21 - 135 - NEUROFIBROMATOSES Flashcards
Softer than the surrounding connective tissue and protrude just above the skin surface or lie just under the skin with an overlying violaceous hue.
Cutaneous neurofibromas
■ Arise from peripheral nerves, both under the skin and deep in the viscera.
■ Generally much harder.
Subcutaneous neurofibromas
■ 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.
Plexiform neurofibromas
■ 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.
Mosaic neurofibromatosis Type 1 (segmental NF-1)
Diagnostic Criteria for Neurofibromatosis Type 1
Diagnostic Criteria for Neurofibromatosis Type 1
protrude just above the skin surface or lie just under the skin with an overlying violaceous hue
Cutaneous neurofibromas
They are softer than the surrounding connective tissue, often creating a “buttonholing” sensation when a finger is rubbed gently over the surface
e benign peripheral nerve sheath tumors that involve single or multiple nerve fascicles, often arising from branches of major nerves.
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).
arise from peripheral nerves, both under the skin and deep in the viscera, are generally much harder
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.
Diagnostic Criteria for Neurofibromatosis Type 2
These are often the first manifestation of NF-1 to appear.
Café-au-lait spots, which are flat, pigmented macules
Café-au-lait spots smaller than 5 mm are referred as
freckles
commonly present in the axillae, inguinal region, and under the breasts
freckles seen in NF1 are commonly present in what locations
commonly present in the axillae, inguinal region, and under the breasts
What do you call the presence of axillary (armpit) freckling in people with neurofibromatosis type I (von Recklinghausen’s disease)?
Crowe sign
lesions are not related to sun exposure, and are considered virtually pathognomonic of NF-1
period of greatest risk for the development of symptomatic optic pathway tumors in NF-1 is during the first how many years of life?
first 6 years of life
2 bony lesions distinctive enough to be included in the diagnostic criteria for NF-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.
- Dysplasia of a long bone, characterized by congenital thinning and bowing, affects approximately 2% of children with NF-1
most common long bone affected in NF1
tibia
femur, humerus and other long bones also may be involved
- 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.
Hallmark of NF-2
presence of bilateral vestibular schwannomas
characteristic cutaneous lesion of NF-2 is
cutaneous schwannoma
More than 50% of children with Noonan syndrome have cardiovascular disease, most commonly _________
pulmonary valve stenosis
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
LEGIUS SYNDROME
develop multiple schwannomas but who fail to develop other manifestations of NF-2, particularly vestibular schwannomas
SCHWANNOMATOSIS
Current diagnostic criteria for a definite diagnosis of schwannomatosis in individuals 30 years of age or older include:
(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.
most common skeletal manifestation of NF-1, affecting 10% to 30% of patients
Scoliosis
The most commonly identified vascular lesion in patients with NF-1 is in what artery?
renal artery, leading to renovascular hypertension
NF-1 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
A
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
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
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
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: C. table 135-1 p. 2466
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
e. All of the above
These clinical feature/s is/are virtually pathognomonic of NF1
a. Crowe sign
b. Plexiform neurofibroma
c. Lisch nodules
d. A and C
e. C only
Answer D: crowe sign (intertriginous freckling) p. 2465 and lisch nodules p. 2469
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
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
True/False: Pheochromocytoma is clearly associated with NF2
a. True
b. False
Answer: B. NF1 p. 2474
The following are included in the definite diagnosis of Schwannomatosis in individuals 30 years of age or older, except
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: A. p2473 nonintradermal
The most commonly identified vascular lesion in patients with NF1 is:
a. Renal artery vasculopathy
b. Angiokeratoma
c. Cerebral infarcts
d. Peripheral arterial disease
a. Renal artery vasculopathy
Hallmark of NF2
a. Axillary freckling
b. Meningioma
c. Glioma
d. Bilateral vestibular schwannomas
d. Bilateral vestibular schwannomas
pattern of inheritance of neurofibromatoses
AD
the mutation of the gene encoding for this protein leads to the development of** café-au-lait spots, intertriginous freckling, and macrocephaly**
prouty-related EVH1 domain-containing protein 1 (SPRED1)
Of all children ultimately diagnosed with NF-1, 81% will have intertriginous freckling by what age?
6 years
benign peripheral nerve sheath tumors that involve single or multiple nerve fascicles, often arising from branches of major nerves
Plexiform neurofibromas
They may elicit a “wormy” sensation on palpation, as a person feels multiple thickened nerve fascicles.
this tumor may arise from plexiform neurofibromas
Malignant peripheral nerve sheath tumors
first sign of precocious puberty in patients with chiasmal tumors
Accelerated linear growth
slightly raised, well-circumscribed melanocytic hamartomas of the iris thought to be virtually pathognomonic of NF-1
Lisch nodules
- 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.
dysplasia of the wing of the sphenoid bone
- characterized by congenital thinning and bowing
- tibia is most commonly affected, the femur, humerus and other long bones also may be involved
Dysplasia of a long bone
refers to individuals who have manifestations of NF-1, usually café-au-lait macules and neurofibromas, limited to one area of the body.
segmental neurofibromatosis or mosaic NF-1
