Table 1.

Previous reports on FLNA gene variants associated with severe lung disorders

	Sex	Mutation	Principal clinical features	CT scan	Gestational age (weeks)	Age at presentation	Surgery	Documented PNVH	Outcome
Gerard-Blanluet et al., 2006 [19]	Male twins*	Missense mutation c.7922C > T (p.Pro2641Leu)	Severe bronchopulmonary dysplasia (BPD)	Not provided	26	26 weeks	None	Yes	Death of 1 infant at 8 mo; Follow-up until age 6 years (intercurrent respiratory infection)
*same family	Female*	Missense mutation c.7922C > T (p.Pro2641Leu)	Severe BPD	Not provided	24	24 weeks	None	Yes	Follow-up until age 2.5 years
De Wit et al., 2011 [9]	Female	Missense mutation c.220G > A (p.Gly74Arg)	Lobar emphysema (right middle lobe); bronchomalacia of right bronchial tree; frequent respiratory infections.	Severe lobar emphysema of right middle lobe; displacement of mediastinal structures	term	3 months	Lobectomy (right middle lobe)	Yes	Weaned from oxygen at 1 year, 7 months
Masurel-Paulet et al. 2011 [2]	Male	Mosaic nonsense mutation c.994delG (p.Lys331*)	Progression to severe lung disease	Congenital lobar emphysema;	term	3 months	Subtotal left upper lobectomy	Yes	Age 6 years. Supplemental oxygen during sleep
Clapham et al., 2012 [21]	Female	3′ FLNA deletion sparing first exon	Pulmonary emphysema involving multiple lobes	Not provided	39	2 months	None	Yes	Death at 7 months
	Female	3′ FLNA deletion and 5’FLNA duplication	Apical bullae of lung	Not provided	Not provided	ND	ND	Yes	Not provided
	Female	Deletion entire FLNA gene	Lobar emphysema	Not provided	Not provided	ND	ND	Yes	Not provided
Reinstein et al., 2013 [22]	Female (case F3)	Truncating mutation c.2193C > A (p.Tyr731*)	Pulmonary hypertension, focal hyperinflation with minimal patchy atelectasis	Not provided	Not provided	6 years	ND	Yes	Not provided
Lord et al., 2014 [17]	Female	Truncating mutation c.5683G3 > T (p.Gly1895*)	Progression to severe lung disease	Cystic pulmonary lesions;	36	24 days	none	Yes	Weaned from oxygen at 22 months
Lange et al., 2015 [20]	Male (case 29)	Mosaic non sense mutation c.7055-7070delCTTTTGCAGTCAGCCT (p.Ser2352*)	Severe progressive obstructive lung disease	Not provided	ND	38 years	Consideration of lung transplantation	Yes	Not provided
Eltahir et al., 2016 [18]	Female	Duplication c.3153dupC (p.Val1052Argfs*17)	Progressive lung disease	Lower lobe airspace disease, hyperinflation (right middle and left upper lobes)	36	2 months	PDA ligation	Not performed	Death at 15 months
Shelmerdine et al., 2017 [13]	Female	Deletion c.88delG (p.Ala30Profs*28)	Progressive lung disease	Left upper lobe and lower inflation; coarse septal thickening	36 + 5	3 months	PDA ligation	Not performed	Died at 9 months
	Female	Duplication c.6496dupA (p.lle2166Asnfs*3)	Multiple episodes of intercurrent pulmonary infections	Right upper and middle lobe over-inflation; coarse septal thickening; lower lobe atelectasis	term	7 months	Righ upper lobectomy, PDA ligation	Yes	Age 4 years
	Female	Missense mutation c.1528G > A (p.Ala510Thr)	Meconium aspiration	Right upper and left upper lobe over-inflation; coarse septal thickening; Lower lobe atelectasis	40 + 4	At birth	None	Not performed	Age 3 years. Therapy with bronchodilatator
	Female	Deletion c.2190_2193delTTAC (p.Tyr731Alafs*10)	Viral infections	Right upper and middle, left upper lobe over-inflation; Coarse septal thickening; Lower lobe atelectasis	38	3 months	None	Not performed	Age 6 years. Supplementary oxygen support
Burrage et al., 2017 [14]	Female	Duplication c.4596dupG (p.Ser1533Glufs*12)	Progressive lung disease	In all patients, severe pulmonary hyperinflation and hyperlucency with peripheral pulmonary vascular attenuation with parahilar and dependent lower lobe atelectasis and central pulmonary artery enlargement. In all patient, pulmonary arterial hypertension was also diagnosed.	39	2–4 months	PDA ligation	Yes	Lung transplantation in all. Five survivors at 19 months, 3 years, 4 years, 5.1 years, and 11.3 years respectively, post- follow-up. One died at 3 years
	Female	Missense mutationc.5290G > A (p.Ala1764Thr)	Progressive lung disease		40	neonatal	PDA ligation	Yes
	Female	Duplication c.4446_4447dupAT (p.Leu1483Tyrfs*19)	Progressive lung disease		38	neonatal	PDA ligation	Yes
	Female	Duplication c.4617_4618delGC (p.Leu1540Alafs*4)	Progressive lung disease		34	neonatal	PDA ligation	Yes
	Female	Duplication c.6585dupT (p.Pro2196Serfs*3)	Progressive lung disease		39	neonatal	PDA ligation	Yes
	Female	Missense mutation c.2807A > G (p.Lys936Arg)	Progressive lung disease		38	neonatal	PDA ligation	Yes
Kinane et al. 2017 [15]	Female	Deletion c.6577delC (p.Arg2193Alafs*14)	Diffuse pulmonary abnormalities	Ground glass opacities, area of hyperacration, pulmonary hypertension	39	30 day	PDA ligation	Yes
Sasaki et al. 2018 [16]	Female	Deletion c.1709_1712del (p.Val570Alafs*105)	Progressive lung disease	Diffuse bilateral groung-glass opacification throughout the lung, interstitial thickening, cystic changes	37	1 month	None	Yes	Died at 4 months
	Male	Splice site deletion c.6670-1delG	Several episodes of profound desaturation	Bilateral dependent and subsegmental atelectasis, scattered opacity, interstitial thickening	32	day of live 1	None	Yes	11 months, home oxigen
Our case	Male	Mosaic frameshift mutation c.7391_7403del; (p.Val2464Alafs*5)	Progressive lung disease	Lobar emphysema of the left upper lobe and a subsegmental atelectasis and areas of air trapping into the lower lobe	37	32 days	Left lobectomy Tracheostomy	Yes	15 months Mechanical ventilation

FLNA Filamin A; PNVH periventricular nodular heterotopia; CT computed tomography; PDA patent ductus arteriosus; ND Not provided