Neurofibromatosis (NF) is a set of complex genetic disorders that can affect almost every organ system, causing a predisposition for tumors to grow on nerves in the brain and throughout the body.
Listen as Stephanie Morris, MD explains that while there is no cure for NF1, research throughout the world is providing hope that new treatments and management strategies will eventually transform the practice of medicine for people affected with NF1.
The Neurofibromatosis Comprehensive Care Team at St. Louis Children's Hospital provides detailed patient assessments and works with referring physicians, allied health professionals and agencies to deliver state-of-the-art medical services both locally and nationally.
Neurofibromatosis Type 1
Featured Speaker:
Learn more about Stephanie Morris, MD
Stephanie Morris, MD
Stephanie Morris, MD is a Washington University pediatric neurologist at St. Louis Children’s Hospital.Learn more about Stephanie Morris, MD
Transcription:
Neurofibromatosis Type 1
Melanie Cole (Host): Neurofibromatosis is a genetic disorder that affects 1 in every 3,000 people. It is a condition characterized by changes in skin color, and the growth of tumors along nerves in the skin, brain, and other parts of the body. My guest today is Dr. Stephanie Morris. She’s a Washington University Pediatric Neurologist at St. Louis Children’s Hospital. Welcome to the show, Dr. Morris. What is neurofibromatosis?
Dr. Stephanie Morris (Guest): Thank you, so much. Neurofibromatosis Type One or NF-1 is a common inherited neurologic condition that causes benign tumors grow in the brain and on the nerves throughout the body. It occurs in approximately 1 in every 3,000 people, and it’s actually more common than Cystic Fibrosis, and Hereditary Muscular Dystrophy combined. It’s sometimes referred to as Von Recklinghousen’s Disease, but this isn’t a term that we don’t use anymore.
NF-1 is a genetic disorder. It’s caused by mutations in the NF-1 Gene. All patients have two copies of the NF-1 Gene. They get one from their mother and one from their father, and when one of those copies is altered, it doesn’t work properly anymore, and it causes NF-1. Half of children inherit the condition from a parent. It can be either their mother or their father, while the other half have a new mutation in their gene that likely occurred in the sperm or the egg that created the child.
Sometimes the parent is so mildly affected, though, that they don’t know that they have NF-1, so it’s important for parents to be thoroughly examined by a doctor familiar with NF-1 when a child is diagnosed. If a parent has NF-1, there’s about a 50% chance with each pregnancy that their child will have NF-1.
Melanie: Are there some disorders that are similar to those of NF-1?
Dr. Morris: There are some similar disorders. Probably the most similar is a disorder called Legius Syndrome. This is also a genetic condition, but it’s caused by mutations in a completely different gene called the SPRED-1 Gene. People who have Legius Syndrome typically just present with changes to their skin, birthmarks, and specific freckling. There are also some other disorders, such as McCune-Albright Syndrome, as well as Noonan’s Syndrome where these patients can have also very similar features that are caused by mutations in different genes.
Melanie: Dr. Morris, when might a clinical diagnosis of NF-1 be made?
Dr. Morris: Sure, so there are lots of different features of NF-1, and the NIH has established specific diagnostic criteria. A patient has to have two or more of those diagnostic criteria in order to be diagnosed with NF-1. The diagnostic criteria for NF-1 include the presence of multiple darkly colored birthmarks, which we call café au lait spots. It also includes freckling in specific areas of the body such as the armpits or the groin. People can sometimes have neurofibromas, which are small, benign tumors that grow on the peripheral nerves of the body and are characteristic of NF-1. Sometimes these can look like fleshy masses on the skin, others look like little purplish pits in the skin, and some simply feel like a hard nodule under the skin. Another tumor that’s seen in NF-1 is called the Plexiform Neurofibroma. These are much larger, benign tumors that typically involves a network or a bundle of nerves. They can sometimes be very large and are very difficult to remove because of their extensive involvement of the skin, the muscle, the nerves, and bone.
Other signs of NF-1 include the development of a tumor involving the nerves that connect the eye to the brain called an Optic Pathway Glioma. Patients can sometimes have very distinct bone abnormalities, such as abnormal development of the lower leg called tibial dysplasia, or abnormal development of the eye socket, called orbital dysplasia. These features typically develop in infancy and can lead to serious complications such as blindness and poorly healing broken bones, which can sometimes lead to amputation of an extremity. And then, of course, having a first-degree family member, since this is an inherited condition, can also lead to the diagnosis of NF-1.
Melanie: So what’s the general prognosis? What do you generally tell other pediatricians about what they can expect with NF-1?
Dr. Morris: Sure. NF-1 is a very unpredictable disorder. The symptoms vary widely from one person to another and can even differ between two people in the same family who actually share the exact same gene mutation. Some people are only very mildly affected with only skin changes, such as the darkly pigmented birthmarks, the café au lait spots, freckling, and only a few neurofibromas, while some patients have major medical problems such as vision loss, epilepsy, and cancer-related to NF-1. Right now it’s actually very difficult to predict how severely affected a newly diagnosed child with NF-1 will be. For this reason, it’s important for children with NF-1 to be seen regularly by an NF-1 specialist who can monitor for new signs and complications of NF-1.
There’s no cure for NF-1, and currently, all the treatment for NF-1 is reactive such that if an NF-1-related complication arises, such as vision loss, scoliosis, painful or disfiguring neurofibromas, or concerns for cancer, patients are typically referred to the appropriate specialist who are experiencing caring for individuals with NF-1.
In addition to the physical manifestations of NF-1, children can also show signs of academic difficulty, ADHD, autism, and other developmental delays. These children are typically referred for formal neuropsychological testing and are treated appropriately with the initiation of individualized education plans at schools, treatment with certain medications, or referral for specific therapy services to improve their academic and long-term success.
Melanie: When would you like to have pediatricians refer to a specialist such as yourself?
Dr. Morris: Yeah, that’s a great question. Café au lait spots are actually very common in the general population with nearly 10% of people having one to two café au lait spots, however if a child is identified as having three or more café au lait spots, they really should be referred to see a doctor who specializes in diagnosing and caring for people with NF-1. If a child has any other feature associated with NF-1 regardless of the number of birthmarks, they should similarly be referred.
Melanie: And you spoke just a bit about treatments. What are some other standard therapies that you might use for a child with NF-1?
Dr. Morris: Yeah, that’s a good question. Right now, the therapies that we use to treat children with NF-1 are actually quite limited. For children who have neurofibromas that are disfiguring or uncomfortable, we typically will refer them to plastic surgeons who are experienced in removing the tumors. Children who have very large plexiform neurofibromas that cause bony problems, such as unequal leg lengths or scoliosis will often be referred to Orthopedic Surgeons so that they can have surgical procedures to improve the stability of their bones and correct the underlining bony deformity. Children who have optic pathway tumors – these are the tumors that grow on the nerve that connects the eye to the brain – sometimes require chemotherapy to treat the underlying tumor that may affect vision.
There are several clinical trials that are currently ongoing looking at different therapeutic agents that could address some of the complications of NF-1. However, they’re not currently clinically available and are only available for eligible patients.
Melanie: And you mentioned a bit about this before, but I’d like you to expand a little bit on how the patient is affected in the long-term, and you mentioned autism, ADHD, ADD, so what do you want other Pediatrician – and even parents to know about what they can expect, or what they can look for, or red flags as the child grows?
Dr. Morris: Sure. The most common long-term problems associated with NF-1 are really physical disfigurement related to the growth of tumors over time and cognitive-behavioral problems including learning disabilities, ADHD, and autism, which can lead to school failure and problems with maintaining friendships and personal relationships. Other severe symptoms or complications related to NF-1 that can affect a patient in the long-term include mood disorders, such as anxiety and depression, sleep problems, chronic pain, and even early death related to increased risk for cancer later in life.
The things that parents and Pediatricians should really be looking for are problems with academic success. Children who tend to do well in Kindergarten and first grade, sometimes will drop off the curve around second or third grade and start to have greater difficulties in school. Problems with initiating and maintaining friendships can sometimes be a red flag. Any child who has a tumor who all of a sudden develops, weakness in that extremity, significant pain associated with that tumor, or changes to the texture or color of the tumor should be immediately referred for evaluation of development into cancer.
Melanie: So wrap it up for us, Dr. Morris. Give Pediatricians your best advice about recognizing NF-1 and tell us about your team. Why is St. Louis Children’s Hospital so great to work with?
Dr. Morris: Sure. Pediatricians really should be looking at all infants who come through their door for any characteristic birthmarks. If they see a child that has three or more birthmarks – these are darkly-colored birthmarks that can range in color from light to very dark brown – they should think of NF-1 as a possible diagnosis. We are always happy to see kids in evaluation in infancy through early adulthood for evaluation of these birthmarks. It’s certainly possible that we won’t be able to secure the diagnosis of NF-1 right away if they have just a few birthmarks. However, we will continue to follow that child every year for every year to make sure that they don’t develop a second symptom suggestive of the diagnosis of NF-1.
We also now have clinical genetic testing available, and so if a parent or Pediatrician is particularly concerned about the diagnosis, we’re able to send blood to be tested for specific NF-1 mutations, which could also confirm the diagnosis. Additionally, if there are any other children who develop unusual features, such as an optic pathway glioma, freckling under their arms or their groin, or if they have unusual bowing of their legs or very progressive scoliosis – and maybe they only have a couple of birthmarks, these are also kids that Pediatricians should be thinking about as having possible diagnosis of NF-1 and should refer them for evaluation.
We have a fantastic comprehensive NF-1 clinic here at the Washington University School of Medicine. We have myself as well as a Neurologist, Dr. David Gutmann, who is the Director of the NF Clinical Program. We also have dedicated Physical Therapists, speech therapists, orthotists, as well as clinical research assistants who help us both with clinical care as well as with clinical and basic research dedicated to treating those with NF-1.
Melanie: Thank you, so much, Dr. Morris for being with us today. A physician can refer a patient by calling Children’s Direct Physician Access Line at 1-800-678-HELP, that’s 1-800-678-4357. You’re listening to Radio Rounds with St. Louis Children’s Hospital. For more information on resources available at St. Louis Children’s Hospital, you can go to StLouisChildrens.org, that’s StLouisChildrens.org. This is Melanie Cole. Thanks, so much, for listening.
Neurofibromatosis Type 1
Melanie Cole (Host): Neurofibromatosis is a genetic disorder that affects 1 in every 3,000 people. It is a condition characterized by changes in skin color, and the growth of tumors along nerves in the skin, brain, and other parts of the body. My guest today is Dr. Stephanie Morris. She’s a Washington University Pediatric Neurologist at St. Louis Children’s Hospital. Welcome to the show, Dr. Morris. What is neurofibromatosis?
Dr. Stephanie Morris (Guest): Thank you, so much. Neurofibromatosis Type One or NF-1 is a common inherited neurologic condition that causes benign tumors grow in the brain and on the nerves throughout the body. It occurs in approximately 1 in every 3,000 people, and it’s actually more common than Cystic Fibrosis, and Hereditary Muscular Dystrophy combined. It’s sometimes referred to as Von Recklinghousen’s Disease, but this isn’t a term that we don’t use anymore.
NF-1 is a genetic disorder. It’s caused by mutations in the NF-1 Gene. All patients have two copies of the NF-1 Gene. They get one from their mother and one from their father, and when one of those copies is altered, it doesn’t work properly anymore, and it causes NF-1. Half of children inherit the condition from a parent. It can be either their mother or their father, while the other half have a new mutation in their gene that likely occurred in the sperm or the egg that created the child.
Sometimes the parent is so mildly affected, though, that they don’t know that they have NF-1, so it’s important for parents to be thoroughly examined by a doctor familiar with NF-1 when a child is diagnosed. If a parent has NF-1, there’s about a 50% chance with each pregnancy that their child will have NF-1.
Melanie: Are there some disorders that are similar to those of NF-1?
Dr. Morris: There are some similar disorders. Probably the most similar is a disorder called Legius Syndrome. This is also a genetic condition, but it’s caused by mutations in a completely different gene called the SPRED-1 Gene. People who have Legius Syndrome typically just present with changes to their skin, birthmarks, and specific freckling. There are also some other disorders, such as McCune-Albright Syndrome, as well as Noonan’s Syndrome where these patients can have also very similar features that are caused by mutations in different genes.
Melanie: Dr. Morris, when might a clinical diagnosis of NF-1 be made?
Dr. Morris: Sure, so there are lots of different features of NF-1, and the NIH has established specific diagnostic criteria. A patient has to have two or more of those diagnostic criteria in order to be diagnosed with NF-1. The diagnostic criteria for NF-1 include the presence of multiple darkly colored birthmarks, which we call café au lait spots. It also includes freckling in specific areas of the body such as the armpits or the groin. People can sometimes have neurofibromas, which are small, benign tumors that grow on the peripheral nerves of the body and are characteristic of NF-1. Sometimes these can look like fleshy masses on the skin, others look like little purplish pits in the skin, and some simply feel like a hard nodule under the skin. Another tumor that’s seen in NF-1 is called the Plexiform Neurofibroma. These are much larger, benign tumors that typically involves a network or a bundle of nerves. They can sometimes be very large and are very difficult to remove because of their extensive involvement of the skin, the muscle, the nerves, and bone.
Other signs of NF-1 include the development of a tumor involving the nerves that connect the eye to the brain called an Optic Pathway Glioma. Patients can sometimes have very distinct bone abnormalities, such as abnormal development of the lower leg called tibial dysplasia, or abnormal development of the eye socket, called orbital dysplasia. These features typically develop in infancy and can lead to serious complications such as blindness and poorly healing broken bones, which can sometimes lead to amputation of an extremity. And then, of course, having a first-degree family member, since this is an inherited condition, can also lead to the diagnosis of NF-1.
Melanie: So what’s the general prognosis? What do you generally tell other pediatricians about what they can expect with NF-1?
Dr. Morris: Sure. NF-1 is a very unpredictable disorder. The symptoms vary widely from one person to another and can even differ between two people in the same family who actually share the exact same gene mutation. Some people are only very mildly affected with only skin changes, such as the darkly pigmented birthmarks, the café au lait spots, freckling, and only a few neurofibromas, while some patients have major medical problems such as vision loss, epilepsy, and cancer-related to NF-1. Right now it’s actually very difficult to predict how severely affected a newly diagnosed child with NF-1 will be. For this reason, it’s important for children with NF-1 to be seen regularly by an NF-1 specialist who can monitor for new signs and complications of NF-1.
There’s no cure for NF-1, and currently, all the treatment for NF-1 is reactive such that if an NF-1-related complication arises, such as vision loss, scoliosis, painful or disfiguring neurofibromas, or concerns for cancer, patients are typically referred to the appropriate specialist who are experiencing caring for individuals with NF-1.
In addition to the physical manifestations of NF-1, children can also show signs of academic difficulty, ADHD, autism, and other developmental delays. These children are typically referred for formal neuropsychological testing and are treated appropriately with the initiation of individualized education plans at schools, treatment with certain medications, or referral for specific therapy services to improve their academic and long-term success.
Melanie: When would you like to have pediatricians refer to a specialist such as yourself?
Dr. Morris: Yeah, that’s a great question. Café au lait spots are actually very common in the general population with nearly 10% of people having one to two café au lait spots, however if a child is identified as having three or more café au lait spots, they really should be referred to see a doctor who specializes in diagnosing and caring for people with NF-1. If a child has any other feature associated with NF-1 regardless of the number of birthmarks, they should similarly be referred.
Melanie: And you spoke just a bit about treatments. What are some other standard therapies that you might use for a child with NF-1?
Dr. Morris: Yeah, that’s a good question. Right now, the therapies that we use to treat children with NF-1 are actually quite limited. For children who have neurofibromas that are disfiguring or uncomfortable, we typically will refer them to plastic surgeons who are experienced in removing the tumors. Children who have very large plexiform neurofibromas that cause bony problems, such as unequal leg lengths or scoliosis will often be referred to Orthopedic Surgeons so that they can have surgical procedures to improve the stability of their bones and correct the underlining bony deformity. Children who have optic pathway tumors – these are the tumors that grow on the nerve that connects the eye to the brain – sometimes require chemotherapy to treat the underlying tumor that may affect vision.
There are several clinical trials that are currently ongoing looking at different therapeutic agents that could address some of the complications of NF-1. However, they’re not currently clinically available and are only available for eligible patients.
Melanie: And you mentioned a bit about this before, but I’d like you to expand a little bit on how the patient is affected in the long-term, and you mentioned autism, ADHD, ADD, so what do you want other Pediatrician – and even parents to know about what they can expect, or what they can look for, or red flags as the child grows?
Dr. Morris: Sure. The most common long-term problems associated with NF-1 are really physical disfigurement related to the growth of tumors over time and cognitive-behavioral problems including learning disabilities, ADHD, and autism, which can lead to school failure and problems with maintaining friendships and personal relationships. Other severe symptoms or complications related to NF-1 that can affect a patient in the long-term include mood disorders, such as anxiety and depression, sleep problems, chronic pain, and even early death related to increased risk for cancer later in life.
The things that parents and Pediatricians should really be looking for are problems with academic success. Children who tend to do well in Kindergarten and first grade, sometimes will drop off the curve around second or third grade and start to have greater difficulties in school. Problems with initiating and maintaining friendships can sometimes be a red flag. Any child who has a tumor who all of a sudden develops, weakness in that extremity, significant pain associated with that tumor, or changes to the texture or color of the tumor should be immediately referred for evaluation of development into cancer.
Melanie: So wrap it up for us, Dr. Morris. Give Pediatricians your best advice about recognizing NF-1 and tell us about your team. Why is St. Louis Children’s Hospital so great to work with?
Dr. Morris: Sure. Pediatricians really should be looking at all infants who come through their door for any characteristic birthmarks. If they see a child that has three or more birthmarks – these are darkly-colored birthmarks that can range in color from light to very dark brown – they should think of NF-1 as a possible diagnosis. We are always happy to see kids in evaluation in infancy through early adulthood for evaluation of these birthmarks. It’s certainly possible that we won’t be able to secure the diagnosis of NF-1 right away if they have just a few birthmarks. However, we will continue to follow that child every year for every year to make sure that they don’t develop a second symptom suggestive of the diagnosis of NF-1.
We also now have clinical genetic testing available, and so if a parent or Pediatrician is particularly concerned about the diagnosis, we’re able to send blood to be tested for specific NF-1 mutations, which could also confirm the diagnosis. Additionally, if there are any other children who develop unusual features, such as an optic pathway glioma, freckling under their arms or their groin, or if they have unusual bowing of their legs or very progressive scoliosis – and maybe they only have a couple of birthmarks, these are also kids that Pediatricians should be thinking about as having possible diagnosis of NF-1 and should refer them for evaluation.
We have a fantastic comprehensive NF-1 clinic here at the Washington University School of Medicine. We have myself as well as a Neurologist, Dr. David Gutmann, who is the Director of the NF Clinical Program. We also have dedicated Physical Therapists, speech therapists, orthotists, as well as clinical research assistants who help us both with clinical care as well as with clinical and basic research dedicated to treating those with NF-1.
Melanie: Thank you, so much, Dr. Morris for being with us today. A physician can refer a patient by calling Children’s Direct Physician Access Line at 1-800-678-HELP, that’s 1-800-678-4357. You’re listening to Radio Rounds with St. Louis Children’s Hospital. For more information on resources available at St. Louis Children’s Hospital, you can go to StLouisChildrens.org, that’s StLouisChildrens.org. This is Melanie Cole. Thanks, so much, for listening.