TABLE 2

Children's interstitial lung disease (chILD) and specific genetic alterations (modified after [1926])

Affected geneDisease entityInheritance modeSymptomsHistology
ABCA3Surfactant protein abnormalityAutosomal recessiveRespiratory symptoms from birth or gradually developing in later childhoodPAP, DIP, NSIP, CPI
COPACOPA syndromeAutosomal dominantImmunodysregulation affecting lung, joints, kidney, etc.Pneumonitis, capillaritis, alveolar haemorrhage
CSF2RAPAPX-associatedDyspnoea and cough in early childhoodPAP
CSF2RBPAPX-associatedDyspnoea and cough in early childhoodPAP
FLNAFilamin A syndromeX recessiveDyspnoea in early childhood, periventricular heterotopiaAlveolar simplification
FOXF1ACD/MPVAutosomal dominantSevere respiratory distress and pulmonary hypertension from birthACD/MPV
GATA2PAPAutosomal dominantOpportunistic infectionsPAP
MARSInterstitial lung and liver diseaseAutosomal recessiveDyspnoea and cough in early childhood, lactate acidosis, liver cirrhosis, growth retardationPAP
NKX2-1Brain–lung–thyroid syndromeAutosomal dominantDyspnoea from birth, recurrent infectionsDIP, CPI, PAP, alveolar simplification
NSMCE3Chromosomal breakage syndromeAutosomal recessiveGrowth retardation, immune deficiency, opportunistic infectionsInfections (e.g. cytomegalovirus)
OAS1Infantile onset PAPAutosomal dominantVirus-associated pneumonia, splenomegalyPAP
SFTPBSurfactant protein abnormalityAutosomal recessiveSevere dyspnoea from birth, rarely developing laterPAP, CPI
SFTPCSurfactant protein abnormalityAutosomal dominantSevere dyspnoea from birth, occasionally developing laterCPI, DIP, NSIP
SLCA7Lysinuric protein intoleranceAutosomal recessiveSmall stature, hepatosplenomegaly, infections, later dyspnoeaPAP, infections, rarely fibrosis, if present dismal prognosis
TBX4Acinar dysplasiaAutosomal dominantSevere dyspnoea from birth, pulmonary hypertension, subluxation of patellaAcinar dysplasia, NSIP, PIG
TMEM173STING-associated vasculopathyAutosomal dominantSystemic inflammation with skin lesions, vasculopathy, dyspnoeaCPI, follicular bronchitis
SCL34A2Familial pulmonary alveolar microlithiasisAutosomal recessiveDyspnoea and cough in childhoodMicrolithiasis

PAP: pulmonary alveolar proteinosis; DIP: desquamative interstitial pneumonia; NSIP: nonspecific interstitial pneumonia; CPI: chronic pneumonitis of infancy; ACD/MPV: alveolocapillary dysplasia with misalignment of pulmonary veins; PIG: pulmonary interstitial glycogenosis.