21 - 135 - NEUROFIBROMATOSES

Question 1

Softer than the surrounding connective tissue and protrude just above the skin surface or lie just under the skin with an overlying violaceous hue.

Answer 1

Cutaneous neurofibromas

Question 2

■ Arise from peripheral nerves, both under the skin and deep in the viscera.

■ Generally much harder.

Answer 2

Subcutaneous neurofibromas

Question 3

■ Generally present at birth or apparent during the first several years of life.

■ May lead to disfigurement, blindness (secondary to amblyopia, glaucoma, or proptosis), loss of limb function, or organ dysfunction by compression of vital structures.

Answer 3

Plexiform neurofibromas

Question 4

■ Manifestations of NF-1, usually limited to one area of the body.

■ Occurs as result of a postconceptional mutation in the NF1 gene, leading to somatic mosaicism.

Answer 4

Mosaic neurofibromatosis Type 1 (segmental NF-1)

Question 5

Diagnostic Criteria for Neurofibromatosis Type 1

Answer 5

Question 6

Diagnostic Criteria for Neurofibromatosis Type 1

Answer 6

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Question 9

protrude just above the skin surface or lie just under the skin with an overlying violaceous hue

Answer 9

Cutaneous neurofibromas

They are softer than the surrounding connective tissue, often creating a “buttonholing” sensation when a finger is rubbed gently over the surface

Question 10

Question 11

e benign peripheral nerve sheath tumors that involve single or multiple nerve fascicles, often arising from branches of major nerves.

Answer 11

Plexiform neurofibromas

They may elicit a “wormy” sensation on palpation, as a person feels multiple thickened nerve fascicles.

Often there is overlying hyperpigmentation (“giant café-au-lait spot”) or hypertrichosis (Fig. 135-6).

Question 12

arise from peripheral nerves, both under the skin and deep in the viscera, are generally much harder

Answer 12

Subcutaneous neurofibromas

If they arise from the dorsal root ganglia, they may grow through neural foramina, compressing the spinal cord, creating a “dumbbell” appearance.

Subcutaneous neurofibromas in the neck may feel like a “beaded necklace,” often being confused with lymph nodes.

Question 13

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Question 18

Diagnostic Criteria for Neurofibromatosis Type 2

Answer 18

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Question 21

Question 22

These are often the first manifestation of NF-1 to appear.

Answer 22

Café-au-lait spots, which are flat, pigmented macules

Question 23

Café-au-lait spots smaller than 5 mm are referred as

Answer 23

freckles

commonly present in the axillae, inguinal region, and under the breasts

Question 24

freckles seen in NF1 are commonly present in what locations

Answer 24

commonly present in the axillae, inguinal region, and under the breasts

Question 25

What do you call the presence of axillary (armpit) freckling in people with neurofibromatosis type I (von Recklinghausen's disease)?

Answer 25

**Crowe sign** lesions are not related to sun exposure, and are considered virtually **pathognomonic of NF-1**

Question 26

period of greatest risk for the development of symptomatic optic pathway tumors in NF-1 is during the first how many years of life?

Answer 26

**first 6 years of life**

Question 27

2 bony lesions distinctive enough to be included in the diagnostic criteria for NF-1.

Answer 27

1. **_dysplasia of the wing of the sphenoid bone_,** results in poor formation of the wall and/or floor of the orbit. This congenital mesodermal dysplasia may be, but is not always, clinically apparent, leading to proptosis (from herniation of meninges or brain into the orbit) or enophthalmos. 1. **_Dysplasia of a long bone_,** characterized by congenital thinning and bowing, affects approximately 2% of children with NF-1

Question 28

most common long bone affected in NF1

Answer 28

**_tibia_** femur, humerus and other long bones also may be involved ## Footnote * Even when the bone is intact, thinning and bowing produce a visible deformity, and the weakened mechanical properties of the bone predispose to fracture, particularly in the weightbearing bones. * Failure of primary union following a fracture results in a “false joint,” or pseudarthrosis.

Question 29

Hallmark of NF-2

Answer 29

**presence of bilateral vestibular schwannomas**

Question 30

characteristic cutaneous lesion of NF-2 is

Answer 30

**_cutaneous schwannoma_**

Question 31

More than 50% of children with Noonan syndrome have cardiovascular disease, most commonly \_\_\_\_\_\_\_\_\_

Answer 31

**pulmonary valve stenosis**

Question 32

autosomal dominant transmission of café-au-lait spots, intertriginous freckling, and macrocephaly without any other manifestations of NF-1, including neurofibromas, in whom no NF1 mutation was detected

Answer 32

LEGIUS SYNDROME

Question 33

develop multiple schwannomas but who fail to develop other manifestations of NF-2, particularly vestibular schwannomas

Answer 33

**SCHWANNOMATOSIS**

Question 34

Current diagnostic criteria for a definite diagnosis of schwannomatosis in individuals 30 years of age or older include:

Answer 34

(a) 2 or more nonintradermal schwannomas, at least 1 with histologic confirmation, and (b) diagnostic criteria for NF-2 not fulfilled, and (c) no evidence of vestibular schwannoma on MRI, and (d) no first-degree relative with NF-2, and (e) no germline NF2 mutation.

Question 35

most common skeletal manifestation of NF-1, affecting 10% to 30% of patients

Answer 35

**Scoliosis**

Question 36

The most commonly identified vascular lesion in patients with NF-1 is in what artery?

Answer 36

**_renal artery_**, leading to renovascular hypertension

Question 37

NF-1 is located in which gene locus? ## Footnote a. Long arm of chromosome 17 which encodes for neurofibromin b. Short arm of chromosome 17 which encodes for neurofibromin c. chromosome band 9q34 d. chromosome band 16p13.3 e. chromosome 22

Answer 37

A ## Footnote Answer: A. NF1 is located on the long arm of chromosome 17 p. 2470 C. TSC1 gene maps to chromosome band 9q34 (p. 2485) D. TSC2 gene maps to chromosome band 16p13.3

Question 38

NF-2 is located in which gene locus? a. Long arm of chromosome 17 which encodes for neurofibromin b. Short arm of chromosome 17 which encodes for neurofibromin c. chromosome band 9q34 d. chromosome band 16p13.3 e. chromosome 22

Answer 38

e. chromosome 22 Answer: E. NF2 is caused by mutations in a gene on chromosome 22 which encodes the membrane related protein merlin p.2472

Question 39

Which of the following is included in the diagnostic criteria for NF1 a. 2 or more schwannomas of any type or 1 plexiform neurofibroma b. Six or more café-au-lait macules larger than 15 mmm in greatest diameter in prepubertal individuals, and larger than 5 mm in greatest diameter in postpubertal individuals c. Two or more lisch nodules d. Distinct osseous lesion such as fused, bifid, or markedly splayed ribs

Answer 39

Answer: C. table 135-1 p. 2466

Question 40

A 9-year-old consulted in the OPD with multiple, well-defined, round hyperpigmented macules 5mm in greatest diameter, with axillary freckling and numerous soft nodular masses on the trunk and extremities. There were also similar lesions with the mother. Based on your diagnosis, you will advise the patient the following except? a. Yearly ophthalmologic examinations to look for signs of optic pathway tumors b. Blood pressure measurements at each visit c. Yearly examination of spine for early signs of scoliosis d. A and C e. All of the above

Answer 40

e. All of the above

Question 41

These clinical feature/s is/are virtually pathognomonic of NF1 ## Footnote a. Crowe sign b. Plexiform neurofibroma c. Lisch nodules d. A and C e. C only

Answer 41

Answer D: crowe sign (intertriginous freckling) p. 2465 and lisch nodules p. 2469

Question 42

The following is true regarding NF2 except a. Individuals with NF2 have several café au lait macules, most of the time more than 6 macules with intertriginous freckling b. Approximately 60% of patients present in adulthood with hearing loss, tinnitus or loss of balance c. Children are more apt to present with a noneighth nerve tumor d. Characterized by bilateral vestibular schwannomas, meningiomas ependymomas and gliomas

Answer 42

a. Individuals with NF2 have several café au lait macules, most of the time more than macules with intertriginous freckling Answer: A Individuals with NF-2 may have several café-au-lait spots, but rarely have more than 6; intertriginous freckling is not seen. p. 2472

Question 43

True/False: Pheochromocytoma is clearly associated with NF2 a. True b. False

Answer 43

Answer: B. NF1 p. 2474

Question 44

The following are included in the definite diagnosis of Schwannomatosis in individuals 30 years of age or older, except ## Footnote a. 2 or more intradermal schwannomas, at least 1 with histologic confirmation b. No first degree relative with NF2 c. No germline NF2 mutation d. Diagnostic criteria for NF2 is not fulfilled

Answer 44

Answer: A. p2473 nonintradermal

Question 45

The most commonly identified vascular lesion in patients with NF1 is: a. Renal artery vasculopathy b. Angiokeratoma c. Cerebral infarcts d. Peripheral arterial disease

Answer 45

a. Renal artery vasculopathy

Question 46

Hallmark of NF2 a. Axillary freckling b. Meningioma c. Glioma d. Bilateral vestibular schwannomas

Answer 46

d. Bilateral vestibular schwannomas

Question 47

pattern of inheritance of neurofibromatoses

Answer 47

AD

Question 48

the mutation of the gene encoding for this protein leads to the development of** café-au-lait spots, intertriginous freckling, and macrocephaly**

Answer 48

prouty-related EVH1 domain-containing protein 1 (SPRED1)

Question 49

Of all children ultimately diagnosed with NF-1, 81% will have intertriginous freckling by what age?

Answer 49

6 years

Question 50

benign peripheral nerve sheath tumors that involve single or multiple nerve fascicles, often arising from branches of major nerves

Answer 50

Plexiform neurofibromas ## Footnote They may elicit a “**wormy” sensation on palpation,** as a person feels multiple thickened nerve fascicles.

Question 50

this tumor may arise from plexiform neurofibromas

Answer 50

Malignant peripheral nerve sheath tumors

Question 51

first sign of precocious puberty in patients with chiasmal tumors

Answer 51

Accelerated linear growth

Question 52

slightly raised, well-circumscribed **melanocytic hamartomas of the iris** thought to be virtually pathognomonic of NF-1

Answer 52

Lisch nodules

Question 53

* results in poor formation of the wall and/or floor of the orbit * This congenital mesodermal dysplasia may be, but is not always, clinically apparent, leading to proptosis (from herniation of meninges or brain into the orbit) or enophthalmos.

Answer 53

dysplasia of the wing of the sphenoid bone

Question 54

* characterized by congenital thinning and bowing * tibia is most commonly affected, the femur, humerus and other long bones also may be involved

Answer 54

Dysplasia of a long bone

Question 55

refers to individuals who have manifestations of NF-1, usually café-au-lait macules and neurofibromas, limited to one area of the body.

Answer 55

segmental neurofibromatosis or mosaic NF-1