Neurocutaneous disorders are a heterogeneous group of genetic conditions affecting both the central and peripheral nerves that can result in brain, spine, skin, and skeletal manifestations. This chapter discusses select neurocutaneous disorders, or phakomatoses, in which seizures are not a typical component. Neurocutaneous disorders with prominent neurologic features, particularly seizures, are discussed separately (see Chapter 567). A comprehensive table of neurocutaneous disorders (Table 176-1) and selected more commonly observed conditions are described below.
TABLE 176-1NEUROCUTANEOUS DISORDERS ||Download (.pdf) TABLE 176-1NEUROCUTANEOUS DISORDERS
|Encephalocraniocutaneous lipomatosis |
|Epidermal nevus syndrome (linear sebaceous nevus, linear epidermal nevus) |
|Nevoid basal cell carcinoma syndrome (Gorlin syndrome) |
|Hypomelanosis of Ito |
|Incontinentia pigmenti |
|Neurocutaneous melanosis |
|Neurofibromatosis type 1 |
|Neurofibromatosis type 2 |
|Sturge-Weber syndrome |
|Tuberous sclerosis complex |
|Von Hippel-Lindau disease |
Neurofibromatosis type 1 (NF1, Online Mendelian Inheritance in Man [OMIM] no. 162200) is the most common neurocutaneous disorder, and one of the most common autosomal dominant disorders affecting approximately 1 in 3000 people worldwide. The hallmark features of NF1, café-au-lait macules and benign cutaneous neurofibromas, typically arise in early childhood and adolescence, respectively. Approximately two-thirds of individuals with NF1 have manifestations that generally do not require clinical intervention, whereas the remaining one-third display a myriad of medical complications that are unpredictable, both in timing and severity.
Even though NF1 has been recognized as von Recklinghausen disease by the medical community since the 19th century, both its variability and the age-dependent penetrance of its clinical manifestations made it essential to develop a well-accepted set of clinical criteria to establish the diagnosis (Table 176-2). The typical clinical manifestations allow the diagnosis to be established in children by 8 years according to a set of clinical criteria known as the National Institutes of Health (NIH) consensus criteria for NF1. By virtue of full penetrance in the adult population, diagnosis of NF1 is more straightforward in familial cases because it requires only 1 physical manifestation in addition to an affected first-degree relative. In sporadic cases, features associated with NF1 that are not part of the diagnostic criteria sometimes appear prior to the development of a second diagnostic sign, for example, characteristic T2 hyperintensities on brain magnetic resonance imaging (MRI).
TABLE 176-2NATIONAL INSTITUTES OF HEALTH CONSENSUS DIAGNOSTIC CRITERIA FOR NEUROFIBROMATOSIS 1 (NF1) ||Download (.pdf) TABLE 176-2NATIONAL INSTITUTES OF HEALTH CONSENSUS DIAGNOSTIC CRITERIA FOR NEUROFIBROMATOSIS 1 (NF1)
|6 or more café-au-lait spots > 5 mm in greatest diameter in prepubertal individuals or > 15 mm in greatest diameter in postpubertal individuals |
|2 or more neurofibromas of any type or 1 plexiform neurofibroma |
|Axillary or inguinal freckling |
|Optic pathway glioma |
|2 or more Lisch nodules (iris hamartomas) |
|A distinctive osseous lesion such as sphenoid dysplasia or tibial pseudoarthrosis...|