Rare Diffuse Lung Diseases of Genetic Origin

  • Paolo Spagnolo


Diffuse parenchymal lung diseases of genetic origin constitute a large and heterogeneous group of disorders that result from the transmission of mutations from a parent or ancestor. In the context of these rare entities pulmonary involvement may represent only one end of a wide spectrum of clinical manifestations. Pattern of inheritance and age of onset are highly variable: for instance, inborn errors of metabolism associated with a diffuse parenchymal lung disease are inherited in an autosomal recessive fashion, while telomerase-associated pulmonary fibrosis is inherited in an autosomal dominant one. In this latter case, younger and more severely affected individuals in successive generations can be observed (genetic anticipation). In addition, if there is reduced penetrance and variable expressivity, a patient may demonstrate only a subset of all possible clinical manifestations.

Diffuse parenchymal lung diseases of genetic origin are challenging for a number of reasons, including their low incidence and prevalence, which hamper the acquisition of expertise and frequently delays the diagnosis, and the incomplete knowledge of disease mechanisms, which, in turn, leads to the use of empirical – and often ineffective – therapeutic strategies. This implies that the primary goal of the treating physician should be the early recognition that a rare lung disease might be present (positive family history, absence of known risk factors for diffuse parenchymal lung diseases in full-term infants, and failure to improve in the expected time frame should prompt consideration of one of these disorders), and the referral to centres with specific expertise. Making the right diagnosis may not only prevent fatal complications in affected subjects but also lead to early diagnosis of the disease in other family members.


Diffuse parenchymal lung diseases Lung fibrosis Rare lung diseases Genetic predisposition Genetics Lysosomal lipid storage disease Surfactant dysfunction disorders 



Dyskeratosis congenita


Hermansky-Pudlak syndrome


High resolution computed tomography


Interstitial lung disease


Neurofibromatosis 1


Niemann-Pick C


Niemann-Pick disease


Nonspecific interstitial pneumonia


Surfactant protein


Usual interstitial pneumonia


  1. 1.
    Thomas AQ, Lane K, Phillips III J, Prince M, Markin C, Speer M, et al. Heterozygosity for a surfactant protein c gene mutation associated with usual interstitial pneumonitis and cellular nonspecific interstitial pneumonitis in one kindred. Am J Respir Crit Care Med. 2002;165:1322–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Nogee LM, Dunbar III AE, Wert SE, Askin F, Hamvas A, Whitsett JA. A mutation in the surfactant protein C gene associated with familial interstitial lung disease. N Engl J Med. 2001;344:573–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Lawson WE, Grant SW, Ambrosini V, Womble KE, Dawson EP, Lane KB, et al. Genetic mutations in surfactant protein C are a rare cause of sporadic cases of IPF. Thorax. 2004;59:977–80.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Wang Y, Kuan PJ, Xing C, Cronkhite JT, Torres F, Rosenblatt RL, et al. Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung cancer. Am J Hum Genet. 2009;84:52–9.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Armanios MY, Chen JJ, Cogan JD, Alder JK, Ingersoll RG, Markin C, et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med. 2007;356:1317–26.PubMedCrossRefGoogle Scholar
  6. 6.
    Tsakiri KD, Cronkhite JT, Kuan PJ, Xing C, Raghu G, Weissler JC, Rosenblatt RL, Shay JW, Garcia CK. Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proc Natl Acad Sci U S A. 2007;104:7552–7.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Diaz de Leon A, Cronkhite JT, Katzenstein AL, Godwin JD, Raghu G, Glazer CS, et al. Telomere lengths, pulmonary fibrosis and telomerase (TERT) mutations. PLoS One. 2010;5:e10680.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Seibold MA, Wise AL, Speer MC, Steele MP, Brown KK, Loyd JE, et al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med. 2011;364:1503–12.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Steele MP, Speer MC, Loyd JE, Brown KK, Herron A, Slifer SH, et al. Clinical and pathological features of familial interstitial pneumonia. Am J Respir Crit Care Med. 2005;172:1146–52.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Hermansky F, Pudlak P. Albinism associated with hemorrhagic diathesis and unusual pigmented reticular cells in the bone marrow: report of two cases with histochemical studies. Blood. 1959;14:162–9.PubMedGoogle Scholar
  11. 11.
    Huizing M, Gahl WA. Disorders of vesicles of lysosomal lineage: the Hermansky-Pudlak syndromes. Curr Mol Med. 2002;2:451–67.PubMedCrossRefGoogle Scholar
  12. 12.
    Wei ML. Hermansky-Pudlak syndrome: a disease of protein trafficking and organelle function. Pigment Cell Res. 2006;19:19–42.PubMedCrossRefGoogle Scholar
  13. 13.
    Wildenberg SC, Oetting WS, Almodóvar C, Krumwiede M, White JG, King RA. A gene causing Hermansky-Pudlak syndrome in a Puerto Rican population maps to chromosome 10q2. Am J Hum Genet. 1995;57:755–65.PubMedCentralPubMedGoogle Scholar
  14. 14.
    Gahl WA, Brantly M, Kaiser-Kupfer MI, Iwata F, Hazelwood S, Shotelersuk V, et al. Genetic defects and clinical characteristics of patients with a form of oculocutaneous albinism (Hermansky-Pudlak syndrome). N Engl J Med. 1998;338:1258–65.PubMedCrossRefGoogle Scholar
  15. 15.
    Witkop CJ, Krumwiede M, Sedano H, White JG. Reliability of absent platelet dense bodies as a diagnostic criterion for Hermansky-Pudlak syndrome. Am J Hematol. 1987;26:305–11.PubMedCrossRefGoogle Scholar
  16. 16.
    Di Pietro SM, Dell’Angelica EC. The cell biology of Hermansky-Pudlak syndrome: recent advances. Traffic. 2005;6:525–33.PubMedCrossRefGoogle Scholar
  17. 17.
    Brantly M, Anderson PD, Parker MS, Rosado Shipley W, de Christenson ML, Slutzker AD, Carroll FE, Worrell JA, White JG. The Hermansky-Pudlak syndrome. Ann Diagn Pathol. 1997;1:99–103.CrossRefGoogle Scholar
  18. 18.
    Mahavadi P, Korfei M, Henneke I, Liebisch G, Schmitz G, Gochuico BR, et al. Epithelial stress and apoptosis underlie Hermansky-Pudlak syndrome-associated interstitial pneumonia. Am J Respir Crit Care Med. 2010;182:207–19.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Avila NA, Brantly M, Premkumar A, et al. Hermansky-Pudlak syndrome: radiography and CT of the chest compared with pulmonary function tests and genetic studies. AJR Am J Roentgenol. 2002;179:887–92.PubMedCrossRefGoogle Scholar
  20. 20.
    Nakatani Y, Nakamura N, Sano J, Inayama Y, Kawano N, Yamanaka S, et al. Interstitial pneumonia in Hermansky-Pudlak syndrome: significance of florid foamy swelling/degeneration (giant lamellar body degeneration) of type-2 pneumocytes. Virchows Arch. 2000;437:304–13.PubMedCrossRefGoogle Scholar
  21. 21.
    Gahl WA, Brantly M, Troendle J, Avila NA, Padua A, Montalvo C, Cardona H, Calis KA, Gochuico B. Effect of pirfenidone on the pulmonary fibrosis of Hermansky-Pudlak syndrome. Mol Genet Metab. 2002;76:234–42.PubMedCrossRefGoogle Scholar
  22. 22.
    Calado RT, Young NS. Telomere diseases. N Engl J Med. 2009;361:2353–65.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Morla M, Busquets X, Pons J, Sauleda J, MacNee W, Agusti AG. Telomere shortening in smokers with and without COPD. Eur Respir J. 2006;27:525–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Nelson ND, Bertuch AA. Dyskeratosis congenita as a disorder of telomere maintenance. Mutat Res. 2012;730:43–51.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Dokal I. Dyskeratosis congenita in all its forms. Br J Haematol. 2000;110:768–79.PubMedCrossRefGoogle Scholar
  26. 26.
    Armanios M, Chen JL, Chang YP, Brodsky RA, Hawkins A, Griffin CA, et al. Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita. Proc Natl Acad Sci U S A. 2005;102:15960–4.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Verra F, Kouzan S, Saiag P, Bignon J, de Cremoux H. Bronchoalveolar disease in dyskeratosis congenita. Eur Respir J. 1992;5:497–9.PubMedGoogle Scholar
  28. 28.
    Alder JK, Chen JJ, Lancaster L, Danoff S, Su SC, Cogan JD, et al. Short telomeres are a risk factor for idiopathic pulmonary fibrosis. Proc Natl Acad Sci U S A. 2008;105:13051–6.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of lysosomal storage disorders. J Am Med Assoc. 1999;281:249–54.CrossRefGoogle Scholar
  30. 30.
    Campbell TN, Choy FY. Gaucher disease and the synucleinopathies: refining the relationship. Orphanet J Rare Dis. 2012;7:12.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Hruska KS, LaMarca ME, Scott CR, Sidransky E. Gaucher disease: mutation and polymorphism spectrum in the glucocerebrosidase gene (GBA). Hum Mutat. 2008;29:567–83.PubMedCrossRefGoogle Scholar
  32. 32.
    Beutler E, Gelbart T, Scott CR. Hematologically important mutations: Gaucher disease. Blood Cell Mol Dis. 2005;35:355–64.CrossRefGoogle Scholar
  33. 33.
    Harmanci O, Bayraktar Y. Gaucher disease: new developments in treatment and etiology. World J Gastroenterol. 2008;14:3968–73.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Miller A, Brown LK, Pastores GM, Desnick RJ. Pulmonary involvement in type 1 Gaucher disease: functional and exercise findings in patients with and without clinical interstitial lung disease. Clin Genet. 2003;63:368–76.PubMedCrossRefGoogle Scholar
  35. 35.
    Santamaria F, Parenti G, Guidi G, Filocamo M, Strisciuglio P, Grillo G, et al. Pulmonary manifestations of Gaucher disease: an increased risk for L444P homozygotes? Am J Respir Crit Care Med. 1998;157:985–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Mistry PK, Sirrs S, Chan A, Pritzker MR, Duffy TP, Grace ME, Meeker DP, Goldman ME. Pulmonary hypertension in type 1 Gaucher’s disease: genetic and epigenetic determinants of phenotype and response to therapy. Mol Genet Metab. 2002;77:91–8.PubMedCrossRefGoogle Scholar
  37. 37.
    de Fost M, Aerts JM, Hollak CE. Gaucher disease: from fundamental research to effective therapeutic interventions. Neth J Med. 2003;61:3–8.PubMedGoogle Scholar
  38. 38.
    Goitein O, Elstein D, Abrahamov A, Hadas-Halpern I, Melzer E, Kerem E, Zimran A. Lung involvement and enzyme replacement therapy in Gaucher’s disease. QJM. 2001;94:407–15.PubMedCrossRefGoogle Scholar
  39. 39.
    Schuchman EH. The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease. J Inherit Metab Dis. 2007;30:654–63.PubMedCrossRefGoogle Scholar
  40. 40.
    Levran O, Desnick RJ, Schuchman EH. Niemann-Pick type B disease: identification of a single codon deletion in the acid sphingomyelinase gene and genotype/phenotype correlations in type A and B patients. J Clin Invest. 1991;88:806–10.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Vanier MT. Niemann-Pick disease type C. Orphanet J Rare Dis. 2010;5:16.Google Scholar
  42. 42.
    Sleat DE, Wiseman JA, El Banna M, Price SM, Verot L, Shen MM, Tint GS, Vanier MT, Walkley SU, Lobel P. Genetic evidence for nonredundant functional cooperativity between NPC1 and NPC2 in lipid transport. Proc Natl Acad Sci U S A. 2004;101:5886–91.PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Kwon HJ, Abi-Mosleh L, Wang ML, Deisenhofer J, Goldstein JL, Brown MS, Infante RE. Structure of N-terminal domain of NPC1 reveals distinct subdomains for binding and transfer of cholesterol. Cell. 2009;137:1213–24.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Millat G, Chikh K, Naureckiene S, Sleat DE, Fensom AH, Higaki K, Elleder M, Lobel P, Vanier MT. Niemann-Pick disease type C: spectrum of HE1 mutations and genotype/phenotype correlations in the NPC2 group. Am J Hum Genet. 2001;69:1013–21.PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Mendelson DS, Wasserstein MP, Desnick RJ, Glass R, Simpson W, Skloot G, et al. Type B Niemann-Pick disease: findings at chest radiography, thin-section CT, and pulmonary function testing. Radiology. 2006;238:339–45.PubMedCrossRefGoogle Scholar
  46. 46.
    Nicholson AG, Florio R, Hansell DM, du Bois RM, Wells AU, Hughes P, et al. Pulmonary involvement by Niemann-Pick disease. A report of six cases. Histopathology. 2006;48:596–603.PubMedCrossRefGoogle Scholar
  47. 47.
    Gogus S, Gocmen A, Kocak N, Kiper N, Küçükali T, Yüce A, Büyükpamukçü N. Lipidosis with sea-blue histiocytes. Report of two siblings with lung involvement. Turk J Pediatr. 1994;36:139–44.PubMedGoogle Scholar
  48. 48.
    Clarke JT. Narrative review: Fabry disease. Ann Intern Med. 2007;146:425–33.PubMedCrossRefGoogle Scholar
  49. 49.
    Branton MH, Schiffmann R, Sabnis SG, Murray GJ, Quirk JM, Altarescu G, et al. Natural history of Fabry renal disease: influence of α-galactosidase A activity and genetic mutations on clinical course. Medicine. 2002;81:122–38.PubMedCrossRefGoogle Scholar
  50. 50.
    Shirai T, Ohtake T, Kimura M, Iwata M, Fujigaki Y, Takayanagi S, Chida K, Nakamura H, Hishida A, Irie F. Atypical Fabry’s disease presenting with cholesterol crystal embolization. Intern Med. 2000;39:646–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Rosenberg DM, Ferrans VJ, Fulmer JD, Line BR, Barranger JA, Brady RO, Crystal RG. Chronic airflow obstruction in Fabry’s disease. Am J Med. 1980;68:898–905.PubMedCrossRefGoogle Scholar
  52. 52.
    Eng CM, Guffon N, Wilcox WR, Germain DP, Lee P, Waldek S, Caplan L, Linthorst GE, Desnick RJ, International Collaborative Fabry Disease Study Group. Safety and efficacy of recombinant human alpha-galactosidase A – replacement therapy in Fabry’s disease. N Engl J Med. 2001;345:9–16.PubMedCrossRefGoogle Scholar
  53. 53.
    Simell O, Perheentupa J, Rapola J, Visakorpi JK, Eskelin LE. Lysinuric protein intolerance. Am J Med. 1975;59:229–40.PubMedCrossRefGoogle Scholar
  54. 54.
    Mykkanen J, Torrents D, Pineda M, Camps M, Yoldi ME, Horelli-Kuitunen N, et al. Functional analysis of novel mutations in y(þ)LAT-1 amino acid transporter gene causing lysinuric protein intolerance (LPI). Hum Mol Genet. 2000;9:431–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Parto K, Svedstrom E, Majurin ML, Härkönen R, Simell O. Pulmonary manifestations in lysinuric protein intolerance. Chest. 1993;104:1176–82.PubMedCrossRefGoogle Scholar
  56. 56.
    Ceruti M, Rodi G, Stella GM, Adami A, Bolongaro A, Baritussio A, Pozzi E, Luisetti M. Successful whole lung lavage in pulmonary alveolar proteinosis secondary to lysinuric protein intolerance: a case report. Orphanet J Rare Dis. 2007;2:14.PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Auwerx J, Demedts M, Bouillon R, Desmet J. Coexistence of hypocalciuric hypercalcaemia and interstitial lung disease in a family: a cross-sectional study. Eur J Clin Invest. 1985;15:6–14.PubMedCrossRefGoogle Scholar
  58. 58.
    Pearce SHS, Wooding C, Davies M, Tollefsen SE, Whyte MP, Thakker RV. Calcium-sensing receptor mutations in familial hypocalciuric hypercalcaemia with recurrent pancreatitis. Clin Endocrinol (Oxf). 1996;45:675–80.CrossRefGoogle Scholar
  59. 59.
    Volpe A, Guerriero A, Marchetta A, Caramaschi P, Furlani L. Familial hypocalciuric hypercalcaemia revealed by chondrocalcinosis. Joint Bone Spine. 2009;76:708–10.PubMedCrossRefGoogle Scholar
  60. 60.
    Demedts M, Auwerx J, Goddeeris P, Bouillon R, Gyselen A, Lauweryns J. The inherited association of interstitial lung disease, hypocalciuric hypercalcemia, and defective granulocyte function. Am Rev Respir Dis. 1985;131:470–5.PubMedGoogle Scholar
  61. 61.
    Riccardi VM. Von Recklinghausen neurofibromatosis. N Engl J Med. 1981;305:1617–27.PubMedCrossRefGoogle Scholar
  62. 62.
    Neurofibromatosis: conference statement: National Institutes of Health Consensus Development Conference. Arch Neurol. 1988;45:575–8.Google Scholar
  63. 63.
    Evans DG, Baser ME, McGaughran J, Sharif S, Howard E, Moran A. Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet. 2002;39:311–4.PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    Zamora AC, Collard HR, Wolters PJ, Webb WR, King TE. Neurofibromatosis-associated lung disease: a case series and literature review. Eur Respir J. 2007;29:210–4.PubMedCrossRefGoogle Scholar
  65. 65.
    Massaro D, Katz S. Fibrosing alveolitis: its occurrence, roentgenographic, and pathologic features in von Recklinghausen’s neurofibromatosis. Am Rev Respir Dis. 1966;93:934–42.PubMedGoogle Scholar
  66. 66.
    Chang ET, Hu Wang A, Lin CB, Lee JJ, Yang GG. Pulmonary manifestation in neurofibromatosis type 1. Intern Med. 2007;46:527528.CrossRefGoogle Scholar
  67. 67.
    Riccardi VM, Lewis RA. Penetrance of von Recklinghausen neurofibromatosis: a distinction between predecessors and descendants. Am J Hum Genet. 1998;42:284–9.Google Scholar
  68. 68.
    Montani D, Coulet F, Girerd B, Eyries M, Bergot E, Mal H, et al. Pulmonary hypertension in patients with neurofibromatosis type I. Medicine. 2011;90:201–11.PubMedCrossRefGoogle Scholar
  69. 69.
    De Scheerder I, Elinck W, Van Renterghem D, Cuvelier C, Tasson J, Van der Straeten M. Desquamative interstitial neumonia and scar cancer of the lung complicating generalised neurofibromatosis. Eur J Respir Dis. 1984;65:623–6.PubMedGoogle Scholar
  70. 70.
    Shimizu Y, Tsuchiya S, Watanabe S, Saitoh R. von Recklinghausen’s disease with lung cancer derived from the wall of emphysematous bullae. Intern Med. 1994;33:167–71.PubMedCrossRefGoogle Scholar
  71. 71.
    Huie TJ, Schwarz MI. Miscellaneous interstitial lung diseases. In: Schwarz MI, King TE, editors. Interstitial Lung Disease. 5th ed. Shelton, CT: People’s Medical Publishing House. 2011:1095–1149.Google Scholar
  72. 72.
    Wert SE, Whitsett JA, Nogee LM. Genetic disorders of surfactant dysfunction. Pediatr Dev Pathol. 2009;12:253–74.PubMedCentralPubMedCrossRefGoogle Scholar
  73. 73.
    Nogee LM, Garnier G, Dietz HC, Singer L, Murphy AM, deMello DE, Colten HR. A mutation in the surfactant protein B gene responsible for fatal neonatal respiratory disease in multiple kindreds. J Clin Invest. 1994;93:1860–3.PubMedCentralPubMedCrossRefGoogle Scholar
  74. 74.
    Dunbar 3rd AE, Wert SE, Ikegami M, Whitsett JA, Hamvas A, White FV, Piedboeuf B, Jobin C, Guttentag S, Nogee LM. Prolonged survival in hereditary surfactant protein B (SP-B) deficiency associated with a novel splicing mutation. Pediatr Res. 2000;48:275–82.PubMedCrossRefGoogle Scholar
  75. 75.
    Cameron HS, Somaschini M, Carrera P, Hamvas A, Whitsett JA, Wert SE, Deutsch G, Nogee LM. A common mutation in the surfactant protein C gene associated with lung disease. J Pediatr. 2005;146:370–5.PubMedCrossRefGoogle Scholar
  76. 76.
    Mulugeta S, Nguyen V, Russo SJ, Muniswamy M, Beers MF. A surfactant protein C precursor protein BRICHOS domain mutation causes endoplasmic reticulum stress, proteasome dysfunction, and caspase 3 activation. Am J Respir Cell Mol Biol. 2005;32:521–30.PubMedCentralPubMedCrossRefGoogle Scholar
  77. 77.
    van Moorsel CH, van Oosterhout MF, Barlo NP, de Jong PA, van der Vis JJ, Ruven HJ, et al. Surfactant protein C mutations are the basis of a significant portion of adult familial pulmonary fibrosis in a dutch cohort. Am J Respir Crit Care Med. 2010;182:1419–25.PubMedCrossRefGoogle Scholar
  78. 78.
    Markart P, Ruppert C, Wygrecka M, Schmidt R, Korfei M, Harbach H, et al. Surfactant protein C mutations in sporadic forms of idiopathic interstitial pneumonias. Eur Respir J. 2007;29:134–7.PubMedCrossRefGoogle Scholar
  79. 79.
    Shulenin S, Nogee LM, Annilo T, Wert SE, Whitsett JA, Dean M. ABCA3 gene mutations in newborns with fatal surfactant deficiency. N Engl J Med. 2004;350:1296–303.PubMedCrossRefGoogle Scholar
  80. 80.
    Bullard JE, Wert SE, Whitsett JA, Dean M, Nogee LM. ABCA3 mutations associated with pediatric interstitial lung disease. Am J Respir Crit Care Med. 2005;172:1026–31.PubMedCentralPubMedCrossRefGoogle Scholar
  81. 81.
    Krude H, Schutz B, Biebermann H, von Moers A, Schnabel D, Neitzel H, et al. Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency. J Clin Invest. 2002;109:475–80.PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    Guillot L, Carre A, Szinnai G, Castanet M, Tron E, Jaubert F, et al. NKX2-1 mutations leading to surfactant protein promoter dysregulation cause interstitial lung disease in “Brain-Lung-Thyroid Syndrome”. Hum Mutat. 2010;31:E1146–62.PubMedCrossRefGoogle Scholar
  83. 83.
    Deutsch GH, Young LR, Deterding RR, Fan LL, Dell SD, Bean JA, et al. Diffuse lung disease in young children: application of a novel classification scheme. Am J Respir Crit Care Med. 2007;176:1120–8.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2015

Authors and Affiliations

  1. 1.Medical University Clinic, Canton Hospital Baselland, University of BaselLiestalSwitzerland

Personalised recommendations