European Journal of Pediatrics

, Volume 178, Issue 2, pp 121–129 | Cite as

A review of filamin A mutations and associated interstitial lung disease

  • Erina SasakiEmail author
  • Angela T. Byrne
  • Ethna Phelan
  • Desmond W. Cox
  • William Reardon


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.

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.

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.


FLNA Childhood interstitial lung disease Periventricular nodular heterotopia Persistent pulmonary hypertension Lung transplant 



Filamin A


Periventricular nodular heterotopia


Online Mendelian Inheritance in Man




Patent ductus arteriosus


Uni-parental disomy


High-resolution computed tomography


Authors' contributions

W.R and DW.C conceived the presenting review. E.S took lead in data collection and writing the manuscript with support of DW.C and W.R. AT.B and E.P supported analysing data. All authors provided critical feedback and helped shape the analysis and manuscript.

Compliance with ethical standards

Patient details are published with consent.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Clinical Genetics DepartmentOur Lady’s Children’s HospitalDublinIreland
  2. 2.Paediatric Radiology DepartmentOur Lady’s Children’s HospitalDublinIreland
  3. 3.Paediatric Respiratory DepartmentOur Lady’s Children’s HospitalDublinIreland
  4. 4.School of MedicineUniversity College DublinDublinIreland

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