IllnessBronchiectases, differential diagnosis

NGS +

[Sanger]

Bronchiectasis results from deregulated inflammatory responses and recurrent infections leading to progressive lung injury. The vicious cycle hypothesis assumes impairment of mucociliary clearance by initial events leading to airway infections, followed by further impairments of mucociliary function, proliferation of bacteria and further inflammation. These sequelae include irreversible dilation of the bronchi and bronchioles due to destruction of the muscle cells and elastic connective tissue of the lung epithelium. Various causes lead to the complex interaction of host and environmental factors. Impaired mucociliary clearance may be due to monogenetic diseases such as cystic fibrosis, and bronchiectasis most commonly occurs in the setting of this condition. In bronchiectasis unrelated to cystic fibrosis, numerous underlying genetic defects have been identified, such as congenital malformations (e.g. familial congenital bronchiectasis, tracheobronchomegaly), primary ciliary dyskinesia in addition to disorders of humoral immunity (hyperimmunoglobulin E syndrome, primary hypogammaglobulinemia, X-linked agammaglobulinemia). In addition, α1-antitrypsin deficiency is characterized by the development of chronic obstructive pulmonary disease partly including bronchiectasis development. Finally, also inherited connective tissue disorders (Marfan and Ehlers-Danlos syndromes) may contribute to bronchiectasis formation. Among these diverse monogenic disorders, all classical inheritance patterns are observed. Nevertheless, the cause of bronchiectasis remains unexplained in up to 40% of cases. It can be assumed that multiple genetic and environmental influences contribute to disease development in these idiopathic cases. Consequently, a negative molecular genetic result may not exclude the clinical diagnosis.

Reference: https://doi.org/10.1111/resp.13509

• Agammaglobulinemia, XL 1 (BTK)
• Allelic: Congenital bilateral absence of vas deferens (CFTR)
• Allelic: Cystic fibrosis (CFTR)
• Allelic: Hemorrhagic diathesis due to antithrombin Pittsburgh (SERPINA1)
• Allelic: Liddle syndrome 1 (SCNN1B)
• Allelic: Liddle syndrome 2 (SCNN1G)
• Allelic: Liddle syndrome 3 (SCNN1A)
• Allelic: Pseudohypoaldosteronism, type I (SCNN1A)
• Allelic: Pseudohypoaldosteronism, type I (SCNN1B)
• Allelic: Pseudohypoaldosteronism, type I (SCNN1G)
• Allelic: Sweat chloride elevation without CF (CFTR)
• Autoimmune disease, multisystem, infantile-onset, 1 (STAT3)
• Bronchiectasis with/-out elevated sweat chloride 1 (SCNN1B)
• Bronchiectasis with/-out elevated sweat chloride 2 (SCNN1A)
• Bronchiectasis with/-out elevated sweat chloride 3 (SCNN1G)
• Ciliary dyskinesia, primary, 3, with/-out situs inversus (DNAH5)
• Emphysema due to AAT deficiency (SERPINA1)
• Emphysema-cirrhosis, due to AAT deficiency (SERPINA1)
• IgE recurrent infection syndrome (STAT3)
• Immunodeficiency 14 (PIK3CD)
• Isolated growth hormone deficiency, type III, with agammaglobulinemia (BTK)