Table 1.
Respiratory manifestations in Down syndrome
| Area/Region | Manifestations | Possible Mechanisms | References |
|---|---|---|---|
| Upper airways | Macroglossia | Hypermethylation of HOXB cluster Hypermethylation of HOXB cluster Hypermethylation of HOXB cluster Hypermethylation of HOXB cluster Hypermethylation of HOXB cluster Hypermethylation of HOXB cluster ↑ PCNT |
(8) |
| Adenotonsillar hypertrophy | (8) | ||
| Laryngomalacia | (8) | ||
| Narrow trachea/tracheomalacia | (2, 9, 10) | ||
| Tracheal bronchus | (9) | ||
| Obstruction | (2, 8, 11) | ||
| Ciliopathies/increased mucus production | (12, 13) | ||
| Lower airways | Recurrent infection Poor airway clearance |
Cytokine/chemokine storm ↑ IFN pathway ↑ PCNT |
(14, 15, 16, 17, 18, 19) (14, 15, 16, 17, 18, 19) (12, 13) |
| Alveolar space | Pulmonary hypoplasia Subpleural cysts |
↑ COL6A1 ↑ COL6A1 |
(20, 21, 22) (23) |
| Vascular | Pulmonary hypertension Pulmonary hemosiderosis Pulmonary capillaritis |
↑ COL18A1, APP, TIMP3, COL4A3, RCAN1, DSCR1 ↓Clotting factors (F2, F5, F7, F12) ↑ COL18A1, APP, TIMP3, COL4A3, RCAN1, DSCR1 ↓Clotting factors (F2, F5, F7, F12) ↑ COL18A1, APP, TIMP3, COL4A3, RCAN1, DSCR1 ↓Clotting factors (F2, F5, F7, F12) |
(4, 24, 25) (21) (26, 27) (21) (28) (21) |
|
Lymphatics |
Lymphangiectasia |
↑ SHH, VEGF-A, PDG-B ↓FOXC2 ↑IFN pathways |
(12, 29) (21, 29) (21, 29) |
Disease manifestations are listed by region of the lung affected.