A review of filamin A mutations and associated interstitial lung disease

Eur J Pediatr. 2019 Feb;178(2):121-129. doi: 10.1007/s00431-018-3301-0. Epub 2018 Dec 13.


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.

Keywords: Childhood interstitial lung disease; FLNA; Lung transplant; Periventricular nodular heterotopia; Persistent pulmonary hypertension.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Child
  • Child, Preschool
  • Female
  • Filamins / genetics*
  • Humans
  • Infant
  • Lung / pathology
  • Lung Diseases, Interstitial / diagnosis
  • Lung Diseases, Interstitial / genetics*
  • Lung Diseases, Interstitial / therapy
  • Magnetic Resonance Imaging
  • Male
  • Mutation
  • Periventricular Nodular Heterotopia / genetics
  • Phenotype
  • Tomography, X-Ray Computed
  • Ultrasonography, Doppler, Transcranial


  • FLNA protein, human
  • Filamins