Abstract
The filamin A gene (FLNA) on Xq28 encodes the filamin A protein. Mutation in FLNA causes a wide spectrum of disease including skeletal dysplasia, neuronal migration abnormality, cardiovascular malformation, intellectual disability and intestinal obstruction. Recently, childhood-onset interstitial lung disease associated with a range of FLNA mutations has been recognised and reported. We document our personal experience of this emerging disorder and compile a comprehensive overview of clinical features and molecular changes in all identifiable published cases. Reviewing the emerging dataset, we underline this unanticipated phenotypic consequence of pathogenic FLNA mutation-associated pulmonary disease.
Conclusion: From the emerging data, we suggest that while reviewing complex cases with a sustained oxygen requirement against a clincial background of cardiac concerns or intestinal obstruction to have a high index of suspicion for FLNA related pathology and to instigate early MRI brain scan and FLNA mutation analysis.
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What is Known:
• FLNA gene on Xq28 encodes the filamin A protein and mutation therein is associated with variable phenotypes depending on its nature of mutation.
• Loss-of-function mutation of filamin A is associated with X-linked inherited form of periventricular nodular heterotopia with or without epilepsy with most individuals affected being female. There is a recently recognised associated respiratory phenotype.
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What is New:
• The respiratory phenotype in the form of childhood interstitial lung disease is a recently recognised clinical consequence of loss-of-function FLNA mutation.
• Rare male patients with loss-of-function FLNA mutation-associated lung disease with residual protein function can survive into infancy with a severe form of the phenotype.
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