TABLE 1.
Overview of genetic pulmonary diseases presenting in childhood
| Condition | Associated genes | Inheritance pattern | Pulmonary features | Additional clinical features |
|---|---|---|---|---|
| Alveolar capillary dysplasia with misalignment of pulmonary veins | FOXF1 | AD | RDS, ACD, PH | Cardiovascular, gastrointestinal, and genitourinary malformations |
| Autosomal recessive pseudohypoaldosteronism-type 1 | SCNN1A, SCNN1B, SCNN1G | AR | BE, Rl | Salt wasting, failure to thrive, and muscle weakness |
| BHD syndrome | FLCN | AD | PX, C | Cutaneous hamartomas, renal cysts, and renal cancers |
| Brain-lung-thyroid syndrome | NKX2–1 | AD | RDS, ILD, PF, NEHI | Chorea, other neurological symptoms, hypothyroidism |
| Congenital central hypoventilation syndrome | PHOX2B | AD | CH | Hirschprung’s disease, neural crest-derived tumors, autonomic dysfunction |
| Cutis laxa | FBLN5, EFEMP2, LTBP4, ELN | AR, AD | PX, E, PH | Loose, saggy, inelastic skin, hernias, visceral diverticula, joint hypermobility |
| Cystic fibrosis | CFTR | AR | BE, Rl, PX | Pancreatic insufficiency and male infertility |
| Hereditary hemorrhagic telangiectasia | ACVRL1, ENG, GDF2, SMAD4 | AD | AVMs, PAH | Telangiectasias, hepatic and cerebral AVMs, juvenile polyposis syndrome (SMAD4) |
| FLNA-Associated periventricular heterotopia | FLNA | XL | E, ILD, PAH, PX | Intellectual disability, seizures, and cardiac valvular anomalies |
| Heritable pulmonary arterial hypertension | BMPR2, ACVRL1, BMPR1B, CAV1, CBLN2, EIF2AK4, ENG, KCNA5, KCNK3, SMAD9 | AD | PAH | |
| Hermansky-Pudlak syndrome | AP3B1, AP3D1, BLOC1S3, BLOC1S6, DTNBP1, HPS1, HPS3, HPS4, HPS5, HPS6 | AR | PF, RLD | Oculocutaneous albinism, bleeding diathesis, common in Puerto Rico |
| Immune deficiencies | Over 200 genes | AR, AD, XL | BE, ILD, PAP, Rl | Various additional features depending on underlying defect |
| Loeys-Dietz syndrome | TGFBR1, TGFBR2 | AD | PX, C, RLD | Aortic dilation, skeletal deformities, bifid uvula, velvety, translucent skin |
| Marfan syndrome | FBN1 | AD | PX, E, BE, PF | Tall stature, joint laxity, aortic dilation, arachnodactyly, and ocular findings |
| Primary ciliary dyskinesia | ARMC4, C21orf59, CCDC39, CCDC40, CCDC65, CCDC103, CCDC114, CCDC151, CCDC164, CCNO, CFAP298, DNAAF1, DNAAF2, DNAAF3, DNAAF4, DNAAF5, DNAH1, DNAH5, DNAH8, DNAH11, DNAI1, DNAI2, DNAJB13, DNAL1, DRC1, HEATR2, HYDIN, GAS8, LRRC6, MCIDAS, NME8, OFD1, PIH1D3, RPGR, RSPH1, RSPH3, RSPH4A, RSPH9, SPAG1, TTC25, TXNDC3, ZMYND10 | AR, XL | BE, RDS, Rl | Laterality defects, recurrent infections, and male infertility |
| Pulmonary alveolar proteinosis | CSF2RA, CSF2RB, MARS, SLC7A7, GATA2, 22qll.2 deletion | AR | PAP | MARS, SLC7A7, NPC2, GATA2, and 22qll.2 are syndromic conditions |
| Short telomere syndromes | TERC, TERT, DKC1, TINF2, RTEL1, ACD, CTC1, NOP10, NHP2, PARN, USB1, WRAP53 | AD, AR, XL | PF, RLD, AVMs | Nail and skin abnormalities, oral leukoplakia, short stature, premature graying, genitourinary abnormalities, brain abnormalities, bone marrow failure syndromes, and cirrhosis |
| Surfactant deficiencies | ABCA3, SFTPB, SFTPC | AD, AR | RDS, ILD, PAP, PF | Failure to thrive |
| Vascular Ehlers-Danlos syndrome | COL3A1 | AD | PX, C | Easy bruising, thin and translucent skin, and tissue fragility |
Abbreviations: ACD, alveolar capillary dysplasia; AVMs, arteriovenous malformations; BE, bronchiectasis; BHD, Birt-Hogg-Dubé; C, lung cysts; CCHS, congenital central hypoventilation syndrome; CH, central hypoventilation; E, emphysema; ILD, interstitial lung disease; LDS, Loeys-Dietz syndrome; NEHI, neuroendocrine cell hyperplasia of infancy; PAH, pulmonary arterial hypertension; PAP, pulmonary alveolar proteinosis; PF, pulmonary fibrosis; PH, pulmonary hypertension; PX, pneumothorax; RDS, respiratory distress syndrome; RI, recurrent infections; RLD, restrictive lung disease.