Case | Report | Sex | Age at presentation | FLNA variant | Inheritance | Chest radiographic findings | Chest CT findings | Histology | PNH | Outcome |
1 | Masurel-Paulet et al. [3] | M | 3 months | Mosaic nonsense c.994delG p.(Lys331*) | De novo | Atelectasis, hyperlucent areas in midzones bilaterally | Subsegmental collapse, tracheobronchomalacia, eventration of left hemidiaphragm | Congenital lobar emphysema, multiple cysts, global absence of bronchial cartilage, pulmonary hypertension | Y | Subtotal lobectomy NG feeds and nocturnal oxygen at 6 years |
2 | De Wit et al.[7] | F | 3 months | Missense c.220G>A p.(Gly74Arg) | Maternal | Unknown | Severe lobar emphysema with mediastinal shift | Emphysema No inflammation | Y | Lobectomy Weaned off oxygen at 19 months |
3 | Clapham etal. [8] case 1 (family 3) | F | 2 months | 39-kb deletion including FLNA | Maternal | Pulmonary emphysema | Not provided | Pulmonary panacinar emphysema | Y | Died at 7 months due to respiratory failure |
4 | Reinstein etal. [9] case F3 | F | Neonatal | Nonsense c.2193C>A p.Tyr731* | De novo | Pulmonary hypertension, focal hyperinflation with patchy atelectasis | Not provided | Not provided | Y | On sildenafil at 6 years Oxygen till 18 months |
5 | Lord et al. [10] | F | 24 days (33 weeks corrected) | Nonsense c.5683G>T p.(Gly1895*) | Maternal | Coarse reticular pattern, hyperinflation, atelectasis | Ground-glass appearances, hyperinflation, cystic lesions, atelectasis, thickened interlobular septa | Alveolar simplification, pulmonary hypertension | Y | Weaned off oxygen at 22 months |
6 | Bickel et al. [11] | F | Birth | Splicing c.988-1G>C | Unknown | Not provided | Ground-glass appearances, atelectasis, hyperinflation, bronchiectasis | Not provided | Y | Pneumothorax at 19 months Asthma and seizures by 9 years |
7 | Eltahir et al. [12] | F | 2 months | Frameshift c.3153dupC p.(Val1052Argfs) | Unknown | Multiple subsegmental atelectasis and areas of air trapping | Bilateral lower lobe atelectasis, bilateral upper lobe hyperinflation | Simplified alveoli, abnormal architecture | No MRI | Died from sepsis at 15 months |
8 | Shelmerdine et al. [13] case 1 | F | 3 months | Frameshift c.88delG p.(Ala30fs) | Unknown | Left lung hyperinflation, mediastinal shift, right lung consolidation | Coarse septal thickening, left upper and lower lobe hyperinflation | Poor alveolar development, thickened pulmonary arteries | No MRI | Died from respiratory failure at 9 months |
9 | Shelmerdine et al. [13] case 2 | F | 7 months | Frameshift c.6496dupA p.(Ile2166fs) | Unknown | Progressive right lung hyperinflation with mediastinal shift | Right upper and middle lobe hyperinflation, coarse septal thickening, lower lobe atelectasis, patchy ground-glass changes | Right upper lobe resection, emphysematous changes, no inflammation | Y | Right upper lobectomy at 18 months Weaning off oxygen and pulmonary vasodilators at 4 years |
10 | Shelmerdine et al. [13] case 3 | F | Birth | Missense c.1528G>A p.(Ala510Thr) | Maternal | Bilateral upper lobe hyperinflation with lower lobe atelectasis | Widespread emphysematous changes with hyperinflation, bronchomalacia and bronchial stenosis | Not performed | No MRI | Tracheostomy from 6 months to 2 years Using bronchodilators for wheeze at 3 years |
11 | Shelmerdine et al. [13] case 4 | F | 3 months | Frameshift c.2190_2193del p.(Tyr731fs) | Unknown | Right upper lobe hyperinflation, right lower lobe atelectasis | Pulmonary artery dilatation, widespread nodular changes, bronchial wall thickening | Not performed | No MRI | On pulmonary vasodilators and home oxygen at 6 years |
12 | Burrage et al. [6] case 1 | F | 2 months | Frameshift c.4596dupG p.(Ser1533Glufs) | De novo | Progressive pulmonary hyperinflation and scattered atelectasis | Severe pulmonary hyperinflation and hyperlucency, lower lobe atelectasis | Pulmonary artery muscularisation, deficient airway cartilage | Y | Lung transplantation at 15 months |
13 | Burrage et al. [6] case 2 | F | Neonatal | Missense c.5290G>A p.(Ala1764Thr) | De novo | Progressive pulmonary hyperinflation and scattered atelectasis | Severe pulmonary hyperinflation and hyperlucency, lower lobe atelectasis | Pulmonary artery muscularisation | Y | Lung transplantation at 5 months |
14 | Burrage et al. [6] case 3 | F | Neonatal | Frameshift c.4446_4447dupAT p.(Leu1483Tyrfs) | De novo | Progressive pulmonary hyperinflation and scattered atelectasis. | Severe pulmonary hyperinflation and hyperlucency, lower lobe atelectasis | Pulmonary artery muscularisation, deficient airway cartilage | Y | Lung transplantation at 15 months |
15 | Burrage et al. [6] case 4 | F | Neonatal | Frameshift c.4617_4618delGC p.(Leu1540Alafs) | Unknown | Progressive pulmonary hyperinflation and scattered atelectasis | Severe pulmonary hyperinflation and hyperlucency, lower lobe atelectasis | Pulmonary artery muscularisation, deficient airway cartilage | Y | Lung transplantation at 8 months |
16 | Burrage et al. [6] case 5 | F | Neonatal | Frameshift c.6585dupT p.(Pro2196Serfs) | De novo | Progressive pulmonary hyperinflation and scattered atelectasis | Severe pulmonary hyperinflation and hyperlucency, lower lobe atelectasis | Pulmonary artery muscularisation, deficient airway cartilage | Y | Lung transplantation at 11 months |
17 | Burrage et al. [6] case 6 | F | Neonatal | Missense c.2807A>G (p.Lys936Arg) | Unknown | Progressive pulmonary hyperinflation and scattered atelectasis | Severe pulmonary hyperinflation and hyperlucency, lower lobe atelectasis | Pulmonary artery muscularisation. | Y | Lung transplantation at 13 months |
18 | Kinane et al. 2017 [14] | F | 30 days | Frameshift c.6577delC p.(Arg2193Alafs) | Maternal | Cardiomegaly, patchy changes bilaterally | Ground-glass appearances, hyperinflation, diffuse multifocal pulmonary parenchymal anomalies, pulmonary hypertension | Abnormal vasculature, suspicion of pulmonary-capillary haemangiomatosis | Y | Died at 5 months due to respiratory failure |
19 | Sasaki et al. [15] case 1 | F | 4 weeks | Frameshift c.1709_1712del p.(Val570Alafs) | Maternal | Normal | Ground-glass appearances diffusely, cystic changes, interstitial thickening | Not performed | Y | On home oxygen at 11 months |
20 | Sasaki et al. [15] case 2 | M | 1 day | Splicing c.6670-1delG | Maternal | Patchy bibasal opacification, atelectasis, hyperinflation | Subsegmental atelectasis, scattered opacity, interstitial thickening | Simplified lung architecture, thickening of alveolar septa, abnormal vasculature, diffuse alveolar damage | Y | Died at 4 months due to respiratory failure |
21 | Demirel et al. [16] | F | 1 month | Frameshift c.2020_2021delAG p.(Arg6741Glyfs) | Unknown | Left sided lucency | Diffuse pulmonary hyperinflation, abnormal vasculature, patchy atelectasis | Alveolar simplification, hyperinflation | Y | Home oxygen, pulmonary vasodilators, regular steroids, PEG fed at 12 months |
22 | Pelizzo et al. [17] | M | 32 days | Frameshift c.7391_7403del p.(Val2464Alafs) | De novo | Left sided hyperinflation | Severe lobar emphysema and air trapping, subsegmental atelectasis | Alveolar enlargement and simplification | Y | Lobectomy left upper lobe and partial left lower lobe Mechanically ventilated on parenteral nutrition at 14 months |
23 | Yoshii et al. [18] | F | 3 months | 59-kb deletion including FLNA | Unknown | Bilateral hyperinflation, coarse linear opacities | Right sided pulmonary emphysema, areas of atelectasis | Unknown | Y | Tracheostomy at 9 months Pulmonary vasodilators Home ventilated at 7 years |
24 | This case | F | Birth | Nonsense c.676C>T p.(Arg226*) | De novo | Bilateral hyperinflation with increased interstitial markings | Normal lung parenchyma other than general anaesthesia related dependent changes | Not performed | Y | Weaned off oxygen at 14 months |
NG: nasogastric; PEG: percutaneous endoscopic gastrostomy.