Neurofibromatosis Flashcards
Incidence rate of neurofibromatosis type 1
1 in 3000 births
What are the 3 types of neurofibromatosis
NF1, NF2, and schwannomatosis
All are characterized by development of nerve sheath tumors
Who establishes the criteria for diagnosing NF?
National Institute of Health (NIH)
What is the NIH criteria for diagnosing NF1
Two or more of the following (diagnosis may be unresolved for years):
- At least 6 cafe-au-lait máculas (>5 mm in diameter for prepubertal individuals and > 15 mm in post-pubertal individuals
- Freckling in auxiliary or inguinal regions
- Optic glioma
- At least 2 Lish nodules (Iris hamartomas)
- At least 2 neurofibromas of any type or one plexiform neurofibroma
- A distinctive osseous lesion (sphenoid dysplasia or tibial dysplasia)
- A first degree relative with NF1
What is a neurocutaneous disorder
Shows prominent manifestations on the skin and in the nervous system
Most common types of neurocutaneous disorders
Neurofibromatosis, tuberous sclerosis complex, and sturge weber syndrome
What is the most common type of Neurofibromatosis
NF1
What is the progression of cafe-au-lait spots
May appear at birth but often gradually appear in the first few postnatal months
Require 6 or more (1-3 máculas are common)
Must be 5 mm before puberty or 15 mm after
When does skin fold freckling occur
Between ages 3-5 years
What are neurofibromas
Benign tumors of the nerve sheath that arise from Schwann cells
What is the course of neurofibromas
Dermal ones typically seen in adults and can be disfiguring
Often not seen in pre-pubertal children
Incidence of brain tumors in people with NF1
15% and the majority are benign optic gliomas - most occur before 6 years old
What are plexiform neurofibromas
Arise from Schwann cells and are focal growths that grow longitudinally
What characterizes NF2
Bilateral acoustic schwannomas on the eighth cranial nerve, meningiomas, and ependymomas. Also affects the spinal cord
What characterizes schwannomatosis?
Associated with schwannomas and chronic pain
Genetic properties of NF1
An autosomal dominant genetic disorder
Genetic gene mutations in 95% of individuals who fulfill criteria - most often loss of function of NF1 gene product
Percentage of individuals with NF1 that have a plexiform neurofibroma
50%
What is the course of growth for plexiform neurofibromas
Can be on the surface or internal and impinge on surround structure
Growth is most rapid during childhood - can grow to cause major disfigurement and hyper trophy of the skin and soft tissues
Typical sites are the eyes, neck, and limbs l
Course and characteristics of optic glioma
Typically form between ages 2-6 years old
Most often asymptomatic but can cause visual loss or hypothalamic disturbance if the chiasm is involved
Neuropsychological findings in NF1
Neurocognitive dysfunction in at least 50%
Often have learning disability in 30-65%
ADHD in 30-50% (equal in girls and boys)
ID in 4-8%
Leftward shift in IQ is seen - average IQ is 89-98
Also see immaturity, poor speech articulation, lack of coordination, and hypotonia
Deficits in attention, executive function, visuospatial weakness (although inconsistent in more recent studies)
Word-list generation, naming, reading comprehension, written expression, and dexterity - prominent nonverbal deficits
Mortality in individuals with NF1
50-60 years old but individuals with mild symptoms can have average life expectancy
Neuropathology in NF1
T2 hyperintensities - focal areas of hyperintensities are seen on T2 weighted MRIs in 60-70% of children with NF1
Called unidentified bright objects
Macroceplay/megalencephaly in 30-50% of people
What are UBOs
T2 hyperintensities (seen in 60-70%)
frequently occur in the basal ganglia, cerebellum, thalamus, brainstem, and subcortical white matter
Suspected to be neural dysplasia or dysmyelination
Usually seen in younger children but decrease or disappear by early adulthood
Genetic cause for NF1
Mutations in the NF1 gene which codes for neurofibromin on chromosome 17 result in inactive neurofibromin causing excessive RAS activity and unregulated growth
Neurofibromin is the down-regulator of RAS - tumor suppressant (ensures cells are not growing or dividing too rapidly or uncontrolled)
RAS is a protein involved in cellular growth and differentiation
