Combined cardiological and neurological abnormalities due to filamin A gene mutation

Clin Res Cardiol. 2011 Jan;100(1):45-50. doi: 10.1007/s00392-010-0206-y. Epub 2010 Aug 22.


Background: Cardiac defects can be the presenting symptom in patients with mutations in the X-linked gene FLNA. Dysfunction of this gene is associated with cardiac abnormalities, especially in the left ventricular outflow tract, but can also cause a congenital malformation of the cerebral cortex. We noticed that some patients diagnosed at the neurogenetics clinic had first presented to a cardiologist, suggesting that earlier recognition may be possible if the diagnosis is suspected.

Methods and results: From the Erasmus MC cerebral malformations database 24 patients were identified with cerebral bilateral periventricular nodular heterotopia (PNH) without other cerebral cortical malformations. In six of these patients, a pathogenic mutation in FLNA was present. In five a cardiac defect was also found in the outflow tract. Four had presented to a cardiologist before the cerebral abnormalities were diagnosed.

Conclusions: The cardiological phenotype typically consists of aortic or mitral regurgitation, coarctation of the aorta or other left-sided cardiac malformations. Most patients in this category will not have a FLNA mutation, but the presence of neurological complaints, hyperlaxity of the skin or joints and/or a family history with similar cardiac or neurological problems in a possibly X-linked pattern may alert the clinician to the possibility of a FLNA mutation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / diagnosis*
  • Abnormalities, Multiple / genetics*
  • Contractile Proteins / genetics*
  • Female
  • Filamins
  • Heart Defects, Congenital / diagnosis*
  • Heart Defects, Congenital / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Microfilament Proteins / genetics*
  • Mutation*
  • Periventricular Nodular Heterotopia / diagnosis*
  • Periventricular Nodular Heterotopia / genetics*


  • Contractile Proteins
  • Filamins
  • Microfilament Proteins