Neurofibromatosis (commonly abbreviated NF) is a genetically-inherited disorder in which the nerve tissue grows tumors (i.e., neurofibromas) that may be harmless or may cause serious damage by compressing nerves and other tissues. The disorder affects all neural crest cells (Schwann cells, melanocytes, endoneurial fibroblasts). Cellular elements from these cell types proliferate excessively throughout the body forming tumors and the melanocytes function abnormally resulting in disordered skin pigmentation.The tumors may cause bumps under the skin, colored spots, skeletal problems, pressure on spinal nerve roots, and other neurological problems.[1]
Neurofibromatosis is autosomal dominant, which means that it affects males and females equally and is dominant (only one copy of the affected gene is needed to get the disorder). Therefore, if only one parent has neurofibromatosis, his or her children have a 50% chance of developing the condition as well. The severity in affected individuals, however, can vary (this is called variable expressivity). Moreover, in around half of cases there is no other affected family member because a new mutation has occurred.

Neurofibromatosis type 1

Neurofibromatosis type 1 - mutation of neurofibromin chromosome 17q11.2. The diagnosis of NF1 is made if any two of the following seven criteria are met:
  • Two or more neurofibromas on the skin or under the skin or one plexiform neurofibroma (a large cluster of tumors involving multiple nerves); Neurofibromas are the subcutaneous lumps that are characteristic of the disease and increase in number with age.
  • Freckling of the groin or the axilla (arm pit).
  • Café au lait spots (pigmented, most often a shade of brown, smooth edges(coast of california)[2] birthmarks). Six or more measuring 5 mm in greatest diameter in prepubertal individuals and over 15 mm in greatest diameter in postpubertal individuals
  • Skeletal abnormalities, such as sphenoid dysplasia or thinning of the cortex of the long bones of the body (i.e. bones of the leg, potentially resulting in bowing of the legs)
  • Lisch nodules (hamartomas of iris), freckling in the iris.
  • Tumors on the optic nerve, also known as an optic glioma
  • A first-degree relative with a diagnosis of NF1

Neurofibromatosis type 2

Neurofibromatosis type 2 - mutation of NF2 (Merlin) in chromosome 22q12


Schwannomatosis - gene involved has yet to be identified
  1. Multiple Schwannomas occur.
  2. The Schwannomas develop on cranial, spinal and peripheral nerves.
  3. Chronic pain, and sometimes numbness, tingling and weakness.
  4. About 1/3 of patients have segmental Schwannomatosis, which means that the Schwannomas are limited to a single part of the body, such as an arm, a leg or the spine.
  5. Unlike the other forms of NF, the Schwannomas do not develop on vestibular nerves, and as a result, no loss of hearing is associated with Schwannomatosis.
  6. Patients with Schwannomatosis do not have learning disabilities related to the disease.
One must keep in mind, however, that neurofibromatosis can't occur in or affect any of the organ systems, whether that entails simply compressing them (from tumor growth) or in fact altering the organs in some fundamental way. This disparity in the disease is one of many factors that makes it difficult to diagnose, and eventually find a prognosis for.

Genetics and Hereditability

Neurofibromatosis type 1 is due to mutation on chromosome 17q11.2 , the gene product being Neurofibromin ( a GTPase activating enzyme).[3]

Neurofibromatosis type 2 is due to mutation on chromosome 22q , the gene product is Merlin, a cytoskeletal protein. Both NF1 and NF2 are autosomal dominant disorders, meaning that only one copy of the mutated gene need be inherited to pass the disorder. A child of a parent with NF1 or NF2 and an unaffected parent will have a 50%-100% chance of inheriting the disorder, depending on whether the affected parent is heterozygous or homozygous for the trait.
Complicating the question of heritability is the distinction between genotype and phenotype, that is, between the genetics and the actual manifestation of the disorder. In the case of NF1, no clear links between genotype and phenotype have been found, and the severity and specific nature of the symptoms may vary widely among family members with the disorder.[4] In the case of NF2, however, manifestations are similar among family members; a strong genotype-phenotype correlation is believed to exist (ibid).
Both NF1 and NF2 can also appear to be spontaneous mutation, with no family history. These cases account for about one half of neurofibromatosis cases (ibid).
Similar to polydactyly, although NF is a dominant mutation, it is not prevalent in society. Neurofibromatosis-1 is found in approximately 1 in 2,500-3,000 live births (carrier incidence 0.0004, gene frequency 0.0002). NF-2 is less common, having one case in 50,000-120,000 live births.[5]