Figures
- Figure 1
Chest radiograph on day 1.
- Figure 2
Chest radiograph on day 14.
- Figure 3
Axial T2 section from MRI brain scan at 4 weeks.
- Figure 4
Chest radiograph at 3 months.
- Figure 5
a) Coronal and (b) axial sections from CT of the chest at 11 months.
Tables
- Table 1
Clinical features, genetic findings, imaging and pathology investigations, and outcome data on patients with early-onset (<12 months) FLNA-related lung disease
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 years2 De Wit et al.[7] F 3 months Missense c.220G>A p.(Gly74Arg) Maternal Unknown Severe lobar emphysema with mediastinal shift Emphysema
No inflammationY Lobectomy
Weaned off oxygen at 19 months3 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 months5 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 years7 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 years10 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 years11 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 months23 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 years24 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.
Vol 16 Issue 1
Table of Contents
Clues beyond the lung: an unusual diagnosis in an infant with chronic lung disease
