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Cystic fibrosis(CF)

MedGen UID:
41393
Concept ID:
C0010674
Disease or Syndrome
Synonyms: CF; Classic Cystic Fibrosis; Mucoviscidosis
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: HPO
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
SNOMED CT: Cystic fibrosis (190905008); CF - Cystic fibrosis (190905008); Fibrocystic disease (190905008); CF (190905008); Mucoviscidosis (190905008)
 
Genes (locations): CFTR (7q31.2); TGFB1 (19q13.2)
OMIM®: 219700
Orphanet: ORPHA586

Disease characteristics

Excerpted from the GeneReview: CFTR-Related Disorders
CFTR-related disorders include cystic fibrosis (CF) and congenital absence of the vas deferens (CAVD). Cystic fibrosis affects epithelia of the respiratory tract, exocrine pancreas, intestine, male genital tract, hepatobiliary system, and exocrine sweat glands, resulting in complex multisystem disease. Pulmonary disease is the major cause of morbidity and mortality in CF. Affected individuals have lower airway inflammation and chronic endobronchial infection, progressing to end-stage lung disease characterized by extensive airway damage (bronchiectasis, cysts, and abscesses) and fibrosis of lung parenchyma. Meconium ileus occurs at birth in 15%-20% of newborns with CF. Pancreatic insufficiency with malabsorption occurs in the great majority of individuals with CF. More than 95% of males with CF are infertile as a result of azoospermia caused by absent, atrophic, or fibrotic Wolffian duct structures. CAVD occurs in men without pulmonary or gastrointestinal manifestations of CF. Affected men have azoospermia and are thus infertile. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Characteristics  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Samuel M Moskowitz  |  James F Chmiel  |  Darci L Sternen, et. al.   view full author information

Additional descriptions

From OMIM
Formerly known as cystic fibrosis of the pancreas, this entity has increasingly been labeled simply 'cystic fibrosis.' Manifestations relate not only to the disruption of exocrine function of the pancreas but also to intestinal glands (meconium ileus), biliary tree (biliary cirrhosis), bronchial glands (chronic bronchopulmonary infection with emphysema), and sweat glands (high sweat electrolyte with depletion in a hot environment). Infertility occurs in males and females. For discussion of a phenotype consisting of bronchiectasis with or without elevated sweat chloride caused by mutation in the genes encoding the 3 subunits of the epithelial sodium channel, see BESC1 (211400).  http://www.omim.org/entry/219700
From GHR
Cystic fibrosis is an inherited disease characterized by the buildup of thick, sticky mucus that can damage many of the body's organs. The disorder's most common signs and symptoms include progressive damage to the respiratory system and chronic digestive system problems. The features of the disorder and their severity varies among affected individuals. Mucus is a slippery substance that lubricates and protects the linings of the airways, digestive system, reproductive system, and other organs and tissues. In people with cystic fibrosis, the body produces mucus that is abnormally thick and sticky. This abnormal mucus can clog the airways, leading to severe problems with breathing and bacterial infections in the lungs. These infections cause chronic coughing, wheezing, and inflammation. Over time, mucus buildup and infections result in permanent lung damage, including the formation of scar tissue (fibrosis) and cysts in the lungs. Most people with cystic fibrosis also have digestive problems. Some affected babies have meconium ileus, a blockage of the intestine that occurs shortly after birth. Other digestive problems result from a buildup of thick, sticky mucus in the pancreas. The pancreas is an organ that produces insulin (a hormone that helps control blood sugar levels). It also makes enzymes that help digest food. In people with cystic fibrosis, mucus blocks the ducts of the pancreas, reducing the production of insulin and preventing digestive enzymes from reaching the intestines to aid digestion. Problems with digestion can lead to diarrhea, malnutrition, poor growth, and weight loss. In adolescence or adulthood, a shortage of insulin can cause a form of diabetes known as cystic fibrosis-related diabetes mellitus (CFRDM). Cystic fibrosis used to be considered a fatal disease of childhood. With improved treatments and better ways to manage the disease, many people with cystic fibrosis now live well into adulthood. Adults with cystic fibrosis experience health problems affecting the respiratory, digestive, and reproductive systems. Most men with cystic fibrosis have congenital bilateral absence of the vas deferens (CBAVD), a condition in which the tubes that carry sperm (the vas deferens) are blocked by mucus and do not develop properly. Men with CBAVD are unable to father children (infertile) unless they undergo fertility treatment. Women with cystic fibrosis may experience complications in pregnancy.  http://ghr.nlm.nih.gov/condition/cystic-fibrosis

Clinical features

Failure to thrive
MedGen UID:
115900
Concept ID:
C0231246
Sign or Symptom
Slower than normal rate of weight increase.
Hypercalciuria
MedGen UID:
505127
Concept ID:
CN001948
Finding
Male infertility
MedGen UID:
505497
Concept ID:
CN002937
Finding
Malabsorption
MedGen UID:
368423
Concept ID:
C1963165
Finding
Abnormality of the pancreas
MedGen UID:
427891
Concept ID:
CN001576
Finding
An abnormality of the pancreas.
Exocrine pancreatic insufficiency
MedGen UID:
504939
Concept ID:
CN001582
Finding
Impaired function of the exocrine pancreas associated with a reduced ability to digest foods because of lack of digestive enzymes.
Rectal prolapse
MedGen UID:
505063
Concept ID:
CN001840
Finding
Protrusion of the rectal mucous membrane through the anus.
Hepatomegaly
MedGen UID:
505165
Concept ID:
CN002031
Finding
Abnormally increased size of the liver.
Biliary cirrhosis
MedGen UID:
505295
Concept ID:
CN002375
Finding
Progressive destruction of the small-to-medium bile ducts of the intrahepatic biliary tree, which leads to progressive cholestasis and often end-stage liver disease.
Meconium ileus
MedGen UID:
446599
Concept ID:
CN003899
Finding
Obstruction of the intestine due to abnormally thick meconium.
Cor pulmonale
MedGen UID:
504890
Concept ID:
CN001501
Finding
Right-sided heart failure resulting from chronic hypertension in the pulmonary arteries and right ventricle.
Decreased antibody level in blood
MedGen UID:
428063
Concept ID:
CN003814
Finding
An abnormally decreased level of immunoglobulin in blood.
Elevated sweat chloride
MedGen UID:
347278
Concept ID:
C1856646
Finding
Dehydration
MedGen UID:
776589
Concept ID:
C2712335
Finding
Hypercalciuria
MedGen UID:
505127
Concept ID:
CN001948
Finding
Decreased antibody level in blood
MedGen UID:
428063
Concept ID:
CN003814
Finding
An abnormally decreased level of immunoglobulin in blood.
Recurrent respiratory infections
MedGen UID:
400943
Concept ID:
C1866203
Finding
Recurrent bronchopulmonary infections
MedGen UID:
488990
Concept ID:
C2169795
Finding
Asthma
MedGen UID:
505101
Concept ID:
CN001900
Finding
Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing.
Bronchiectasis
MedGen UID:
505109
Concept ID:
CN001911
Finding
Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways.
Pulmonary fibrosis
MedGen UID:
505156
Concept ID:
CN002000
Finding
Replacement of normal lung tissues are progressively replaced by fibroblasts and collagen.
Chronic lung disease
MedGen UID:
505923
Concept ID:
CN005686
Finding
According to the definitions of the American and British Thoracic Societies, including pulmonary functional tests, X-rays, and CT scans for items such as fibrosis, bronchiectasis, bullae, emphysema, nodular or lymphomatous abnormalities.
Recurrent pneumonia
MedGen UID:
505924
Concept ID:
CN005690
Finding
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
Recurrent respiratory infections
MedGen UID:
400943
Concept ID:
C1866203
Finding
Recurrent bronchopulmonary infections
MedGen UID:
488990
Concept ID:
C2169795
Finding
Asthma
MedGen UID:
505101
Concept ID:
CN001900
Finding
Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing.
Decreased antibody level in blood
MedGen UID:
428063
Concept ID:
CN003814
Finding
An abnormally decreased level of immunoglobulin in blood.
Recurrent pneumonia
MedGen UID:
505924
Concept ID:
CN005690
Finding
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.

Professional guidelines

PubMed

Delatycki MB, Burke J, Christie L, Collins F, Gabbett M, George P, Haan E, Ioannou L, Martin N, McKenzie F, O'Leary P, Scoble-Williams N, Turner G, Massie J; Human Genetics Society of Australasia
Twin Res Hum Genet 2014 Dec;17(6):578-83. doi: 10.1017/thg.2014.65. PMID: 25431289
Clancy JP, Johnson SG, Yee SW, McDonagh EM, Caudle KE, Klein TE, Cannavo M, Giacomini KM; Clinical Pharmacogenetics Implementation Consortium
Clin Pharmacol Ther 2014 Jun;95(6):592-7. Epub 2014 Mar 5 doi: 10.1038/clpt.2014.54. [Epub ahead of print] PMID: 24598717Free PMC Article
Langfelder-Schwind E, Karczeski B, Strecker MN, Redman J, Sugarman EA, Zaleski C, Brown T, Keiles S, Powers A, Ghate S, Darrah R
J Genet Couns 2014 Feb;23(1):5-15. Epub 2013 Sep 7 doi: 10.1007/s10897-013-9636-9. [Epub ahead of print] PMID: 24014130
Centers for Disease Control and Prevention (CDC)
MMWR Recomm Rep 2012 Apr 6;61(RR-2):1-44. PMID: 22475884
American College of Obstetricians and Gynecologists Committee on Genetics
Obstet Gynecol 2011 Apr;117(4):1028-31. doi: 10.1097/AOG.0b013e31821922c2. PMID: 21422883
Flume PA, Mogayzel PJ Jr, Robinson KA, Rosenblatt RL, Quittell L, Marshall BC; Clinical Practice Guidelines for Pulmonary Therapies Committee; Cystic Fibrosis Foundation Pulmonary Therapies Committee
Am J Respir Crit Care Med 2010 Aug 1;182(3):298-306. doi: 10.1164/rccm.201002-0157OC. PMID: 20675678
Sermet-Gaudelus I, Mayell SJ, Southern KW; European Cystic Finrosis Society (ECFS), Neonatal Screening Working Group
J Cyst Fibros 2010 Sep;9(5):323-9. doi: 10.1016/j.jcf.2010.04.008. PMID: 20605539
Cystic Fibrosis Foundation, Borowitz D, Robinson KA, Rosenfeld M, Davis SD, Sabadosa KA, Spear SL, Michel SH, Parad RB, White TB, Farrell PM, Marshall BC, Accurso FJ
J Pediatr 2009 Dec;155(6 Suppl):S73-93. doi: 10.1016/j.jpeds.2009.09.001. PMID: 19914445
Cystic Fibrosis Foundation, Borowitz D, Parad RB, Sharp JK, Sabadosa KA, Robinson KA, Rock MJ, Farrell PM, Sontag MK, Rosenfeld M, Davis SD, Marshall BC, Accurso FJ
J Pediatr 2009 Dec;155(6 Suppl):S106-16. doi: 10.1016/j.jpeds.2009.09.003. PMID: 19914443
ACOG Committee on Genetics
Obstet Gynecol 2009 Oct;114(4):950-3. doi: 10.1097/AOG.0b013e3181bd12f4. PMID: 19888064
Gross SJ, Pletcher BA, Monaghan KG; Professional Practice and Guidelines Committee
Genet Med 2008 Jan;10(1):54-6. doi: 10.1097/GIM.0b013e31815f247c. PMID: 18197057Free PMC Article
Langfelder-Schwind E, Kloza E, Sugarman E, Pettersen B, Brown T, Jensen K, Marcus S, Redman J; National Society of Genetic Counselors Subcommittee on Cystic Fibrosis Carrier Testing
J Genet Couns 2005 Feb;14(1):1-15. doi: 10.1007/s10897-005-1496-5. PMID: 15789152
Watson MS, Cutting GR, Desnick RJ, Driscoll DA, Klinger K, Mennuti M, Palomaki GE, Popovich BW, Pratt VM, Rohlfs EM, Strom CM, Richards CS, Witt DR, Grody WW
Genet Med 2004 Sep-Oct;6(5):387-91. doi: 10.109701.GIM.0000139506.11694.7C. PMID: 15371902Free PMC Article
Richards CS, Bradley LA, Amos J, Allitto B, Grody WW, Maddalena A, McGinnis MJ, Prior TW, Popovich BW, Watson MS, Palomaki GE
Genet Med 2002 Sep-Oct;4(5):379-91. doi: 10.109700125817-200209000-00010. PMID: 12394352
Bethesda (MD): American College of Medical Genetics; 2001-; PMID: 21938795Books & Documents
Grody WW, Cutting GR, Klinger KW, Richards CS, Watson MS, Desnick RJ; Subcommittee on Cystic Fibrosis Screening, Accreditation of Genetic Services Committee, ACMG. American College of Medical Genetics
Genet Med 2001 Mar-Apr;3(2):149-54. doi: 10.109700125817-200103000-00010. PMID: 11280952

External

DailyMed Drug Label, KALYDECO, 2012

Suggested Reading

PubMed

Wainwright CE, Elborn JS, Ramsey BW, Marigowda G, Huang X, Cipolli M, Colombo C, Davies JC, De Boeck K, Flume PA, Konstan MW, McColley SA, McCoy K, McKone EF, Munck A, Ratjen F, Rowe SM, Waltz D, Boyle MP; TRAFFIC Study Group; TRANSPORT Study Group
N Engl J Med 2015 Jul 16;373(3):220-31. Epub 2015 May 17 doi: 10.1056/NEJMoa1409547. [Epub ahead of print] PMID: 25981758
Accurso FJ, Rowe SM, Clancy JP, Boyle MP, Dunitz JM, Durie PR, Sagel SD, Hornick DB, Konstan MW, Donaldson SH, Moss RB, Pilewski JM, Rubenstein RC, Uluer AZ, Aitken ML, Freedman SD, Rose LM, Mayer-Hamblett N, Dong Q, Zha J, Stone AJ, Olson ER, Ordoñez CL, Campbell PW, Ashlock MA, Ramsey BW
N Engl J Med 2010 Nov 18;363(21):1991-2003. doi: 10.1056/NEJMoa0909825. PMID: 21083385Free PMC Article

Recent clinical studies

Etiology

Abbott J, Morton AM, Hurley MA, Conway SP
BMJ Open 2015 May 19;5(5):e007418. doi: 10.1136/bmjopen-2014-007418. PMID: 25991453Free PMC Article
Wainwright CE, Elborn JS, Ramsey BW, Marigowda G, Huang X, Cipolli M, Colombo C, Davies JC, De Boeck K, Flume PA, Konstan MW, McColley SA, McCoy K, McKone EF, Munck A, Ratjen F, Rowe SM, Waltz D, Boyle MP; TRAFFIC Study Group; TRANSPORT Study Group
N Engl J Med 2015 Jul 16;373(3):220-31. Epub 2015 May 17 doi: 10.1056/NEJMoa1409547. [Epub ahead of print] PMID: 25981758
Bodewes FA, Verkade HJ, Taminiau JA, Borowitz D, Wilschanski M; Working group C​ystic Fibrosis and Pancreatic Disease of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN)
J Cyst Fibros 2015 Mar;14(2):169-77. Epub 2015 Feb 10 doi: 10.1016/j.jcf.2015.01.006. [Epub ahead of print] PMID: 25677689
Wagener JS, Elkin EP, Pasta DJ, Schechter MS, Konstan MW, Morgan WJ; Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis
J Cyst Fibros 2015 May;14(3):376-83. Epub 2014 Dec 9 doi: 10.1016/j.jcf.2014.11.008. [Epub ahead of print] PMID: 25498960
Megías MC, Albarrán OG, Vasco PG, Ferreiro AL, Carro LM
Diabetes Metab Syndr 2015 Jan-Mar;9(1):1-6. Epub 2014 Oct 24 doi: 10.1016/j.dsx.2014.09.016. [Epub ahead of print] PMID: 25450813

Diagnosis

Ren CL, Fink AK, Petren K, Borowitz DS, McColley SA, Sanders DB, Rosenfeld M, Marshall BC
Pediatrics 2015 Jun;135(6):e1386-92. Epub 2015 May 11 doi: 10.1542/peds.2014-3698. [Epub ahead of print] PMID: 25963008
Esmaeili Dooki MR, Tabaripour R, Rahimi R, Akhavan-Niaki H
Gene 2015 Jun 15;564(2):193-6. Epub 2015 Mar 28 doi: 10.1016/j.gene.2015.03.056. [Epub ahead of print] PMID: 25824381
Bodewes FA, Verkade HJ, Taminiau JA, Borowitz D, Wilschanski M; Working group C​ystic Fibrosis and Pancreatic Disease of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN)
J Cyst Fibros 2015 Mar;14(2):169-77. Epub 2015 Feb 10 doi: 10.1016/j.jcf.2015.01.006. [Epub ahead of print] PMID: 25677689
Megías MC, Albarrán OG, Vasco PG, Ferreiro AL, Carro LM
Diabetes Metab Syndr 2015 Jan-Mar;9(1):1-6. Epub 2014 Oct 24 doi: 10.1016/j.dsx.2014.09.016. [Epub ahead of print] PMID: 25450813
van der Ploeg CP, van den Akker-van Marle ME, Vernooij-van Langen AM, Elvers LH, Gille JJ, Verkerk PH, Dankert-Roelse JE; CHOPIN study group
J Cyst Fibros 2015 Mar;14(2):194-202. Epub 2014 Sep 10 doi: 10.1016/j.jcf.2014.08.007. [Epub ahead of print] PMID: 25213034

Therapy

Brodsky JL, Frizzell RA
Cell 2015 Sep 24;163(1):17. doi: 10.1016/j.cell.2015.09.003. PMID: 26406363
Abbott J, Morton AM, Hurley MA, Conway SP
BMJ Open 2015 May 19;5(5):e007418. doi: 10.1136/bmjopen-2014-007418. PMID: 25991453Free PMC Article
Wainwright CE, Elborn JS, Ramsey BW, Marigowda G, Huang X, Cipolli M, Colombo C, Davies JC, De Boeck K, Flume PA, Konstan MW, McColley SA, McCoy K, McKone EF, Munck A, Ratjen F, Rowe SM, Waltz D, Boyle MP; TRAFFIC Study Group; TRANSPORT Study Group
N Engl J Med 2015 Jul 16;373(3):220-31. Epub 2015 May 17 doi: 10.1056/NEJMoa1409547. [Epub ahead of print] PMID: 25981758
Megías MC, Albarrán OG, Vasco PG, Ferreiro AL, Carro LM
Diabetes Metab Syndr 2015 Jan-Mar;9(1):1-6. Epub 2014 Oct 24 doi: 10.1016/j.dsx.2014.09.016. [Epub ahead of print] PMID: 25450813
Vreede CL, Berkhout MC, Sprij AJ, Fokkens WJ, Heijerman HG
J Cyst Fibros 2015 May;14(3):412-3. Epub 2014 Aug 26 doi: 10.1016/j.jcf.2014.07.013. [Epub ahead of print] PMID: 25169789

Prognosis

Abbott J, Morton AM, Hurley MA, Conway SP
BMJ Open 2015 May 19;5(5):e007418. doi: 10.1136/bmjopen-2014-007418. PMID: 25991453Free PMC Article
Thaker V, Haagensen AL, Carter B, Fedorowicz Z, Houston BW
Cochrane Database Syst Rev 2015 May 20;5:CD008901. doi: 10.1002/14651858.CD008901.pub3. PMID: 25991406
Wainwright CE, Elborn JS, Ramsey BW, Marigowda G, Huang X, Cipolli M, Colombo C, Davies JC, De Boeck K, Flume PA, Konstan MW, McColley SA, McCoy K, McKone EF, Munck A, Ratjen F, Rowe SM, Waltz D, Boyle MP; TRAFFIC Study Group; TRANSPORT Study Group
N Engl J Med 2015 Jul 16;373(3):220-31. Epub 2015 May 17 doi: 10.1056/NEJMoa1409547. [Epub ahead of print] PMID: 25981758
Ren CL, Fink AK, Petren K, Borowitz DS, McColley SA, Sanders DB, Rosenfeld M, Marshall BC
Pediatrics 2015 Jun;135(6):e1386-92. Epub 2015 May 11 doi: 10.1542/peds.2014-3698. [Epub ahead of print] PMID: 25963008
Wagener JS, Elkin EP, Pasta DJ, Schechter MS, Konstan MW, Morgan WJ; Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis
J Cyst Fibros 2015 May;14(3):376-83. Epub 2014 Dec 9 doi: 10.1016/j.jcf.2014.11.008. [Epub ahead of print] PMID: 25498960

Clinical prediction guides

Chauvet S, Traboulsi W, Thevenon L, Kouadri A, Feige JJ, Camara B, Alfaidy N, Benharouga M
Am J Physiol Lung Cell Mol Physiol 2015 Aug 1;309(3):L314-22. Epub 2015 Jun 5 doi: 10.1152/ajplung.00382.2014. [Epub ahead of print] PMID: 26047640
Abbott J, Morton AM, Hurley MA, Conway SP
BMJ Open 2015 May 19;5(5):e007418. doi: 10.1136/bmjopen-2014-007418. PMID: 25991453Free PMC Article
Wainwright CE, Elborn JS, Ramsey BW, Marigowda G, Huang X, Cipolli M, Colombo C, Davies JC, De Boeck K, Flume PA, Konstan MW, McColley SA, McCoy K, McKone EF, Munck A, Ratjen F, Rowe SM, Waltz D, Boyle MP; TRAFFIC Study Group; TRANSPORT Study Group
N Engl J Med 2015 Jul 16;373(3):220-31. Epub 2015 May 17 doi: 10.1056/NEJMoa1409547. [Epub ahead of print] PMID: 25981758
Ren CL, Fink AK, Petren K, Borowitz DS, McColley SA, Sanders DB, Rosenfeld M, Marshall BC
Pediatrics 2015 Jun;135(6):e1386-92. Epub 2015 May 11 doi: 10.1542/peds.2014-3698. [Epub ahead of print] PMID: 25963008
Wagener JS, Elkin EP, Pasta DJ, Schechter MS, Konstan MW, Morgan WJ; Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis
J Cyst Fibros 2015 May;14(3):376-83. Epub 2014 Dec 9 doi: 10.1016/j.jcf.2014.11.008. [Epub ahead of print] PMID: 25498960

Recent systematic reviews

Thaker V, Haagensen AL, Carter B, Fedorowicz Z, Houston BW
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Morton A, Wolfe S
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Waters V, Ratjen F
Cochrane Database Syst Rev 2015 Mar 5;3:CD009528. doi: 10.1002/14651858.CD009528.pub3. PMID: 25741986
Chopra R, Paul L, Manickam R, Aronow WS, Maguire GP
Expert Opin Drug Saf 2015 Mar;14(3):401-11. Epub 2015 Jan 20 doi: 10.1517/14740338.2015.994503. [Epub ahead of print] PMID: 25604518

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