Two patients with the heterozygous R189H mutation in ACTA2 and Complex congenital heart defects expands the cardiac phenotype of multisystemic smooth muscle dysfunction syndrome

Mar 23, 2017American journal of medical genetics. Part A

Two patients with a specific ACTA2 gene mutation and complex birth heart defects expand the known heart problems in multisystem smooth muscle dysfunction syndrome

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Abstract

De novo heterozygous mutations in the ACTA2 gene are associated with Multisystemic Smooth Muscle Dysfunction Syndrome (MSMDS).

  • Mutations changing R179 to histidine, leucine, or cysteine in ACTA2 are linked to MSMDS.
  • Key features of MSMDS include congenital mydriasis, a large persistent ductus arteriosus, aortic aneurysms in childhood, and cerebrovascular anomalies.
  • Two patients, a newborn and a 26-year-old, exhibited a huge ductus arteriosus and aorto-pulmonary window due to these mutations.
  • One patient had an aortic arch coarctation, while the other had a complete interruption of the aortic arch type A.
  • These findings suggest a need for functional alpha 2 smooth muscle actin in cardiovascular organ development.

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