Neurofibromatosis types 1 and 2 (NF1 and NF2), tuberous sclerosis complex
(TSC1 and TSC2), and von Hipple-Lindau disease (VHL) are neurocutaneous
disorders that are loosely classified as phakomatoses. Neurocutaneous
conditions are also discussed in Chapter 578.
The phakomatoses are generally autosomal dominant conditions
that show a consistent pattern of abnormal growth of various tissues,
and each affected individual has unique and unpredictable manifestations. The
variability of clinical expression of cutaneous manifestations and tumors
distinguishes each of these disorders, and this variability has multiple
causes, including modifier loci, somatic mutation, and simple stoichiometry
in cells with haploinsufficiency of the respective neurocutaneous
gene. Somatic mutation leading to inactivation of the normal neurocutaneous
gene allele, termed second hits or loss of heterozygosity
(LOH), in individuals who have a constitutional mutation is a common
theme and suggests that genes causing neurocutaneous disorders fit
the paradigm of tumor suppressors. Characterization of these genes
has led to the identification of biochemical pathways involved in intracellular
growth signaling pathways; this information led to the development
of novel therapeutic regimens strategically targeted to the regulation
of growth of benign tumors associated with these conditions.
Neurofibromatosis type 1 (NF1) is the most common neurocutaneous
disorder, affecting approximately 1 in 3000 people worldwide. The
hallmark features of NF1, café au lait spots 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 myriad medical
complications which 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 age dependence of clinical manifestations made it essential
to develop a well-accepted set of clinical criteria to establish
the diagnosis (eTable 182.1).1-3 The
typical clinical manifestations allow the diagnosis to be established
in children by 10 years.4 By virtue of full penetrance
in the adult population, diagnosis of NF1 is more straightforward
in familial cases because it requires only one physical manifestation
in addition to an affected first-degree relative. In sporadic cases,
NF1-related associations that are not part of the diagnostic criteria
sometimes appear prior to the development of a second diagnostic
eTable 182.1. Diagnostic
Criteria for Neurofibromatosis 1 (NF1) |Favorite Table|Download (.pdf)
eTable 182.1. Diagnostic
Criteria for Neurofibromatosis 1 (NF1)
|Six or more café au lait macules more than 5 mm
in greatest diameter in prepubertal individuals and more than 15
mm in greatest diameter in postpubertal individuals |
|Two or more neurobromas of any type or one plexiform neurobroma |
|Freckling in the axillary or inguinal regions |
|Optic glioma |
|Two or more Lisch nodules (iris hamartomas) |
|A distinctive osseous lesion such as sphenoid dysplasia or
long bone bowing with or without pseudarthrosis|
|A rst-degree relative (parent, ...|
Log In to View More
If you don't have a subscription, please view our individual subscription options below to find out how you can gain access to this content.
Want remote access to your institution's subscription?
Sign in to your MyAccess profile while you are actively authenticated on this site via your institution (you will be able to verify this by looking at the top right corner of the screen - if you see your institution's name, you are authenticated). Once logged in to your MyAccess profile, you will be able to access your institution's subscription for 90 days from any location. You must be logged in while authenticated at least once every 90 days to maintain this remote access.
If your institution subscribes to this resource, and you don't have a MyAccess profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus.
AccessPediatrics Full Site: One-Year Subscription
Connect to the full suite of AccessPediatrics content and resources including 20+ textbooks such as Rudolph’s Pediatrics and The Pediatric Practice series, high-quality procedural videos, images, and animations, interactive board review, an integrated pediatric drug database, and more.
Pay Per View: Timed Access to all of AccessPediatrics
24 Hour Subscription $34.95
48 Hour Subscription $54.95
Pop-up div Successfully Displayed
This div only appears when the trigger link is hovered over.
Otherwise it is hidden from view.