It has some NIH website related information and others. A small presentation that compiles a lot basic and recent data on Neurofibromatosis and Schwannomatosis. Any questions, suggestions or comments do email me.

1. NF1, NF2 and
Schwannomatosis
- Dr. Priyanka Sharma
-
priyankasharmamds@gmail.com
P.S. Download for animation and detailed explanation

2. Context
 Neurofibromatosis & Types
 Symptoms for NF1 and NF2
 Schwannomatosis & Symptoms
 More information and treatment management
 Role of genetics
 Prenatal test and genetic testing available
 Few research findings – need of underrepresented communities
 Encouraging population to be part of research for more information in
future!
 Conclusion and References

3. The neurofibromatoses are a
group of three genetically
distinct disorders that cause
tumors to grow in the nervous
system.
Tumors begin in the
supporting cells that make up
the nerve and the myelin
sheath.
Schwann
Cells
NF1/von Recklinghaus
disease
The most common nerve-
associated tumors in NF1 are
neurofibromas (tumors of the
peripheral nerves).
NF2/ Vestibular
Schwannomas
NF2 is the presence of slow-
growing tumors on the eighth
cranial nerves.
https://www.slideshare.net/drpriyankaclre/cranial-nerves-priyanka-sharma-
seminar

4. Schwannomatosis
Schwannomas develop when
Schwann cells, which are
specialized cells that
normally form an insulating
layer around the nerve, grow
uncontrollably to form a
tumor.
Schwannomatosis
Signs and symptoms
of schwannomatosis usually
appear in early adulthood.
Schwannomatosis
The most common symptom
is long-lasting (chronic) pain,
which can affect any part of
the body. In some cases, the
pain is felt in areas where
there are no known tumors.
Schwannomatosis
Other signs and symptoms
that can occur
with schwannomatosis depen
d on the location of the
tumors and which nerves are
affected. These problems
include numbness, weakness,
tingling, and headaches.

5. NF1 NF2 Schwannomatosis
Incidence 1 in 30,000 to 40,000 in
US
1 IN 25,000 in US 1 in 40,000 to 1 in 1.7
million people in US
Other Names • Neurofibromatosis 1
• NF1
• Peripheral
Neurofibromatosis
• Recklinghausen
Disease, Nerve
• von Recklinghausen
Disease
• BANF
• Bilateral Acoustic
Neurofibromatosis
• Central
Neurofibromatosis
• Familial Acoustic
Neuromas
• Neurofibromatosis 2
• Neurofibromatosis
Type II
• Nf2
• Schwannoma,
Acoustic, Bilateral
• Multiple
Neurilemmomas
• Multiple
Schwannomas
• Neurilemmomatosis
• Neurilemmomatosis,
Congenital Cutaneous
• Neurinomatosis
• Neurofibromatosis
Type 3
Age group Symptoms appear at
birth or by the time
child is 10 years
18-22 years or
Unilateral Vestibular
schwannoma before age
30 years
30-60 years, though
they can occur at
any age

6. Treatment Management
NF1 NF2 Schwannomatosis
Medication In April 2020 – FDA
approved Selumetinib
(Koselugo) for
treatment of children
2years or more. It stops
the tumor cells from
growing.
BXCL101 is a proprietary
version of an approved
drug, bortezomib?
(Need more
information)
No medication as such
other than pain
management.
Surgical Yes with sometimes
radiation and
chemotherapy.
Removal of NF2 tumor
when small.
Implant placement:
- Cochlear implant
- Auditory brainstem
implant.
Yes if possible. If not
the observation,
periodic imaging, and
pain management.

7. Role of Genetics
Neurofibromatosis I Neurofibromatosis II Schwannomatosis
Autosomal dominant pattern of inheritance An autosomal dominant pattern of
inheritance
Most cases of schwannomatosis are
sporadic, which means that they occur in
people with no history of the disorder in
their family.
People with this condition are born with one
mutated copy of the NF1 gene in each cell.
Some people with
sporadic schwannomatosis have mutations
in the SMARCB1 or LZTR1 gene, but in
others, the cause of the condition is
unknown.
In about half of cases, the altered gene is
inherited from an affected parent
In about half of cases, the altered gene is
inherited from an affected parent
Studies suggest that 15 to 25 percent of
cases of schwannomatosis run in families.
The remaining cases result from new
mutations in the NF2 gene and occur in
people with no history of the disorder in
their family.
The remaining cases result from new
mutations in the NF2 gene and occur in
people with no history of the disorder in
their family.
An autosomal dominant pattern of
inheritance, which means a mutation in
one copy of the SMARCB1 or LZTR1 gene in
each cell greatly increases the risk of
developing schwannomas.
The NF1 gene, located on 17q11.2, encodes
for a protein also known as neurofibromin.
The NF2 gene is located on 22q12.2 and
encodes for merlin (schwannomin).
The most common somatic mutations in
schwannomas are mutations in
the NF2 gene and a loss of chromosome
22 (which is the chromosome on which
the SMARCB1, LZTR1, and NF2 genes are
found).

8. Are there prenatal tests for the neurofibromatosis?
 Clinical genetic testing can confirm the presence of a mutation in the NF1 gene.
 Prenatal testing for the NF1 mutation is also possible using amniocentesis or chorionic villus sampling
procedures.
 Genetic testing for the NF2 mutation is sometimes available, but is accurate only in about 65 percent of
those individuals tested.
 Prenatal or genetic testing for Schwannomatosis currently does not exist.
 Molecular Genetic Testing for Schwannomatosis:
 Linkage analysis
 Targeted variant analysis
 Sequence analysis of the entire coding region
 Deletion/duplication analysis
 Sequence analysis of select exons
https://www.ncbi.nlm.nih.gov/gtr/conditions/C3810283/

9. Some Research findings
 After literature search - Indigenous peoples, including American Indians (AI), Alaska Natives (AN), and
Native Hawaiians (NH), remain underrepresented and understudied in genetic and clinical health
research, despite facing disproportionately higher rates of tumors compared with non- Hispanic whites.
- Ref: Katrina G. Claw et al, A framework for enhancing ethical genomic research with Indigenous
communities. Nature Communications | (2018) 9:2957
 According to a cross-sectional study on racial/ethnic differences in pediatric brain tumor diagnoses in
Patients with Neurofibromatosis Type 1 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4784699/)
Frequency Of Pediatric Brain Tumor Diagnoses Among Patients With NF1
Less likely More likely Explanation
Individuals with African ancestry
and possibly Asian ancestry
European ancestry Explained by genetic, environmental, or social
factors or a combination of these factors that
correlate with race/ethnicity.
Optic gliomas - Social Factors
Lower MRI screening rate for optic
gliomas in Blacks
Higher MRI Screening
rate in Whites
Optic gliomas are often asymptomatic and may
never come to the attention of a physician in
the absence of a MRI scan or ophthalmology
evaluation. Therefore, access to care and
particularly an NF specialist could explain
differences in the frequency of pediatric brain
tumor diagnoses by race.

10. Encourage population for research
Letting patients know that:
The importance of ancestry and diversity with regards to these rare
disorders.
Research findings from our data base on such rare disorders would
 Contribute to the body of scientific knowledge
 Revealing new biological causes
 May lead to new ways to treat these disorders

11. Conclusion
Using diagnostic imaging, eye examinations, hearing and balance tests,
neurological examination, blood and genetic testing and quality of life
assessment – Researchers hope to better characterize the impact of NF
and Schwannomatosis on individuals and look for possible factors that
may effect disease progression.
References:
https://ghr.nlm.nih.gov/condition/schwannomatosis#inheritance
https://ghr.nlm.nih.gov/condition/neurofibromatosis-type-1#
https://ghr.nlm.nih.gov/condition/neurofibromatosis-type-2#synonyms