Combined cardiological and neurological abnormalities due to filamin A gene mutation
Marie Claire Y de Wit1, Irenaeus F M de Coo, Maarten H Lequin
1Department of Neurology, Erasmus MC, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Insights
Mutations in the FLNA gene can cause cardiac defects and cerebral malformations. Early recognition of cardiac symptoms may lead to earlier diagnosis of FLNA-associated neurodevelopmental disorders.
Area of Science:
- Genetics
- Cardiology
- Neurology
Background:
- Mutations in the X-linked Filamin A (FLNA) gene are associated with cardiac defects, particularly in the left ventricular outflow tract.
- FLNA gene dysfunction can also lead to congenital cerebral cortical malformations.
Observation:
- Researchers identified 24 patients with bilateral periventricular nodular heterotopia (PNH) from a cerebral malformations database.
- Six of these patients had pathogenic FLNA mutations, and five also presented with outflow tract cardiac defects.
Findings:
- Four patients with FLNA mutations and PNH were initially seen by a cardiologist before their neurological condition was diagnosed.
- The study highlights that FLNA mutations can manifest with cardiac issues before neurological symptoms are apparent.
Implications:
- Recognizing cardiac abnormalities, such as aortic regurgitation or coarctation of the aorta, in patients with neurological complaints may suggest an underlying FLNA mutation.
- Considering FLNA gene mutations in cases of X-linked cardiac and neurological disorders, especially with hyperlaxity, can improve diagnostic timelines.
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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