# Frequency and characteristics of emphysema in adults with FLNA variants: a single-center study

## TL;DR

This study finds that adults with FLNA gene variants often develop emphysema, a lung condition typically linked to smoking or other risk factors.

## Contribution

The study is one of the first to investigate emphysema frequency and characteristics in adults with FLNA pathogenic variants.

## Key findings

- 70% of the studied adults with FLNA variants had emphysema, mostly centrilobular and in upper lobes.
- 57.1% of emphysema cases were unexplained, lacking typical risk factors like smoking.
- Pulmonary tests showed airflow limitation and reduced lung function in emphysema patients.

## Abstract

FLNA pathogenic variants lead to various congenital malformations. Pulmonary manifestations were reported in early age. In adults, few cases of emphysema were published. We aimed to assess the frequency and characteristics of emphysema in adults with a pathogenic or probably pathogenic variant in FLNA.

We conducted a transversal single-center study. Adults with FLNA pathogenic variant followed in Lille University Hospital were identified among the French rare disease database BaMaRa®. They attended medical examination, non-contrast chest CT-scan and pulmonary function tests (PFT). We collected medical history, tobacco smoking status, occupational and domestic exposures. When emphysema was identified, the PTPN6 gene was sequenced and alpha1antitrypsin deficiency searched. The primary objective of the study was to assess the frequency of emphysema. Secondary objectives were to evaluate emphysema type, distribution and extension, lung function in case of emphysema and the frequency of unexplained emphysema.

Among the 29 patients identified, 10 met non-inclusion criteria, 4 declined, 5 could not be reached and so 10 patients were included. The frequency of emphysema was 70%. It was most often centrilobular and located in upper lobes (n = 4) with a median volume of 8.8% (IQR: 3.0–18.0%) of the total lung volume. The frequency of unexplained emphysema was estimated to be 57.1% of emphysema cases. PFT revealed airflow limitation (n = 3), reduced DLCO (n = 5) and small airway disease on IOS (n = 5).

These preliminary results suggest that adults with FLNA pathogenic variant frequently develop emphysema, allowing for a larger study to be considered.

ClinicalTrials.gov, NCT05550844, Registered 19 September 2022 https://clinicaltrials.gov/study/NCT05550844?cond=FLNA&rank=1.