Neurofibromatosis

Inheritance	autosomal dominant
Occurrence	1 in 4,000
Description	trait characterized by cafe-au-lait ("coffee and milk" pigmented skin) spots and small tumor-like growths on or under the skin-- deformation of bones and curvature of the spine can also be symptoms
Location of gene	Chromosome 17
New cases	Nearly half of all neurofibromatosis cases are not inherited but the result of new mutations in the gene. This is most likely the case due to the large size of the gene. The gene is over 350 kb; the mRNA is 11-13 kb with 59 exons

This condition provides an excellent example of how modern genetics and technology can help clarify and bring understanding to common diseases. Additionally, it brings together history, drama, science, and technology. It would be profitable to combine this work with an English teacher and have the students read "The Elephant Man."

Joseph Merrick was a severely disfigured man who lived in Great Britain during the late 1800's. He was exhibited in "freak shows" and carnivals throughout the country. He was the first touring sideshow. People were morbidly fascinated by his grotesque appearance. Many drawings attempt to depict Merrick-- he had an enormous right arm and had fibrous growths all over his skin and body. After his death, he was said to have Neurofibromatosis. That one widely publicized "fact" has caused much fear and apprehension about Neurofibromatosis (NF), a very common genetic trait that is most commonly only cafe-au-lait spots on the skin.

In 1986 two researchers suggested that perhaps Merrick did not suffer from NF after all. Although he had fibrous tumors he lacked the diagnostic cafe-au-lait spots, and he had no family history of the disorder. The researchers argued that the disorders Merrick suffered from were "much more bizarre" than those commonly associated with neurofibromatosis. He actually suffered (most probably) from Proteus Syndrome. (Tibbles, J. A. R. and Cohen, M. M. 1986. Medical History Section of the British Medical Journal.) When individuals were first diagnosed with NF, they feared their condition and feared developing into a "freak show." Although many individuals do develop fibrous tumors, it is a rare individual who has very severe symptoms. The possibility that Merrick did not have NF has helped remove much of the stigma associated with NF.

As a class, discuss what forms of technology could have aided these researchers when they tried to determine whether Joseph Merrick really had NF-- gene mapping, sequencing, restriction enzyme digests, and/or electrophoresis

A more advanced class could research for themselves what Joseph Merrick most likely had. Have them plan what technology to use and know what each could accomplish. Some students may conclude Merrick suffered from Neurofibromatosis. Point out that (1) Merrick did not have a family history of NF, but that the size of the gene does allow for fresh mutations quite commonly and (2) Merrick did not have any of the characteristic cafe-au-lait spots.

Discuss how some people could feel finding out they had NF and wrongly assuming that it is the same disease the Elephant Man suffered from. How has this correction helped people who have NF?