Table 1

Clinical features, genetic findings, imaging and pathology investigations, and outcome data on patients with early-onset (<12 months) FLNA-related lung disease

CaseReportSexAge at presen­tationFLNA variantInheritanceChest radiographic findingsChest CT findingsHistologyPNHOutcome
1Masurel-Paulet et al. [3]M3 monthsMosaic nonsense c.994delG p.(Lys331*)De novoAtelectasis, hyperlucent areas in midzones bilaterallySubsegmental collapse, tracheobronchomalacia, eventration of left hemidiaphragmCongenital lobar emphysema, multiple cysts, global absence of bronchial cartilage, pulmonary hypertensionYSubtotal lobectomy
NG feeds and nocturnal oxygen at 6 years
2De Wit et al.[7]F3 monthsMissense c.220G>A p.(Gly74Arg)MaternalUnknownSevere lobar emphysema with mediastinal shiftEmphysema
No inflammation
YLobectomy
Weaned off oxygen at 19 months
3Clapham etal. [8] case 1 (family 3)F2 months39-kb deletion including FLNAMaternalPulmonary emphysemaNot providedPulmonary panacinar emphysemaYDied at 7 months due to respiratory failure
4Reinstein etal. [9] case F3FNeonatalNonsense c.2193C>A p.Tyr731*De novoPulmonary hypertension, focal hyperinflation with patchy atelectasisNot providedNot providedYOn sildenafil at 6 years
Oxygen till 18 months
5Lord et al. [10]F24 days (33 weeks corrected)Nonsense c.5683G>T p.(Gly1895*)MaternalCoarse reticular pattern, hyperinflation, atelectasisGround-glass appearances, hyperinflation, cystic lesions, atelectasis, thickened interlobular septaAlveolar simplification, pulmonary hypertensionYWeaned off oxygen at 22 months
6Bickel et al. [11]FBirthSplicing c.988-1G>CUnknownNot providedGround-glass appearances, atelectasis, hyperinflation, bronchiectasisNot providedYPneumothorax at 19 months
Asthma and seizures by 9 years
7Eltahir et al. [12]F2 monthsFrameshift c.3153dupC p.(Val1052Argfs)UnknownMultiple subsegmental atelectasis and areas of air trappingBilateral lower lobe atelectasis, bilateral upper lobe hyperinflationSimplified alveoli, abnormal architectureNo MRIDied from sepsis at 15 months
8Shelmerdine et al. [13] case 1F3 monthsFrameshift c.88delG p.(Ala30fs)UnknownLeft lung hyperinflation, mediastinal shift, right lung consolidationCoarse septal thickening, left upper and lower lobe hyperinflationPoor alveolar development, thickened pulmonary arteriesNo MRIDied from respiratory failure at 9 months
9Shelmerdine et al. [13] case 2F7 monthsFrameshift c.6496dupA p.(Ile2166fs)UnknownProgressive right lung hyperinflation with mediastinal shiftRight upper and middle lobe hyperinflation, coarse septal thickening, lower lobe atelectasis, patchy ground-glass changesRight upper lobe resection, emphysematous changes, no inflammationYRight upper lobectomy at 18 months
Weaning off oxygen and pulmonary vasodilators at 4 years
10Shelmerdine et al. [13] case 3FBirthMissense c.1528G>A p.(Ala510Thr)MaternalBilateral upper lobe hyperinflation with lower lobe atelectasisWidespread emphysematous changes with hyperinflation, bronchomalacia and bronchial stenosisNot performedNo MRITracheostomy from 6 months to 2 years
Using bronchodilators for wheeze at 3 years
11Shelmerdine et al. [13] case 4F3 monthsFrameshift c.2190_2193del p.(Tyr731fs)UnknownRight upper lobe hyperinflation, right lower lobe atelectasisPulmonary artery dilatation, widespread nodular changes, bronchial wall thickeningNot performedNo MRIOn pulmonary vasodilators and home oxygen at 6 years
12Burrage et al. [6] case 1F2 monthsFrameshift c.4596dupG p.(Ser1533Glufs)De novoProgressive pulmonary hyperinflation and scattered atelectasisSevere pulmonary hyperinflation and hyperlucency, lower lobe atelectasisPulmonary artery muscularisation, deficient airway cartilageYLung transplantation at 15 months
13Burrage et al. [6] case 2FNeonatalMissense c.5290G>A p.(Ala1764Thr)De novoProgressive pulmonary hyperinflation and scattered atelectasisSevere pulmonary hyperinflation and hyperlucency, lower lobe atelectasisPulmonary artery muscularisationYLung transplantation at 5 months
14Burrage et al. [6] case 3FNeonatalFrameshift c.4446_4447dupAT p.(Leu1483Tyrfs)De novoProgressive pulmonary hyperinflation and scattered atelectasis.Severe pulmonary hyperinflation and hyperlucency, lower lobe atelectasisPulmonary artery muscularisation, deficient airway cartilageYLung transplantation at 15 months
15Burrage et al. [6] case 4FNeonatalFrameshift c.4617_4618delGC p.(Leu1540Alafs)UnknownProgressive pulmonary hyperinflation and scattered atelectasisSevere pulmonary hyperinflation and hyperlucency, lower lobe atelectasisPulmonary artery muscularisation, deficient airway cartilageYLung transplantation at 8 months
16Burrage et al. [6] case 5FNeonatalFrameshift c.6585dupT p.(Pro2196Serfs)De novoProgressive pulmonary hyperinflation and scattered atelectasisSevere pulmonary hyperinflation and hyperlucency, lower lobe atelectasisPulmonary artery muscularisation, deficient airway cartilageYLung transplantation at 11 months
17Burrage et al. [6] case 6FNeonatalMissense c.2807A>G (p.Lys936Arg)UnknownProgressive pulmonary hyperinflation and scattered atelectasisSevere pulmonary hyperinflation and hyperlucency, lower lobe atelectasisPulmonary artery muscularisation.YLung transplantation at 13 months
18Kinane et al. 2017 [14]F30 daysFrameshift c.6577delC p.(Arg2193Alafs)MaternalCardiomegaly, patchy changes bilaterallyGround-glass appearances, hyperinflation, diffuse multifocal pulmonary parenchymal anomalies, pulmonary hypertensionAbnormal vasculature, suspicion of pulmonary-capillary haemangio­matosisYDied at 5 months due to respiratory failure
19Sasaki et al. [15] case 1F4 weeksFrameshift c.1709_1712del p.(Val570Alafs)MaternalNormalGround-glass appearances diffusely, cystic changes, interstitial thickeningNot performedYOn home oxygen at 11 months
20Sasaki et al. [15] case 2M1 daySplicing c.6670-1delGMaternalPatchy bibasal opacification, atelectasis, hyperinflationSubsegmental atelectasis, scattered opacity, interstitial thickeningSimplified lung architecture, thickening of alveolar septa, abnormal vasculature, diffuse alveolar damageYDied at 4 months due to respiratory failure
21Demirel et al. [16]F1 monthFrameshift c.2020_2021delAG p.(Arg6741Glyfs)UnknownLeft sided lucencyDiffuse pulmonary hyperinflation, abnormal vasculature, patchy atelectasisAlveolar simplification, hyperinflationYHome oxygen, pulmonary vasodilators, regular steroids, PEG fed at 12 months
22Pelizzo et al. [17]M32 daysFrameshift c.7391_7403del p.(Val2464Alafs)De novoLeft sided hyperinflationSevere lobar emphysema and air trapping, subsegmental atelectasisAlveolar enlargement and simplificationYLobectomy left upper lobe and partial left lower lobe
Mechanically ventilated on parenteral nutrition at 14 months
23Yoshii et al. [18]F3 months59-kb deletion including FLNAUnknownBilateral hyperinflation, coarse linear opacitiesRight sided pulmonary emphysema, areas of atelectasisUnknownYTracheostomy at 9 months
Pulmonary vasodilators
Home ventilated at 7 years
24This caseFBirthNonsense c.676C>T p.(Arg226*)De novoBilateral hyperinflation with increased interstitial markingsNormal lung parenchyma other than general anaesthesia related dependent changesNot performedYWeaned off oxygen at 14 months

NG: nasogastric; PEG: percutaneous endoscopic gastrostomy.