Neurofibromatosis

Question 1

Incidence rate of neurofibromatosis type 1

Answer 1

1 in 3000 births

Question 2

What are the 3 types of neurofibromatosis

Answer 2

NF1, NF2, and schwannomatosis

All are characterized by development of nerve sheath tumors

Question 3

Who establishes the criteria for diagnosing NF?

Answer 3

National Institute of Health (NIH)

Question 4

What is the NIH criteria for diagnosing NF1

Answer 4

Two or more of the following (diagnosis may be unresolved for years):

1. At least 6 cafe-au-lait máculas (>5 mm in diameter for prepubertal individuals and > 15 mm in post-pubertal individuals
2. Freckling in auxiliary or inguinal regions
3. Optic glioma
4. At least 2 Lish nodules (Iris hamartomas)
5. At least 2 neurofibromas of any type or one plexiform neurofibroma
6. A distinctive osseous lesion (sphenoid dysplasia or tibial dysplasia)
7. A first degree relative with NF1

Question 5

What is a neurocutaneous disorder

Answer 5

Shows prominent manifestations on the skin and in the nervous system

Question 6

Most common types of neurocutaneous disorders

Answer 6

Neurofibromatosis, tuberous sclerosis complex, and sturge weber syndrome

Question 7

What is the most common type of Neurofibromatosis

Answer 7

NF1

Question 8

What is the progression of cafe-au-lait spots

Answer 8

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

Question 9

When does skin fold freckling occur

Answer 9

Between ages 3-5 years

Question 10

What are neurofibromas

Answer 10

Benign tumors of the nerve sheath that arise from Schwann cells

Question 11

What is the course of neurofibromas

Answer 11

Dermal ones typically seen in adults and can be disfiguring

Often not seen in pre-pubertal children

Question 12

Incidence of brain tumors in people with NF1

Answer 12

15% and the majority are benign optic gliomas - most occur before 6 years old

Question 13

What are plexiform neurofibromas

Answer 13

Arise from Schwann cells and are focal growths that grow longitudinally

Question 14

What characterizes NF2

Answer 14

Bilateral acoustic schwannomas on the eighth cranial nerve, meningiomas, and ependymomas. Also affects the spinal cord

Question 15

What characterizes schwannomatosis?

Answer 15

Associated with schwannomas and chronic pain

Question 16

Genetic properties of NF1

Answer 16

An autosomal dominant genetic disorder

Genetic gene mutations in 95% of individuals who fulfill criteria - most often loss of function of NF1 gene product

Question 17

Percentage of individuals with NF1 that have a plexiform neurofibroma

Answer 17

50%

Question 18

What is the course of growth for plexiform neurofibromas

Answer 18

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

Question 19

Course and characteristics of optic glioma

Answer 19

Typically form between ages 2-6 years old

Most often asymptomatic but can cause visual loss or hypothalamic disturbance if the chiasm is involved

Question 20

Neuropsychological findings in NF1

Answer 20

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

Question 21

Mortality in individuals with NF1

Answer 21

50-60 years old but individuals with mild symptoms can have average life expectancy

Question 22

Neuropathology in NF1

Answer 22

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

Question 23

What are UBOs

Answer 23

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

Question 24

Genetic cause for NF1

Answer 24

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

Question 25

Psychological findings with NF1

Answer 25

Increased internalizing problems vs. externalizing problems
(Anxiety and depression)

More social deficits