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Genetic Testing And Genetic Counseling For Neurofibromatosis Type 1 (NF1)

In most cases, a diagnosis of NF1 is made through a clinical diagnosis based on the presence of two or more of the six NIH diagnostic criteria for the disorder. However, sometimes a diagnosis of NF1 can't be made definitively based only on physical signs and symptoms – such as in cases of very young children who have developed café-au-lait spots but no other symptoms.

Advanced Genetic Testing for NF1 at the UAB Medical Genomics Laboratory

In cases where a clinical diagnosis of NF1 is inconclusive or needs to be confirmed, genetic testing is currently available that can diagnose NF1 with 95% sensitivity by sequencing a person's NF1 gene to identify mutations. The UAB Medical Genomics Laboratory offers the most scientifically reliable, leading-edge genetic testing techniques currently available for the diagnosis and characterization of NF1 mutations. This state-of-the-art laboratory performs the highest volume of neurofibromatosis genetic testing in the world.

What is Legius Syndrome?Legius syndrome was discovered in the past several years. It is characterized by having multiple cafe-au-lait spots, and sometime skin fold freckles, indistinguishable from those that occur in NF1. It is not associated with tumors such as neurofibromas, optic gliomas, or malignant peripheral nerve sheath tumors. It is much less common than NF1, so genetic testing for a child with multiple cafe-au-lait spots begins with NF1 testing. If the NF1 test is negative, though, it may be helpful to test for mutation in the SPRED1 gene responsible for Legius syndrome.

Based on a small blood sample from the affected individual, the test provides a full characterization of the NF1 mutation at the genomic DNA level. It's important to understand that while genetic testing can confirm the presence of an NF1 mutation, it can't predict the severity of the disorder. Comprehensive genetic testing for NF1 might be appropriate for the following individuals:

  • People suspected of having NF1 in the presence of only one of the NIH diagnostic criteria (such as very young children who have developed café-au-lait spots but no other symptoms)
  • People who have an unusual (atypical) set of symptoms for NF1
  • Those who want to confirm a clinical diagnosis of NF1
  • People interested in preparing for prenatal testing or pre-implantation diagnosis
  • Distinguishing NF1 from other conditions such as Legius syndrome in children with multiple cafe-au-lait spots
  • The Role of Genetic Counseling

    A genetic counselor – who has specialized training in medical genetics and counseling – can help families make informed decisions about whether genetic testing is right for them. The UAB Neurofibromatosis Program provides access to a team of experienced genetic counselors who can help families learn more about genetic testing for NF1 and provide support to assist in adapting to a new diagnosis.

    Also, a genetic counselor can provide information and guidance in the following key areas:

  • Help you understand how NF1 can be passed down in families and determine your risk of having children with NF1
  • Explain the testing options available to you and discuss the benefits and limits of genetic testing
  • Provide information about specific tests that are available to you if you are pregnant or plan on becoming pregnant (i.E., prenatal testing and pre-implantation genetic diagnosis)
  • Interpret and explain the results of genetic testing for NF1
  • For more information, please contact the UAB Neurofibromatosis Program at 205-934-4983.


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  • Neurofibromatosis Type 2

    Neurofibromatosis type 2 is the less common form of neurofibromatosis. This condition is typically characterized by the development of benign tumors called schwannomas that grow along the eighth cranial nerve, which is responsible for hearing and balance.

    Neurofibromatosis type 2 usually causes hearing loss, tinnitus, and balance problems, particularly when negotiating uneven ground or walking in the dark. Many people with this condition also experience vision problems.

    Neurofibromatosis Type 1 and Type 2 – Mayo ClinicPlay

    Features

    Another form of neurofibromatosis is the condition schwannomatosis, which has features that commonly overlap with neurofibromatosis type 2. However, in schwannomatosis, the tumors develop anywhere in the body apart from the vestibular branch of the eighth cranial nerve. Pain is the main symptom of schwannomatosis, which develops as a schwannoma grows larger and starts to compress nerves.

    In type 2 neurofibromatosis, the symptoms depend on where in the body the tumors develop. The tumors usually affect one ear at first but may eventually affect both ears. Less commonly, a person affected by vestibular schwannomas may experience vertigo-like symptoms, as if the environment around them is moving. Eventually the tumors can cause facial numbness, weakness in the tongue leading to slurring, and facial pain.

    Other features of neurofibromatosis type 2 include non-vestibular schwannomas, cataracts, and meningiomas.

    Epidemiology and cause

    Neurofibromatosis type 2 is less common than type 1 neurofibromatosis and is reported in only about 1 in 35,000 live births. In around half of the cases, this condition is caused by a mutated gene that is passed on from a parent to their child.

    In the other half of cases, the mutation develops sporadically in people with no family history of the condition. These patients can also pass the condition onto their offspring.

    Diagnosis

    A diagnosis of neurofibromatosis type 2 is based on the presence of clinical features of the disease, magnetic resonance imaging (MRI), hearing tests, vision tests, and a genetic test for the NF2 mutation. Prenatal testing can also be performed to check for this mutation and the most commonly used tests include chorionic villus sampling, and amniocentesis.

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