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.

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Keywords Aorta, Congenital heart defects, Filamin A, Genetics, Mitral valve, Nervous system, Neurology, Outflow tract, Regurgitation
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Journal Clinical Research in Cardiology
de Wit, M.C.Y, de Coo, I.F.M, Lequin, M.H, Halley, D.J.J, Roos-Hesselink, J.W, & Mancini, G.M.S. (2011). Combined cardiological and neurological abnormalities due to filamin A gene mutation. Clinical Research in Cardiology, 100(1), 45–50. doi:10.1007/s00392-010-0206-y