Neurofibromatosis Type 2 is a genetic, Autosomal Dominant condition. Autosomal dominant means that of the two genes, alleles, inherited from a parent only one need be mutated for expression of the traits of NF2.
The mutation can be passed by a parent at fertilization of; 1) germ line the ovum by the sperm, or 2) later in embryonic development. If NF2 started in fetal instead of fertilization development, the point NF2 starts determines how many cells of the body will have damaged NF2 cells. The point of NF2 development, determines how much of the body is at risk of the specific mutation formation an individual has.
Different mutations of NF2, ways the chromosome is broken, determines if a person may only have Bilateral Vestibular Schwannoma, or may also have spinal cord Schwannoma, or brain Meningioma as well. There are dozens of combinations of differences. There are many combinations of possible issues a person may or may not have based on exact mutation. There are over 200 known mutations of the gene.
If an individual has a mutation with the possibility of; Bilateral Vestibular Schwannoma, spinal cord Schwannoma, and brain Meningioma, but developed the NF2 condition late in fetal development, they could potentially only grow Bilateral Vestibular Schwannoma, where children they may eventually have would be at risk of tumor formation in all the three regions their parent did not, at either the same or faster rate of growth and possibly earlier in life.
There are three forms of NF; NF1, NF2 and NF3 also known as Schwannomatosis or SWN. NF1 is associated with a mutation in the NF1 gene on chromosome 17 which results in improper function of the Ras-GTPase pathway. NF2 and Schwannomatosis are both located in genes on chromosome 22 and are a lot closer in the traits expressed, but are associated with different genes along chromosome 22, NF2 is caused by a mutation in the NF2 gene. There are 693 genes on chromosome 22. NF2 results in improper function of the Epidermal Growth Factor Receptor (EGFR) Pathway. Schwannomatosis is caused by a mutation in the SMARCB1 gene (SWI/SNF) or the LZTR1 gene.
All forms of NF are neurological conditions where tumors develop and grow at a particular rate. However, the three forms of NF are otherwise completely different disorders. Tumor types common to specific regions of the body and are typically different for all three forms of NF.
To understand the genetics of NF2, it might help to understand some basics of genetics. DNA (Deoxyribonucleic acid) is a combined series of molecular components in each cell in the body which determines what all living entities will grow to be and have. Within each living creature there are set instructions but as creatures are more complex the DNA has room for variations.
Some of the DNA in humans consists of a combination of structures called genes; that are required for development of new cells as a person grows. New cellular development is also necessary for a healthy immune system.
These genes can be found on different chromosomes in the body are specifically for tumor growth blockers, in the case of people with NF2, if the missing NF2 gene results in the development of the protein called MERLIN. Unfortunately, MERLIN also results in more than tumor growth. When the body develops MERLIN, it is unable to prevent tumor growth which results in different combinations of tumors and locations in different parts of the body. While exposure to items that can cause increased growth of tumors of certain types, and in certain locations in the body, tumors will grow regardless of environmental variables like food or toxins.
NF2 is an autosomal dominant condition when inherited from family members. However, NF2 can also occur as a new, Spontaneous Mutation.
An autosomal dominant genetic condition can be passed down through families. This method of inheritance does not "skip" a generation. If a condition is inherited by an autosomal dominant manner it means an individual only need to get the gene from one parent, if a parent has an autosomal dominant condition.
The inheritance of a condition, disorder or trait depends on two main things, the type of chromosome it's on and the kind of trait it is. The trait could be a gene on one of the first 22 chromosomes called autosomal or on a sex chromosome, X or Y, the 23rd chromosome. The second thing the inheritance depends on is the type of trait, a dominant or recessive one.
The following is the explanation for the Autosomal Dominance chart.
A few factors are responsible for the rate a parent has of having a child with NF2.
It is not uncommon for NF to also be a result of a Spontaneous Mutation, also known as de novo mutation (New Mutation). In a Spontaneous Mutation, there is no family history of NF2. Approximately 50% of NF patients' doctors see, have it as a result of a Spontaneous Mutation.
Frequently in Sporadic Mutations of NF2; Mosaicism occurs. People with a Mosaic mutation of a genetic condition; do not have the mutation in every cell in their body.
Initially it was believed there were two forms of NF2; Wishart and Gardner, understanding of genetics proved that NF2 is a lot more complicated than just two forms and is now understood to be up to 200 mutations of NF2 due to how the body reacts to the missing or mutated NF2 gene. Wishart was said to be the milder form than Gardner. Also, the same severity of NF2 within a family assumes for autosomal dominant inheritance and not as a Spontaneous mutation, this means if a child will have similar growth rate and issues as family, assuming the family with NF2 was not Mosaic and had NF2 in every cell in their body.
An individual, who has NF2 through spontaneous mutation, may be mosaic and might not have NF2 in their entire body depending on when in embryonic development the NF2 mutation occurred. These individuals might have more of a mild case then their children.
Some of the other variations and mutations include:
Sporadic VS, VS not a result of NF2, are very uncommon in young children, at or before adolescence. Sporadic VS are more common by the 4th or 5th generation.
Sporadic VS and NF2 VS are both generally benign, Spontaneous VS damage hearing in one ear, not both like NF2, but like NF2 also result in tinnitus, possible facial paralysis and life threatening neurological symptoms if not surgically managed.[Chen, 2014]
Individuals who are born with Ring Chromosome 22; may also develop NF2, as a result of damage to the 22nd chromosome.
Ring 22 is not a result of NF2, it is the result of a poor formation of the entire twenty second Chromosome that has many issues, but can result in NF2 as well as all the other issues associated with it.
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