1. Neurocutaneous Disorders
Neurology Rotation Lecture Series
Last Updated by Lindsay Pagano
Summer 2013

2. Patient Presentation
5 year old male presents for evaluation of macrocephaly and skin lesions
history of seizures, controlled on keppra via PCP
skin lesions noted by PCP, mom says new and not birthmarks
?mild scoliosis
exam: 90th%ile for HC, bilateral axillary freckling, 7 hyperpigmented areas; neuro exam normal
questions? differential?

3. Neurocutaneous Disorders
Neurofibromatosis 1/von Recklinghausen disease
Diagnosis
2 or more of:
6 or more café au lait macules
FHx in 1st degree relative
2 or more neurofibromas OR 1 plexiform neurofib
optic glioma
lisch nodules
osseous lesion
Neuro
seizure
intracranial tumor
nerve sheath, root tumor
polyneuropathy
vasculopathy
macrocephaly
learning disability
UBOs

4. NF1 Cutaneous Ocular optic gliomas lisch nodules Skeletal scoliosis
café au lait macules
Other
Ocular
optic gliomas
lisch nodules
Skeletal
scoliosis
pseudoarthrosis
sphenoid dysplasia
HTN, renovascular
neurofibroma
Cutaneous
axillary freckling
plexiform neurofibromas

5. Neurofibromatosis 2 Cutaneous Neuro Other café au lait macules
intracutaneous tumors
subcutaneous nodules
skin plaques
Neuro
acoustic neuromas
spinal tumors
meningiomas
mononeuropathy
Other
Ocular:
posterior subcapsular lens opacities
retinal hamartoma
epiretinal membrane

6. Tuberous Sclerosis Neuro Diagnosis Other cortical tubers
infantile spasms (50%)
subependymal nodules
ID, DD
giant cell tumors
behavioral concerns
white mater heterotopia
Seizures (90%)
Diagnosis
TSC1, TSC2
Major, Minor criteria
Definite
2 major
1 major + 2 minor
Probable
1 major + 1 minor
Possible
1 major
2 or more minor
Other
Ocular
retinal hamartomas
achromic patches
Cardiac
atrial rhabdo
Renal
angiomyolipomas
Lung
 lymphangioleiomyomatosis (LAM)

7. TS Cutaneous periungual fibroma Shagreen patch hypomelanotic macule
facial angiofibromas

8. Sturge-Weber Syndrome
Neuro
Seizures
focal  generalized tonic clonic
Leptomeningeal angioma
pia mater
IL to port wine stain
MC occipital and parietal areas affected
Hypoperfusion injury
ID, DD
Progressive

9. Sturge-Weber Cutaneous Other Port Wine Stain 10% incidence of SWS
Hemifacial hemangioma
CN5
progressive
Other
Ocular
visual field defects
glaucoma
other vascular anomalies
IL heterochromic iris
GH deficiency
central hypothyroidism

10. PREP Question
You care for a 5 year old girl who recently received a diagnosis of neurofibromatosis type 1. Her parents tell you that they have read that NF1 is associated with an increased risk for cancers, and they ask you for more information.
Of the following, the MOST accurate statement regarding cancers associated with NF1 is that:
Leukemia is an unlikely cancer type
Lisch nodules predispose to tumors of the eye
Optic glioma most commonly presents at the onset of puberty
Pheochromocytoma is common in early childhood
Plexiform neurofibromas may show malignant transformation

11. E. Plexiform neurofibromas may show malignant transformation
NF1- facts we haven’t covered
Cells have only half the normal amount of intracellular neurofibromin
Most tumors are benign, but overall increased risk of malignancy by 5%
Plexiform neurofibromas occur in 25% of NF patients, and undergo malignant transformation to neurofibrosarcoma in 10-15%
Malignant transformation signs include rapid tumor growth and pain
Regarding the other choices:
A. Leukemia: myeloproliferative and myelodysplastic leukemias are associated with NF1
B. Lisch nodules: hamartomas in the iris stroma; benign
C. Optic glioma: 15% patients; before age 6; benign
D. Pheochromocytoma: increased incidence, occurs in adulthood