Neuro 50: Phakomatoses

Question 1

Phakomatoses: what are they? & what are their 4 common manifestations?

Answer 1

• neurocutaneous syndromes
• common manifestations:
  1. lesions of the skin or mucous membranes
  2. CNS abnormalities
  3. variety of opthalmologic, visceral and endocrine disorders -usually neoplastic
  4. genetic transmission - often autosomal dominant
• other than these 4 things, they have little in common

Question 2

Name 4 phakomatoses

Answer 2

1. neurofibromatosis type 1 = “von recklinghausen’s disease”
2. neurofibromatosis type 2 = “central neurofibromatosis”
3. Tuberous Sclerosis = bouneville’s disease
4. von hippel-lindau disease = retino-cerebral angiomatosis
5. sturge-weber disease = encephalo-facial angiomatosis (sporadic)

Question 3

Neurofibromatosis type 1: epidemiology & genetics

Answer 3

• AKA NF-1 or Von Recklinghausen’s disease
• most common phakomatoses
• autosomal dominant, but 1/3 of cases are new mutations
• abnormal neurofibromin protein coded for on chromosome 17

Question 4

NF-1’s neurofibromas

Answer 4

• can be “ordinary” neurofibromas, schwannomas, or plexiform neurofibroma
• PERIPHERAL nerve sheath tumor
• nerve sheath tumor –> contain all of the “ingredients” of the peripheral nerves, but just enlarged and distorted
• push and displace the normal nerve fibers
• also found in the viscera in a wide distribution –> can be found in any place where peripheral nerves are found in the body

Question 5

Plexiform neurofibroma

Answer 5

• pahtognomonic neurofibromas of NF-1
• prone to progress to malignancy
• feels like a “bag of worms” under the skin
• histologically will see a wavy pattern of the nerve fibers

Question 6

Cafe-au-lait spots

Answer 6

• brown macular lesions
• pigmentation is caused by the macromelanosomes
• usually found on the trunk
• increase in number and size w/ age
• see in NF-1 pts (usually >6 spots) and even in “uneffected” family members
• less commonly seen in NF-2

Question 7

Lisch nodules

Answer 7

• pigmented nodules in the iris
• can be found in pts with NF-1
• progress w/ age

Question 8

Optic nerve glioma

Answer 8

• most common brain tumor in the 1st decade of life
• if the pt has bilateral optic gliomas then they have NF-1!! –> pathogneumonic!
• may be asympromatic
• if the visual acuity is ok and there is no increased ICP, then just follow w/out tx
• can be seen in NF-1

Question 9

3 other clinical manifestations of NF-1?

Answer 9

1. Central tumors - optic nerve glioma, brainstem glioma, astricytoma, meningionma, ependymoma
2. spinal cord lesions - tumors, neurofibromas in the spinal cord, syringomyelia
3. hydrocephalus - aqueductal stenosis or tumors

Question 10

Removal of schwannoma v. neurofibroma?

Answer 10

• schanommas are more easily dissected away and removed

- neurofibrotomas are very hard to remove w/out sacrificing the nerve

Question 11

NF-2: epidemiology and genetics

Answer 11

• AKA “central” neurofibromatosis or BILATERAL ACOUSTIC SCHWANNOMAS
• less common than NF-1
• merlin is the defective protein, on chromosome 22 –> normal protein probably regulates membrane receptor signalling & contact growth inhibition
• autosomal dominant

Question 12

Common locations of lesions in NF-2?

Answer 12

• primarily seen in the cranial cavity and the vertebral canal: bilateral acoustic schwannomas, meningiomas (usu. multiple), gliomas, epndymomas, schwann cell tumors in the sc, glial heterotopias, syringomyelia
• *bilateral acoustic schannomas is usually considered pathogneumonic!

Question 13

Bilateral acoustic schwannoma

Answer 13

• pathognuemonic for NF-2

- slow growing –> can be asymptomatic!

Question 14

Glial Hamartomas

Answer 14

• see tissue type that is supposed to be in that location, but it has just abnormally proliferated
• haphazard arrangements of funny looking cells (mostly astrocytes)
• can cause seizures
• seen in Tuberous sclerosis

Question 15

Tuberous sclerosis: genetics

Answer 15

• usually 2 loci:
  1. hamartin on chrom 9
  2. tuberin on chrom 16
• autosomal dominant –> but new mutations account for half of the cases!

Question 16

Tuberous sclerosis: triad of sx

Answer 16

1. seizures
2. mental retardation
3. skin lesions = “adenoma sebaceum” or others

Question 17

Adenoma sebaceum

Answer 17

• nodular reddish brown rash seen on the face esp in the nasolabial folds
• most common face lesion seen in tuberous sclerosis
• found in the distribution of the sebaceous glands of the face

Question 18

Depigmented nevi

Answer 18

• other skin lesion that can be seen in tuberous sclerosis

- can be the earliest sign of the disease –> can be seen in infants!

Question 19

Subungual fibromas

Answer 19

• another skin lesion that can be seen in tuberous sclerosis
• actually angiofibromas
• found near nails on fingers and toes

Question 20

Shagreen patches

Answer 20

• another skin lesion that can be seen intuberous sclerosis

- irregularly shaped raised pale patches with the feel of untanned leather

Question 21

Cortical tuber

Answer 21

• “classic tuber” CNS lesion of Tuberous sclerosis
• looks like an enlarged gyrus on the cortical surface
• has a smooth surface
• microscopically it shows a loss of normal lamination & has lg bizarre cels that contain both neural and glial markers
• these are the cause of the seizures and the mental retardation

Question 22

Subependymal nodules

Answer 22

• another CNS lesion that can be seen in tuberous sclerosis
• similar histologically to the classic tubers
• look like small bumps on the ventricular system
• often called “candle gutterings” b/c resemble solidified drops of wax that drip from a candle

Question 23

Subependymal giant cell astrocytoma

Answer 23

• another CNS lesion that can be seen in tuberous sclerosis
• tumor-like proliferation of the same bizzare cells seen in the tubers and subependymal nodules
• not malignant
• can obstruct CSF flow –> cause hydrocephalus
• can cause death via increased ICP!

Question 24

Visceral manifestations of tuberous sclerosis?

Answer 24

• variable and can include a variety of hamartomaous lesions
• can be in various locations –> lungs, kidneys, GI tract, etc.
• most common is cardiac rhabdomyomas –> can cause death by mechanically interfering w/ cardiac contraction

Question 25

Von Hippel-lindau diasease: genetics

Answer 25

• autosomal dominant w/ high penetrance

- on chromosome 3

Question 26

Von-hippel-lindau disease:3 clinical findings

Answer 26

1. hemangioblastomas - of retina, cerebellum, spinal cord
2. renal cell carcinoma
3. Cysts - in kidneys, pancreas, liver

Question 27

Sturge-weber syndrome: genetics

Answer 27

-NOT inherited!

Question 28

Sturge-weber syndrome: skin

Answer 28

• see port wine stains that usually are in the distribution of the opthalmic division of CN V, but can be in the buccal mucose, tounge, palate, or pharynx
• usually unilateral
• present at birth

Question 29

Dilantin

Answer 29

• seizure medication

- if given in high doese it can cause hyperplasia of the gingiva!

Question 30

Sturge-weber syndrome: CNS

Answer 30

-can have a venous angioma in the pia matter that is ipsilateral to the port wine stain –> most commonly in the occipital region, but can be in the temporal or parietal –> the cortex under the angioma will have neuronal loss, gliosis & calcification

Question 31

Sturge-weber syndrome: 5 common clinical sx

Answer 31

1. seizures - with infant onset usually
2. homonymous heminanopia - usually contralateral to portwine stain
3. hemiplegia - usually contralateral to portwine stain
4. mental retardation
5. glaucoma