Cystic lung diseases constitute a heterogeneous group of difficult-to-diagnose diseases radiologically characterized by the presence of air-filled spaces surrounded by thin walls in lung parenchyma, which cause a loss of functional capacity, respiratory failure, and often pneumothorax. Some of these entities have a genetic cause, including, among others, lymphangioleiomyomatosis (LAM) associated with multiple sclerosis, Birt-Hogg-Dubé syndrome, type 1 neurofibromatosis, Ehlers-Danlos syndrome type IV, and cutis laxa.
This panel includes the study of alpha-1 antitrypsin deficiency because, although radiological involvement manifests as emphysema rather than as cysts, differential diagnosis with some of the described entities could be considered under some circumstances.
- Alpha-1 antitrypsin deficiency (A1AD) specific panel [1 gene] view panel >
It is a cystic disease that almost exclusively affects women. Its genetic form follows an autosomal dominant inheritance pattern associated with the tuberous sclerosis complex (TSC-LAM). Mutations in the TSC1 and TSC2 genes cause a loss of cell growth regulatory function of the m-TOR pathway, involved in tumor formation. Smooth muscle cells disseminated by the lymph and blood infiltrate lung tissue. This disease appears in approximately 80% of women over age 40 affected with tuberous sclerosis. Disease progression leads to respiratory failure and is often associated with extrapulmonary manifestations, with formation of benign tumors located in the brain, skin, kidney, and heart and, less frequently, with the formation of malign tumors.
Cutis laxa (CL):
Its hereditary form is caused by mutations in the ELN, FBLN5, EFEM, and LTBP54 genes, related to extracellular matrix protein synthesis in tissues. It has an estimated prevalence of 1:1,000,000 live newborns. It can manifest with autosomal dominant (ADCL) and autosomal recessive (ARCL) patterns of inheritance, with the latter leading to the most severe forms. In addition to pulmonary involvement in the form of cysts and emphysema, it is associated with skin lesions, with abundant, wrinkly, flaccid skin; developmental alterations; and malformations at the vascular, digestive, genitourinary, and skeletal levels, which can occasionally be severe
Neurofibromatosis type 1 (NF1), Birt-Hogg-Dubé syndrome (FLCN), and Ehlers-Danlos syndrome type IV (COL3A1):
All these autosomal dominant disorders are also difficult to diagnose and can be associated with defects in lung tissue characterized by the formation of cysts, bullae, or emphysema and clinically manifesting with pneumothorax, dyspnea, and respiratory failure.
- Emilio Ansótegui Barrera, Nuria Mancheño Franch, Francisco Vera-Sempere y José Padilla Alarcón. Linfangioleiomiomatosis. Arch Bronconeumol. 2011;47(2):85–93
- Miravitlles M, Dirksen A, Ferrarotti I, Koblizek V, Lange P, Mahadeva R,McElvaney NG, Parr D, Piitulainen E, Roche N, Stolk J, Thabut G, Turner A, Vogelmeier C, Stockley RA. European Respiratory Society statement: diagnosis and treatment of pulmonary disease in α(1)-antitrypsin deficiency. Eur Respir J. 2017 Nov 30;50(5).
- A.A. Dal Sasso, L.C. Belém, G. Zanetti, C.A. Souza, D.L. Escuissato, K.L. Irion, et al. Birt-Hogg-Dubé syndrome. State-of-the-art review with emphasis on pulmonary involvement. Respir Med, 109 (2015), pp. 289-29
- F.M. von Ranke, G. Zanetti, J.L. Silva, C.A. Neto, M.C. Godoy, C.A. Souza, et al. Tuberous sclerosis complex: State-of-the-art review with a focus on pulmonary involvement. Lung (2015)
- Gupta N,, Vassallo R, Wikenheiser-Brokamp KA,, McCormack FX. .Diffuse Cystic Lung Disease. Part I.Am J Respir Crit Care Med. 2015 Jun 15;191(12):1354-66