Genetic Transmission of Cystic Fibrosis and the Effects of this Condition Essay
Cystic fibrosis is one of the most prevalent autosomal recessive disorders - Genetic Transmission of Cystic Fibrosis and the Effects of this Condition Essay introduction. Its transmission is widely accepted as monogenic, although recent studies have implicated other genetic modifiers in its development. Even more diversified is the wide array of signs and symptoms that the condition manifests as.
Genetic Transmission of Cystic Fibrosis and the Effects of this Condition
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Cystic fibrosis is one of the most pervasive genetic disorders. It is a recessive autosomal condition caused by abnormalities in the synthesis and modification of a transmembrane protein. The key pathological characteristic is the presence of exceedingly viscous exocrine secretions in the lumens of the lung, intestine, and the biliary and reproductive tracts. Ultimately leading to obstruction, these secretions cause most of the clinical features of this disorder (Kumar & Maitra, 2004, p.489).
The essential genetic defect that causes cystic fibrosis is a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7 (Boucher, 2007, p.1543). The multi-domain protein encoded by this gene has a transmembrane domain which forms a chloride channel across the epithelia of various tracts; a key factor in controlling electrolyte and water transport, and hence viscosity, of the secretions in the lumen. Although 800 different mutations have been recognized (Kumar & Maitra, 2004, p.491), the most abundant mutation associated with this condition is a deletion of 3 base pairs resulting in a loss of one amino acid, namely phenylalanine (Boucher, 2007, p. 1543).
As it is a recessive disorder, non symptomatic carriers, i.e. heterozygous individuals have a 25 % chance of producing an offspring with this disorder. The chances are increased to 50% when a normal individual has children with an affected person. As is the case with the transmission of any recessive trait, a vast majority of sufferers are children of phenotypically normal parents; and the offspring of a normal and affected person is usually normal (Roberts & Pembrey, p. 55).
Widely having been considered a monogenic disorder, evidence to the contrary has recently surfaced. Polymorphisms in mannose-binding lectin, an immunologically important modifier, have been implicated in increasing the risk of end stage lung disease and incomplete recovery after bacterial invasions. A modifier locus has been mapped on chromosome 19 which affects the degree and incidence of meconium ileus (cited in Kumar & Maitra, p. 492).
Effects of this Condition
Cystic fibrosis tends to be highly variable in its clinical presentation. The stagnant and viscous secretions of the gastrointestinal tract cause intestinal obstruction within a day of birth in 18% of patients. This is clinically manifested by abdominal distension, vomiting, and difficulty in defecation; collectively called meconium ileus. But the commonest presentation of this disorder is respiratory distress due to alveolar obstruction leading to chronic lung infections. Pseudomonas aeruginosa seems to inhabit the lungs of 4 in every 5 patients of classic cystic fibrosis by the age of 18 (cited in Kumar & Maitra, p. 495). The increased tissue resistance of the lungs may also result in right heart failure, a condition known as cor pulmonale.
A large proportion of patients suffer from the adverse effects of exocrine pancreatic insufficiency. This has several injurious consequences including the inadequate absorption of fat and protein, persistent diarrhea, little weight gain and failure to thrive. Fat malabsorption can result in a deficiency of fat-soluble vitamins and impaired protein absorption may lead to reduced plasma protein levels and generalized edema. A widespread destruction of the pancreas can result in impairment of the endocrine pancreas as well, and hence, diabetes mellitus (Welsh, 2007).
With increasing use of antibiotics against lung infections, improved monitoring and better life expectancy of patients, a set of hepatic symptoms has been unveiled, previously masked by respiratory and pancreatic complications. Liver disease associated with cystic fibrosis is now one of the leading causes of mortality amongst patients of this disease. In fact, hepatomegaly is a clinically silent symptom in almost a third of all sufferers (Kumar & Maitra, 2004, p.495). Patients may present with pain of the abdomen and sudden onset jaundice due to the inspissated secretions and cholelithiasis. A minority of such patients may also develop cirrhosis.
The onset of puberty is delayed in all patients. Almost all of the male patients present with infertility, probably an outcome of the impaired fluid secretion. Women present with condensed cervical mucus, causing a drop in fertility (Ryan, 2006, p.119).
Boucher, R. (2007). Cystic Fibrosis. In Harrison’s Principles of Medicine, 16th Edition (p. 1543). New York: McGraw-Hill.
Kumar, V. & Maitra, A. (2004). Diseases of Infancy and Childhood. In Robins and Cotran Pathologic Basis of Disease, Vol I, Seventh Edition (p. 491-495). Philadelphia: Saunders.
Roberts, J.A.F. & Pembrey, M.E. (1985). An Introduction to Medical Genetics. Oxford: Oxford University Press.
Ryan, S. (2006). Cystic Fibrosis. In Washington Manual(R) Pulmonary Medicine Subspecialty Consult, The, 1st Edition (p. 119). Philadelphia: Lippincott Williams & Wilkins.
Welsh, M.J. (2007). Cystic Fibrosis. In Goldman: Cecil Medicine, 23rd Edition (Online print).