Single Gene Disorders: Neurofibromatosis

The transmission of single genes in humans is called Mendelian or single gene inheritance. Compared to infectious diseases or multifactorial conditions such as cancer, single gene disorders are relatively rare. Single gene disorders generally affect 1 in 10,000 or fewer individuals. The term ‘mode of inheritance’ refers to the patterns that inherited traits follow within a family. Dominant and recessive are two modes of inheritance that resulted from the studies and laws of Gregor Mendel. Knowing the modes of inheritance allows genetic counselors to calculate the probability of inheritance of a particular disorder.

An example of a dominant disorder in humans is Neurofibromatosis. Descriptions of Neurofibromatosis or NF first appeared in the 18th century, but the disorder was more fully characterized in 1882 by a German pathologist, Friedrich von Recklinghausen. NF is a neurocutaneous disorder characterized by tumorous growths (neurofibromas) which affect the nervous system and skin. There are two main types of NF: NF1 and NF2. NF1 is the more common with an incidence of 1 in 3000 individuals.

Physical expression of the mutation is extremely variable, meaning that affected members in the same family may show striking differences in severity, even though they have the same condition. Approximately one-half of NF1 patients have a positive family history and one-half are due to new mutations. Each child of a parent with NF has a 50% chance of inheriting the same condition.

The NF1 gene is on chromosome 17 and was identified and mapped in 1987. The gene codes for a protein called neurofibromin which functions as a tumor suppressor. Clinical features include small pigmented areas on the skin called café-au-lait spots (CALS), axillary freckling, pigmented areas on the iris called Lisch nodules, and neurofibromas. Learning disabilities, developmental delays and cardiovascular complications are frequently seen with NF.

NF is worldwide in its distribution, having no particular racial, geographic, or ethnic preference. It affects both males and females equally. Currently there is no cure for this condition but direct genetic testing is now available.

For more information on NF you can visit the web site for the National NF Foundation at www.nf.org.