Children's interstitial lung disease (chILD) and specific genetic alterations (modified after [19–26])
Affected gene | Disease entity | Inheritance mode | Symptoms | Histology |
ABCA3 | Surfactant protein abnormality | Autosomal recessive | Respiratory symptoms from birth or gradually developing in later childhood | PAP, DIP, NSIP, CPI |
COPA | COPA syndrome | Autosomal dominant | Immunodysregulation affecting lung, joints, kidney, etc. | Pneumonitis, capillaritis, alveolar haemorrhage |
CSF2RA | PAP | X-associated | Dyspnoea and cough in early childhood | PAP |
CSF2RB | PAP | X-associated | Dyspnoea and cough in early childhood | PAP |
FLNA | Filamin A syndrome | X recessive | Dyspnoea in early childhood, periventricular heterotopia | Alveolar simplification |
FOXF1 | ACD/MPV | Autosomal dominant | Severe respiratory distress and pulmonary hypertension from birth | ACD/MPV |
GATA2 | PAP | Autosomal dominant | Opportunistic infections | PAP |
MARS | Interstitial lung and liver disease | Autosomal recessive | Dyspnoea and cough in early childhood, lactate acidosis, liver cirrhosis, growth retardation | PAP |
NKX2-1 | Brain–lung–thyroid syndrome | Autosomal dominant | Dyspnoea from birth, recurrent infections | DIP, CPI, PAP, alveolar simplification |
NSMCE3 | Chromosomal breakage syndrome | Autosomal recessive | Growth retardation, immune deficiency, opportunistic infections | Infections (e.g. cytomegalovirus) |
OAS1 | Infantile onset PAP | Autosomal dominant | Virus-associated pneumonia, splenomegaly | PAP |
SFTPB | Surfactant protein abnormality | Autosomal recessive | Severe dyspnoea from birth, rarely developing later | PAP, CPI |
SFTPC | Surfactant protein abnormality | Autosomal dominant | Severe dyspnoea from birth, occasionally developing later | CPI, DIP, NSIP |
SLCA7 | Lysinuric protein intolerance | Autosomal recessive | Small stature, hepatosplenomegaly, infections, later dyspnoea | PAP, infections, rarely fibrosis, if present dismal prognosis |
TBX4 | Acinar dysplasia | Autosomal dominant | Severe dyspnoea from birth, pulmonary hypertension, subluxation of patella | Acinar dysplasia, NSIP, PIG |
TMEM173 | STING-associated vasculopathy | Autosomal dominant | Systemic inflammation with skin lesions, vasculopathy, dyspnoea | CPI, follicular bronchitis |
SCL34A2 | Familial pulmonary alveolar microlithiasis | Autosomal recessive | Dyspnoea and cough in childhood | Microlithiasis |
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.