Focus
Fibrosi cistica atipica
ATYPICAL CYSTIC FIBROSIS
C. Castellani
Marzo 2006 - pagg. 155 -173
Abstract
In recent years the ability to detect cystic fibrosis (CF) mutations has greatly expanded the clinical spectrum of the disease. In a rising number of patients an atypical, usually mild phenotype is found; in others a single clinical feature predominates. A diagnosis of CF is usually formulated following a positive sweat test, or the identification of disease-causing gene mutations, or the in vivo demonstration of the typical abnormalities in ion transport across the nasal or rectal epithelium. However, these same tests, although helpful, may prove inconclusive in individuals with such an unusual clinical presentation. Very little information is available about the possible long-term evolution of these non classical forms of disease.
Classificazione MeSH
Bibliografia
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3. Viviani L, Padoan R, Giglio L, Bossi A. The Italian registry for cystic fibrosis: what has changed in the last decade. Epidemiol Prev 2003; 27: 91-6.
4. Castellani C, Bonizzato A, Cabrini G, Mastella G. Newborn screening strategy for cystic fibrosis: a field study in an area with high allelic heterogeneity. Acta Paediatr 1997; 86: 497-502.
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8. Rendine S, Calafell F, Cappello N, et al. Genetic history of cystic fibrosis mutations in Italy. I. Regional distribution. Ann Hum Genet 1997;61:411-24.
9. Bonizzato A, Bisceglia L, Marigo M, et al. Analysis of the complete coding region of the CFTR gene in a cohort of CF patients from Northeastern Italy: identification of 90% of the mutations. Hum Genet 1995;95:397-402.
10. The Cystic Fibrosis Genotype-Phenotype Consortium. Correlation between genotype and phenotype in patients with cystic fibrosis. N Engl J Med 1993;329:1308-13.
11. Anguiano A, Oates RD, Amos JA, et al. Congenital absence of the vas deferens. A primarily genital form of cystic fibrosis. JAMA 1992; 267:1704-97.
12. Chillon M, Casals T, Mercier B, et al. Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. N Engl J Med 1995;332:1475-80.
13. Cohn JA, Friedman KJ, Noone PG, Knowles MR, Silverman LM, Jowell PS. Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis. N Engl J Med 1998;339:635-8.
14. Castellani C, Gomez Lira M, Frulloni L, et al. Analysis of the entire coding region of the cystic fibrosis transmembrane regulator gene in idiopathic pancreatitis. Hum Mutation. 2001 Mutation in brief #436 Online.
15. Ranieri E, Ryall RG, Lewis BD, et al. Neonatal screening for cystic fibrosis using immunoreactive trypsinogen and direct gene analysis. BMJ 1991; 302:1237-40.
16. Laroche D, Travert G. Abnormal frequency of ΔF508 in neonatal transitory hypertrypsinaemia. Lancet 1991;337:55.
17. Lecoq I, Brouard J, Laroche D, et al. Blood immunoreactive trypsinogen concentrations are genetically determined in healthy and cystic fibrosis newborns. Acta Paediatr 1999;88:338-41.
18. Castellani C, Picci L, Scarpa M, et al. Cystic fibrosis carriers have higher neonatal immunoreactive trypsinogen values than non-carriers. Am J Med Genet 2005;135A:141-4.
19. Castellani C, Benetazzo MG, Tamanini A, Begnini A, Mastella G, Pignatti PF. Analysis of the entire coding region of the cystic fibrosis transmembrane regulator gene in neonatal hypertrypsinemia with normal sweat test. J Med Genet 2001;38:202-5.
20. Pignatti PF, Bombieri C, Marigo C, Benetazzo M, Luisetti M. Increased incidence of cystic fibrosis gene mutations in adults with disseminated bronchiectasis. Hum Mol Genet 1995;4:635-9.
21. Wang X, Moylan B, Leopold DA, et al. Mutation in the gene responsible for cystic fibrosis and predisposition to chronic rhinosinusitis in the general population. JAMA 2000;284:1814-9.
22. Miller PW, Hamosh A, Macek M Jr, et al. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in allergic bronchopulmonary aspergillosis. Am J Hum Genet 1996;59:45-51.
23. Rosenstein BJ, Cutting GR, for the Cystic Fibrosis Foundation Consensus Panel. The diagnosis of cystic fibrosis: a consensus statement. J Pediatr 1998;132:589-95.
24. Farrell PM, Koscik RE. Sweat chloride concentrations in infants homozygous or heterozygous for F508 cystic fibrosis. Pediatrics 1996;97:524-8.
25. Groman JD, Karczeski B, Sheridan M, Robinson TE, Fallin MD, Cutting GR. Phenotypic and genetic characterization of patients with features of “nonclassic” forms of cystic fibrosis. J Pediatr 2005; 146:675-80.
26. Ravnik-Glavac M, Atkinson A, Glavac D, Dean M. DHPLC screening of cystic fibrosis gene mutations. Hum Mut 2002;19:374-83.
27. Pradal U, Castellani C, Delmarco A, Mastella G. Nasal potential difference in congenital bilateral absence of the vas deferens. Am J Respir Crit Care Med 1998;158:896-901.
28. Groman JD, Meyer ME, Wilmott RW, Zeitlin PL, Cutting GR. Variant cystic fibrosis phenotypes in the absence of CFTR mutations. N Engl J Med 2003;347:401-7.
29. Boyle MP. Nonclassic cystic fibrosis and CFTRrelated diseases. Curr Opin Pulm Med 2003;9:498- 503.
2. Frederiksen B, Lanng S, Kock C, Hoiby N. Improved survival in the Danish center-treated cystic fibrosis patients: results of aggressive treatment. Pediatr Pulmonol 1996; 21: 153-8.
3. Viviani L, Padoan R, Giglio L, Bossi A. The Italian registry for cystic fibrosis: what has changed in the last decade. Epidemiol Prev 2003; 27: 91-6.
4. Castellani C, Bonizzato A, Cabrini G, Mastella G. Newborn screening strategy for cystic fibrosis: a field study in an area with high allelic heterogeneity. Acta Paediatr 1997; 86: 497-502.
5. Corbetta C, Seia M, Bassotti A, Ambrosioni A, Giunta A, Padoan R. Screening for cystic fibrosis in newborn infants: results of a pilot programme based on a two tier protocol (IRT/DNA/IRT) in the Italian population. J Med Screen 2002;9:60-63.
6. Castellani C. Dieci anni dalla scoperta del gene della fibrosi cistica: implicazioni cliniche. Aggiornamenti di fisiopatologia e terapia in pediatria, 2000;10:14-21.
7. Cystic Fibrosis Genetic Consortium. Cystic Fibrosis Genetic Data Base. URL: htpp://www.genet. sickkids.on.ca/cftr.
8. Rendine S, Calafell F, Cappello N, et al. Genetic history of cystic fibrosis mutations in Italy. I. Regional distribution. Ann Hum Genet 1997;61:411-24.
9. Bonizzato A, Bisceglia L, Marigo M, et al. Analysis of the complete coding region of the CFTR gene in a cohort of CF patients from Northeastern Italy: identification of 90% of the mutations. Hum Genet 1995;95:397-402.
10. The Cystic Fibrosis Genotype-Phenotype Consortium. Correlation between genotype and phenotype in patients with cystic fibrosis. N Engl J Med 1993;329:1308-13.
11. Anguiano A, Oates RD, Amos JA, et al. Congenital absence of the vas deferens. A primarily genital form of cystic fibrosis. JAMA 1992; 267:1704-97.
12. Chillon M, Casals T, Mercier B, et al. Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. N Engl J Med 1995;332:1475-80.
13. Cohn JA, Friedman KJ, Noone PG, Knowles MR, Silverman LM, Jowell PS. Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis. N Engl J Med 1998;339:635-8.
14. Castellani C, Gomez Lira M, Frulloni L, et al. Analysis of the entire coding region of the cystic fibrosis transmembrane regulator gene in idiopathic pancreatitis. Hum Mutation. 2001 Mutation in brief #436 Online.
15. Ranieri E, Ryall RG, Lewis BD, et al. Neonatal screening for cystic fibrosis using immunoreactive trypsinogen and direct gene analysis. BMJ 1991; 302:1237-40.
16. Laroche D, Travert G. Abnormal frequency of ΔF508 in neonatal transitory hypertrypsinaemia. Lancet 1991;337:55.
17. Lecoq I, Brouard J, Laroche D, et al. Blood immunoreactive trypsinogen concentrations are genetically determined in healthy and cystic fibrosis newborns. Acta Paediatr 1999;88:338-41.
18. Castellani C, Picci L, Scarpa M, et al. Cystic fibrosis carriers have higher neonatal immunoreactive trypsinogen values than non-carriers. Am J Med Genet 2005;135A:141-4.
19. Castellani C, Benetazzo MG, Tamanini A, Begnini A, Mastella G, Pignatti PF. Analysis of the entire coding region of the cystic fibrosis transmembrane regulator gene in neonatal hypertrypsinemia with normal sweat test. J Med Genet 2001;38:202-5.
20. Pignatti PF, Bombieri C, Marigo C, Benetazzo M, Luisetti M. Increased incidence of cystic fibrosis gene mutations in adults with disseminated bronchiectasis. Hum Mol Genet 1995;4:635-9.
21. Wang X, Moylan B, Leopold DA, et al. Mutation in the gene responsible for cystic fibrosis and predisposition to chronic rhinosinusitis in the general population. JAMA 2000;284:1814-9.
22. Miller PW, Hamosh A, Macek M Jr, et al. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in allergic bronchopulmonary aspergillosis. Am J Hum Genet 1996;59:45-51.
23. Rosenstein BJ, Cutting GR, for the Cystic Fibrosis Foundation Consensus Panel. The diagnosis of cystic fibrosis: a consensus statement. J Pediatr 1998;132:589-95.
24. Farrell PM, Koscik RE. Sweat chloride concentrations in infants homozygous or heterozygous for F508 cystic fibrosis. Pediatrics 1996;97:524-8.
25. Groman JD, Karczeski B, Sheridan M, Robinson TE, Fallin MD, Cutting GR. Phenotypic and genetic characterization of patients with features of “nonclassic” forms of cystic fibrosis. J Pediatr 2005; 146:675-80.
26. Ravnik-Glavac M, Atkinson A, Glavac D, Dean M. DHPLC screening of cystic fibrosis gene mutations. Hum Mut 2002;19:374-83.
27. Pradal U, Castellani C, Delmarco A, Mastella G. Nasal potential difference in congenital bilateral absence of the vas deferens. Am J Respir Crit Care Med 1998;158:896-901.
28. Groman JD, Meyer ME, Wilmott RW, Zeitlin PL, Cutting GR. Variant cystic fibrosis phenotypes in the absence of CFTR mutations. N Engl J Med 2003;347:401-7.
29. Boyle MP. Nonclassic cystic fibrosis and CFTRrelated diseases. Curr Opin Pulm Med 2003;9:498- 503.
Corrispondenza: carlo.castellani@azosp.vr.it