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).
- Department of general medicine, Kanagawa Children’s Medical Center,
Yokohama, Japan
- Department of critical care medicine, Kanagawa Children’s Medical
Center, Yokohama, Japan
- Department of cardiology, Kanagawa Children’s Medical Center,
Yokohama, Japan
- 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).
Address: Mutsukawa 2- 138-4,
Minami-ku, Yokohama, Kanagawa.
Postal code: 232-8555, Japan
Tel: +81-45-711-2351
Fax: +81-45-721-3324
E-mail:satomiforest@gmail.com
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.