Cystic Fibrosis

Cystic fibrosis History Symptomatic diseases Diagnosis and monitoring Treatment Prognosis

History

The name cystic fibrosis comes from the characteristic histologic (microscopic) appearance of the pancreas in the disease, with cysts (fluid filled cavities) and fibrosis prominently seen. Formerly known as "cystic fibrosis of the pancreas," this entity has increasingly been labeled simply "cystic fibrosis."

Although the entire clinical spectrum of CF was not recognized until the 1930s, certain aspects were identified much earlier. Indeed, literature from Germany and Switzerland in the 18th century warned, "Wehe dem Kind, das beim Kuß auf die Stirn salzig schmekt, es ist verhext und muss bald sterben" — "Woe is the child kissed on the forehead who tastes salty, for it is cursed and soon must die," recognizing the association between the salt loss in CF and illness.

In the 19th century, Carl von Rokitansky described a case of fetal death with meconium peritonitis, a complication of meconium ileus associated with cystic fibrosis. Meconium ileus was first described in 1905 by Karl Landsteiner. In 1936, Guido Fanconi published a paper describing a connection between celiac disease, cystic fibrosis of the pancreas, and bronchiectasis.

In 1938 Dorothy Hansine Andersen published an article, "Cystic Fibrosis of the Pancreas and Its Relation to Celiac Disease: a Clinical and Pathological Study," in the American Journal of Diseases of Children. She described the characteristic cystic fibrosis of the pancreas and correlated it with the lung and intestinal disease prominent in CF. She also first hypothesized that CF is a recessive disease and first used pancreatic enzyme replacement to treat affected children. In 1952 Paul di Sant' Agnese discovered abnormalities in sweat electrolytes; a sweat test was developed and improved over the next decade.

In 1988 the first mutation for CF, ?F508 on the seventh chromosome, was discovered by Francis Collins, Lap-Chee Tsui and John R. Riordan. Research has subsequently found over 1,000 different mutations that cause CF. Lap-Chee Tsui led a team of researchers at the Hospital for Sick Children in Toronto that discovered the gene responsible for CF in 1989. Cystic fibrosis represents the first genetic disorder elucidated strictly by the process of reverse genetics.

Because mutations in the CFTR gene are typically small, classical genetics techniques had been unable to accurately pinpoint the mutated gene. Using protein markers, gene-linkage studies were able to map the mutation to chromosome 7. Chromosome-walking and -jumping techniques were then used to identify and sequence the gene.