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.
Whereas other syndromes such as Noonan syndrome with multiple lentigines, for instance, do not. In cases where conditions that do not have diagnostic criteria are suspected, genetic testing is more likely to be necessary. Diagnostic criteria are not perfect as sensitivity and specificity is not 100%. Similarly, genetic testing can produce false negatives. For example, genetic testing is positive in only 75-90% of cases of tuberous sclerosis complex. Thus, clinicians must apply clinical judgement when evaluating an individual suspected to have a neurocutaneous syndrome. Treatment
The treatment of each neurocutaneous syndrome is unique. For some neurocutaneous syndromes such as neurofibromatosis 1 and tuberous sclerosis complex there are guidelines with recommendations for surveillance and management. For less common syndromes such guidelines are not yet available. Surveillance is a necessity for many neurocutaneous syndromes because new manifestations may develop over time which may only be detected with specific and focused testing. Thus, patients may be advised to obtain particular evaluations (e.g., MRI, ophthalmologic or dermatological examinations) within recommended intervals over time with the aim of detecting new manifestations of the syndrome early on. Most of the currently available treatments for neurocutaneous syndromes do not address the underlying genetic cause. For example, epilepsy surgery in tuberous sclerosis complex or vestibular schwannoma surgery in neurofibromatosis type 2. However, there are some treatments that do address the underlying cause such as the use of mTOR inhibitors in tuberous sclerosis complex.