Phakomatoses, also known neurocutaneous syndromes, are a group of multisystemic diseases that most prominently affect structures primarily derived from the ectoderm such as the central nervous system, skin and eyes. The majority of phakomatoses are single-gene disorders that may be inherited in an autosomal dominant, autosomal recessive or X-linked pattern. Presentations may vary dramatically between patients with the same particular syndrome due to mosaicism, variable expressivity, and penetrance.Many phakomatoses are caused by mutations which alter functioning of the RAS–mitogen-activated protein kinase (MAPK) pathway that regulates cellular growth, differentiation, proliferation and death. This results in a tendency for individuals with these mutations to develop various types of benign or malignant tumors depending on the particular mutation. The presence of these tumors may result in functional and/or cosmetic problems depending on their type and location. History
The term phakomatosis originated in 1923, when the Dutch ophthalmologist van der Hoeve used the term phakoma to refer to a "mother spot" or birthmark, a physical characteristic common to patients with tuberous sclerosis and neurofibromatosis that he examined. The term phakomatoses was derived from phakos, the Greek term for birthmark. He originally used the phrase to describe two diseases: neurofibromatosis and tuberous sclerosis. This term later became imprecise when van der Hoeve also used it to include those with Sturge-Weber syndrome as they do not have similar lesions on the skin. In addition, the term phakomatosis makes no reference to the central nervous system involvement.
The term neurocutaneous syndrome was subsequently defined by the Russian-American neurologist Paul Ivan Yakovlev and psychiatrist Riley H. Guthrie and it is currently more commonly used.The first clinical description was made in “Monstrorum Historia” by an Italian physician and naturalist named Ulisse Aldrovandi who described a patient with probable neurofibromatosis type I in 1592. He described a short man with a large tumor which was likely a plexiform neurofibroma. However, there are artistic or descriptive representations which have been speculated to depict individuals with phakomatoses as far back as the Hellenistic period and ancient Egypt.Over time, the number of neurocutaneous syndromes have increased and there are several dozen that have been characterized. Types
There are a large number of neurocutaneous syndromes that exceed the scope of this article. Therefore, characteristics of a few of the more common types are summarized. Neurofibromatosis Type I (von Recklinghausen disease)
Neurofibromatosis type 1 is the most common phakomatosis and it affects approximately 1 in 2500-3000 live births. It is a genetic disorder due to a germline mutation in the NF1 gene. This gene encodes a protein called neurofibromin that is involved in controlling cellular growth. Malfunction of the gene results in multisystem manifestations involving the skin, central nervous system, peripheral nervous system, eyes and musculoskeletal system. The condition is inherited in an autosomal dominant manner. However, approximately one-half of patients with this condition have no family history and the mutation occurs spontaneously.