Chapter 22 - Neurofibromatosis

Figure 22.B02: Diagnostic Criteria for Neurofibromatosis Type 2

Confirmed (Definite) Neurofibromatosis Type 2 1. Bilateral vestibular schwannomas --> (VS aka acoustic neuroma) Presumptive (Probable) Neurofibromatosis Type 2 1. Family history of neurofibromatosis type 2 (first-degree family member or relative) plus: 2. Unilateral VS OR any two of the following: 1. Meningioma 2. Posterior subcapsular lenticular opacity 3. Glioma 4. Cortical cataract 5. Schwannoma

Figure 22.F01: Body systems affected by neurofibromatosis type 1. note the signs: 1. freckling where skin meets skin ( armpits, groin, under breast) 2. speech impairment 3. oversized head 4. early or delayed puberty 5. high BP

note the signs: 1. freckling where skin meets skin ( armpits, groin, under breast) 2. speech impairment 3. oversized head 4. early or delayed puberty 5. high BP

Diagnostic Criteria for Neurofibromatosis Type 1

Two or more of the following must be present: 1. Six or more café-au-lait spots 0.5 cm or larger in prepubertal individuals, 1.5 cm or larger in postpubertal individuals 2. Two or more neurofibromas of any type or one or more plexiform neurofibromas 3. Freckling in the axillary or inguinal region 4. Optic glioma (tumor of the optic pathway) 5. Two or more Lisch nodules (benign iris hamartomas) 6. A distinctive bony lesion: dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex 7. A first-degree relative with neurofibromatosis type 1

1. what is a neurofibroma 2. These neurofibromas grow where? 3. how many cafe'-au-lait spots and of what size are considered to be dx of NF?

1. A neurofibroma is a benign, encapsulated tumor resulting from proliferation of Schwann cells that are of ectodermal origin and form a continuous envelope around each nerve fiber of peripheral nerves --> starts ar the roots and extends distally 2. on nerves in the whole body in a condition called Neurofibromatosis (NF) 3. 6+ that are 1.5 cm in diameter

Genetics of NF-1: 1. AKA? 2. mode of inheritance? 3. Mutation in NF1 gene on chromosome ___ that codes for _______? 4. A non-mutated NF1 gene what kind of gene? 5. The mutation leads to lack of what?

1. AKA von Recklinghausen disease 2. Autosomal dominant 3. Mutation in NF1 gene on chromosome 17 that codes for neurofibromin 4. a tumor suppressor gene 5. lack of tumor suppression = growth of neurofibromas

Genetics of NF-2: 1. mode of inheritance? 2. Mutation of NF2 gene on chromosome ___ that encodes for _____ 3. T/F Merlin is a tumor suppressor gene 4. Mutation disrupts merlin activity and leads to formation of what?

1. Autosomal dominant 2. Mutation of NF2 gene on chromosome 22 that encodes for merlin 3. True 4. schwannomas

Neurofibromatosis Overview: 1. what is the mode of inheritance 2. Affects males and females of what ethnic groups 3. 50% affected have what kind of history pertaining to this conditon? 4. which mutation is MC? (NF-1 / NF-2)

1. Autosomal dominant inheritance 2. Affects males and females of all races and ethnic groups 3. 50% affected have prior family history and 50% appear to be the first case in their family 4. NF-1 (more common)

Management for Neurofibromatosis: 1. what is the known cure? 2. Early detection of treatable complications need to be managed how? 3. Complete thorough examination how often? 4. what imaging modalities are used to assess for signs and symptoms of neurological problems (2) 5. MRI for patients with NF-2 is indicated for pt of what age? 6. Regular slit lamp examinations for those with (NF-2 /NF-1)

1. No cure 2. Surgery referral for removal of neurofibromas 3. Complete thorough examination annually 4. CT/MRI for signs and symptoms of neurological problems 5. MRI for patients with NF-2 in early adolescence 6. Regular slit lamp examinations for those with NF-2

Diagnosis for neurofibromatosis: 1. T/F Mutation analysis is fairly accurate but not widely available 2. T/F Family history and careful physical examination are needed for diagnosis 3. Café-au-lait spots will develop when? 4. In children between the ages of 5 and 12, the presence of café-au-lait macules greater than________ in diameter is highly suggestive of_________

1. True 2. True 3. first 3 years of life and neurofibromas form in adolescence 4. greater than 0.5 cm in diameter is highly suggestive of NF

NF-1 1. T/F Learning disabilities and mental retardation may occur in NF-1 2. what else may also be present (3)

1. True 2.Endocrine disorders, short stature, and growth hormone deficiency

Chapter Summary for Neurofibromatosis: 1. The autosomal dominant genetic disorder known as neurofibromatosis causes tumors to grow on the covering of the nerves anywhere in the body at any time. 2. Type 1 neurofibromatosis is the most common variant of this disease; it is characterized clinically by the combination of patches of hyperpigmentation and cutaneous and subcutaneous tumors. 3. Type 2 neurofibromatosis is characterized by the development of noncancerous tumors called schwannomas on the nerves that control hearing and balance. 4. There is no cure for type 1 neurofibromatosis, so medical management is limited to the early detection of treatable complications. 5. Neurofibromatosis type 1, also called von Recklinghausen disease, is caused by a mutation in the NF1 gene located on chromosome 17, which encodes for neurofibromin. 6. Type 2 neurofibromatosis is caused by a mutation in the NF2 gene located on chromosome 22, which encodes for merlin.

Chapter Summary for Neurofibromatosis: 1. The autosomal dominant genetic disorder known as neurofibromatosis causes tumors to grow on the covering of the nerves anywhere in the body at any time. 2. Type 1 neurofibromatosis is the most common variant of this disease; it is characterized clinically by the combination of patches of hyperpigmentation and cutaneous and subcutaneous tumors. 3. Type 2 neurofibromatosis is characterized by the development of noncancerous tumors called schwannomas on the nerves that control hearing and balance. 4. There is no cure for type 1 neurofibromatosis, so medical management is limited to the early detection of treatable complications. 5. Neurofibromatosis type 1, also called von Recklinghausen disease, is caused by a mutation in the NF1 gene located on chromosome 17, which encodes for neurofibromin. 6. Type 2 neurofibromatosis is caused by a mutation in the NF2 gene located on chromosome 22, which encodes for merlin.

Chapter review questions: 1. ___ neurofibromas is the MC variant and is characterized clinically by the combination of patches of hyperpigmentation and cutaneous and subcutaneous tumors a. Type 1 2. Type 2 neurofibromatosis is characterized by the development of noncancerous tumors called ___ on the nerves that control hearing and balance. a. Schwannomas 3. Loss of tumor suppression due to NF1 mutation presumably permits uncontrolled ___ which leads to the formation of neurofibromas a. Ras activation 4. T or F; the presence of multiple café au lait spots proves that a patient has NF 1 a. False 5. Neurofibromatosis is a/an ___ genetic condition and approximately 50% of those affected have a family history of this disorder. a. AD 6. _________ is/are associated with neurofibromatosis type 1, whereas __________ is/are associated with neurofibromatosis type 2. a. Spinal tumors ; Optic glioma b. Schwannomas ; Freckling where skin meets armpits c. Café-au-lait spots ; Cataracts at young age Meningioma ; Bilateral acoustic neuromas

Chapter review questions: 1. ___ neurofibromas is the MC variant and is characterized clinically by the combination of patches of hyperpigmentation and cutaneous and subcutaneous tumors a. Type 1 2. Type 2 neurofibromatosis is characterized by the development of noncancerous tumors called ___ on the nerves that control hearing and balance. a. Schwannomas 3. Loss of tumor suppression due to NF1 mutation presumably permits uncontrolled ___ which leads to the formation of neurofibromas a. Ras activation 4. T or F; the presence of multiple café au lait spots proves that a patient has NF 1 a. False 5. Neurofibromatosis is a/an ___ genetic condition and approximately 50% of those affected have a family history of this disorder. a. AD 6. _________ is/are associated with neurofibromatosis type 1, whereas __________ is/are associated with neurofibromatosis type 2. a. Spinal tumors ; Optic glioma b. Schwannomas ; Freckling where skin meets armpits c. Café-au-lait spots ; Cataracts at young age Meningioma ; Bilateral acoustic neuromas

NF-1 and NF-2 Overview: NF-1 1. are Tumors of what? (2) 2. Hamartoma in the iris of the eye is called what? ) 3. Axillary freckling is aka what sign 4. Bone involvement may be present as what? 5. T/F Gliomas of optic nerve may occur NF-2 1. Noncancerous tumors called schwannomas can even grow on what nerves? (2) 2. May not experience symptoms until what age? 3. this mutations is likely to have (many/Few) cutaneous manifestations

NF-1 1. subcutaneous tissues and café-au-lait spots 2. (Lisch nodule) 3. (Crowe sign) 4. as pseudoarthrosis of the tibia, --> bowing of long bones, and orbital defects 5. True NF-2 1. auditory and vestibular nerves --> Bilateral but not necessarily at the same times so varying hearing loss 2. 40s and 50s 3. Few cutaneous manifestations

Figure 22.F02: Body systems affected by neurofibromatosis type 2. note the signs: 1. spinal tumors 2. hearing loss 3. cataracts at young age 4. meningioma 5. bilateral vestibular schwannomas 6. balance problems 7. general muscle wasting

note the signs: 1. spinal tumors 2. hearing loss 3. cataracts at young age 4. meningioma 5. bilateral vestibular schwannomas 6. balance problems 7. general muscle wasting