OOA (Old Order Amish)
MEN (General Swiss-German Mennonite)
DGM (Dutch-German Mennonite)
HUT (Hutterite)

Inheritance: autosomal recessive
Genes: CFTR

CF

mucoviscidosis

Pancreatic insufficiency
Meconium ileus
Biliary cirrhosis
Infertility
Respiratory insufficiency

Cystic Fibrosis

Clinical Characteristics

General description (for patients):

Cystic fibrosis is a common genetic disease that affects multiple organs in the body, especially the lungs, liver, pancreas, intestinal tract and sweat glands.  Symptoms usually appear in the first year of life, although milder cases may not develop problems until midlife.  Clinical symptoms vary widely.  In the lungs, abnormally thick secretions create breathing problems and increase the risk of infections, and in the intestines the same problem leads to obstructions.  The digestion problems are compounded by decreased secretions of enzymes from the pancreas leading to fatty diarrhea and a deficiency in some vitamins.  The average lifespan of a person affected by cystic fibrosis is between 28 and 30 years of age.  Both males and females may be infertile.

Medical description:  

Cystic fibrosis is among the most widely occurring and well known of genetic disorders.  The pattern of development of CF and the severity of the symptoms vary greatly. Thick bronchial mucus production, together with a less competent immune system, results in respiratory difficulties and frequent lung infections.  In the digestive system,  meconium ileum is often seen while diminished secretion of pancreatic enzymes together with ductal obstruction may cause fatty diarrhea and lead to a deficiency in fat-soluble vitamins.  Biliary cirrhosis in some patients likely contributes as well.  Poor growth is a hallmark of CF.  Children with CF typically do not gain weight or height at the same rate as their peers. The causes are multi-factorial and include chronic lung infection, poor absorption of nutrients, and increased metabolic demand due to chronic illness.  Other symptoms include vomiting, gassiness, fever, cough, salty-tasting skin, abdominal pain and discomfort, rapid breathing, poor appetite, clubbing, hemoptysis, pneumothorax, cor pulmonale and rectal prolapse.  Diagnosis often can be determined prenatally through amniotic fluid testing for fetal intestinal enzymes, which are reduced in CF.  In newborns, an immunoreactive trypsinogen test for elevated trypsinogen can be used on dried blood spots. The common test for children and young adults is the electrolyte sweat test which measures electrolytes (sodium, potassium and chloride) in perspiration.  Puberty may be delayed while abnormal cervical mucous contributes to female infertility and absence of the vas deferens leads to the same result in males.

Genetics:

This condition is inherited as an autosomal recessive.  It is caused by mutations, of which there are many, in the cystic fibrosis gene (CFTR) located on chromosome 7 (7q31.2).  These mutations disrupt a protein called cystic fibrosis transmembrane conductance regulator (CFTR) that impacts ion channel (primarily chloride) gating specific to epithelial cells.
This disease is widespread among plain people and throughout the world.  Multiple mutations have been reported in many populations but only one (3434T>A) is found among Anabaptists.  An incidence of 1 in 569 live births among the Amish of Holmes County, OH, was reported in 1983 leading to an estimate of 0.042 for the gene frequency.  Curiously, not a single case was found among 4,448 live births in Geauga County, OH, in spite of the fact that the latter community was founded largely by settlers from Holmes County.

Cystic fibrosis was the disorder used for the first major population study on attitudes and reactions to genetic carrier testing among Amish/Mennonites and Hutterites.  Between 31% and 78% among all three groups approved of CF carrier testing and 14% to 78% approved of prenatal testing.  Not surprisingly, Mennonites were the most knowledgeable about recurrence risks, and the most desirous of knowing about their carrier testing results.  They were also the most likely to modify their reproductive behaviour based on the results. The Amish expressed a lot of uncertainty about whether they wished to know the results of carrier testing.  The vast majority of Amish opposed abortion for an affected fetus but a substantial number, especially siblings of affected children, indicated uncertainty about their decision.

Treatment:

There is no cure for CF.  Treatments are aimed at control of symptoms. High-energy foods, enzyme supplements, and vitamin and mineral supplements may be used in an attempt to provide the required nutrients. Daily pulmonary hygiene and breathing exercises help to prevent excessive mucus accumulation in the lungs.  Antibiotics and other medicines are used to control lung infections and inflammation.

Prognosis:

In most cases, CF leads to death at a relatively young age.  Average life expectancy is around 37.8 years according to the Cystic Fibrosis Foundation, although improvements in treatments mean a baby born today could expect to live longer.

Ancillary treatments and support:

Pulmonary hygiene, diet, good hygiene.

Specialists and speciality centers:

Pulmonologist, gastroenterologist, endocrinologist, pediatrician, infectious disease.

References:

Ratjen, F.:  Recent advances in cystic fibrosis. Paediat. Respir. Rev.  9: 144-148, 2008.  (Epub  2008 May 12)  PubMed ID: 18513677

Klinger, K.W.:  Cystic fibrosis in the Ohio Amish: gene frequency and founder effect.  Hum. Genet. 65: 94-98, 1983. PubMed ID: 6654341

Klinger, K., Horn, G.T., Stanislovitis, P., Schwartz, R.H., Fujiwara, T.M., and Morgan, K.:  Cystic fibrosis mutations in the Hutterite brethren.  Am. J. Hum. Genet. 46: 983-987, 1990.  PubMed ID: 2339696

Miller, S.R., and Schwartz, R.H.: Attitudes toward genetic testing of Amish, Mennonite, and Hutterite families with cystic fibrosis.  Am. J. Public Health.  82: 236-242, 1992. PubMed ID: 1739154

Zielenski, J., Fujiwara, T.M., Markiewicz, D., Paradis, A., Anacieto, A., Richards, B., Schwartz, R., Klinger, K., and Morgan, K.:  Identification of the M1101K mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and complete detection of cystic fibrosis mutations in the Hutterite population.  Am. J. Hum. Genet.  52: 609-615, 1993. PubMed ID: 7680525

Resources:

Cystic Fibrosis Foundation

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