Bouvagnet
Department of Ophthalmology, Justus-Liebig-University of Giessen, Giessen, Germany.
Birgit
B
Lorenz
Department of Child Neurology, Justus-Liebig-University of Giessen, Giessen, Germany.
Andreas
A
Hahn
D000199:Actins / Q000235:genetics*; D000328:Adult; D001014:Aortic Aneurysm / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D004374:Ductus Arteriosus, Patent / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D015785:Eye Diseases, Hereditary / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D006330:Heart Defects, Congenital / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D015878:Mydriasis / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D010641:Phenotype; D013577:Syndrome
C541116:ACTA2 protein, human; D000199:Actins
ACTA2; R179H; aortic arch coarctation; aortopulmonary window; congenital mydriasis; interrupted aortic arch; pupil dysfunction; syndrome of generalized smooth muscle dysfunction