Lung disease due to FLNA mutation improved after shunt closure for congenital heart disease
Satomi Mori MD1), Koji Tanoue MD1), Hiroyuki Shimizu MD2), Hiroyuki Nagafuchi MD2), Ki-Sung Kim MD, PhD3), Hiroaki Murakami MD, PhD4), Kenji Kurosawa MD, PhD4), Kiyoshi Matsui MD1).
  1. Department of general medicine, Kanagawa Children’s Medical Center, Yokohama, Japan
  2. Department of critical care medicine, Kanagawa Children’s Medical Center, Yokohama, Japan
  3. Department of cardiology, Kanagawa Children’s Medical Center, Yokohama, Japan
  4. Division of medical genetics, Kanagawa Children’s Medical Center, Yokohama, Japan
Corresponding author: Satomi Mori. Department of general medicine, Kanagawa Children’s Medical Center, Yokohama, Japan
Funding Source: This work was supported by tthe Initiative on Rare and Undiagnosed Diseases (19ek0109301) and MGeND (Medical Genomics Japan Variant Database (19kk0205014) from the Japan Agency for Medical Research and Development and JSPS KAKENHI 20k08270 (K. Kurosawa).
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KEYWORDS:FLNA, filamin A, interstitial lung disease, pulmonary hypertension
Running head: Shunt closure improves ILD due to FLNA mutation
Abstract
The FLNA gene encodes filamin A, an actin filament cross-linking protein that is ubiquitously expressed within the body. FLNA mutation causes periventricular nodular heterotopia (PVNH) and congenital heart disease. Interstitial lung disease (ILD) related to FLNA mutation has also been reported from 2011 and can be lethal. However, there are no reports of how to combine the treatment of heart disease with the conflicting treatment of lung disease. We herein report cases of two girls with FLNA mutation and both ILD and left-to-right shunts due to congenital heart disease. They presented with respiratory symptoms in early infancy and required management with long-term intubation and ventilation. However, their respiratory status improved subsequent to the closure of their left-to-right shunts even though they were small shunts with improvement in pulmonary hypertension. This suggests that early intervention with closure of cardiac shunts can prevent further deterioration of lung damage.
To the editor,
The FLNA gene encodes filamin A and is located at chromosome Xq28. Filamin A is an actin filament cross-linking protein and plays multiple roles in cell migration, blood vessel wall maintenance, signal transduction, and has been involved in tissue repair[1].FLNA mutation is a well-known causative gene of periventricular nodular heterotopia (PVNH). Additionally, heterozygous loss-of-function mutations exhibit various human phenotypes, such as cardiovascular disease, joint hyperextension, and thrombocytopenia. Interstitial lung disease (ILD) related to FLNA mutation was first reported in 2011[2]. We present two cases of girls with FLNA mutation and both ILD and congenital heart disease (CHD). Both showed improved respiratory status following shunt closures.