About von recklinghausen's disease

What is von recklinghausen's disease?

Neurofibromatosis type 1 (NF1), also called von Recklinghausen's disease, is a rare genetic disorder characterized by the development of multiple noncancerous (benign) tumors of nerves and skin (neurofibromas) and areas of abnormally decreased or increased coloration (hypo- or hyperpigmentation) of the skin. Areas of abnormal pigmentation typically include pale tan or light brown discolorations (cafe-au-lait spots) on the skin of the trunk and other regions as well as freckling, particularly under the arms (axillary) and in the groin (inguinal) area. Such abnormalities of skin pigmentation are often evident by one year of age and tend to increase in size and number over time.

At birth or early childhood, affected individuals may have relatively large benign tumors that consist of bundles of nerves (plexiform neurofibromas). Individuals with NF1 may also develop benign tumor-like nodules of the colored regions of the eyes (Lisch nodules) or tumors of the optic nerves (second cranial nerves), which transmit nerve impulses from the innermost, nerve-rich membrane of the eyes (retinas) to the brain. More rarely, affected individuals may develop certain malignant (cancerous) tumors.

NF1 may also be characterized by unusual largeness of the head (macrocephaly) and relatively short stature. Additional abnormalities may also be present, such as episodes of uncontrolled electrical activity in the brain (seizures); learning disabilities; speech difficulties; abnormally increased activity (hyperactivity); and skeletal malformations, including progressive curvature of the spine (scoliosis), bowing of the lower legs, and improper development of certain bones. In individuals with NF1, associated symptoms and findings may vary greatly in range and severity from case to case. Most people with NF1 have normal intelligence but learning disabilities appear in about 50% of children with NF1.

NF1 is caused by changes (mutations) of a relatively large gene on the long arm (q) of chromosome 17 (17q11.2). The gene regulates the production of a protein known as neurofibromin, which is thought to function as a tumor suppressor. In about 50 percent of individuals with NF1, the disorder results from spontaneous (sporadic) mutations of the gene that occur for unknown reasons. In others with the disorder, NF1 is inherited as an autosomal dominant trait.

The name "neurofibromatosis" is sometimes used generally to describe NF1 as well as a second, distinct form of NF known as neurofibromatosis Type II (NF2). Also an autosomal dominant disorder, NF2 is primarily characterized by benign tumors of both acoustic nerves, leading to progressive hearing loss. The auditory nerves (eight cranial nerves) transmit nerve impulses from the inner ear to the brain.

What are the symptoms for von recklinghausen's disease?

VRD affects the skin and the peripheral nervous system. The first symptoms usually appear in childhood and affect the skin.

Symptoms of VRD affecting the skin include the following:

  • Café au lait macules are tan spots in different sizes and shapes. They can be found in multiple places on the skin.
  • Freckles can occur under the arms or in the groin area.
  • Neurofibromas are tumors around or on peripheral nerves.
  • Plexiform neurofibromas are tumors affecting the nerve bundles.

Other signs and symptoms of VRD include the following

  • Lisch nodules are growths affecting the iris of the eyes.
  • Pheochromocytoma is a tumor of the adrenal gland. Ten percent of these tumors are cancerous.
  • Liver enlargement can occur.
  • Glioma is a tumor of the optic nerve.

Bone involvement from VRD includes short stature, deformities of bones, and scoliosis, or abnormal curvature, of the spine.

What are the causes for von recklinghausen's disease?

The cause of VRD is a genetic mutation. Mutations are changes in your genes. The genes make up your DNA, which defines every physical aspect of your body. In VRD, a mutation occurs on the neurofibromin gene, causing an increase in the development of cancerous and noncancerous tumors.

While most cases of VRD are the result of a genetic mutation in the neurofibromin gene, there are also acquired cases due to spontaneous mutations. The Journal of Medical Genetics notes that in about half of all cases, the mutation appears spontaneously. This means no family member has the illness, and it’s not inherited. The acquired disease can then pass forward to future generations.

What are the treatments for von recklinghausen's disease?

VRD is a complex illness. Treatment must address many different organ systems within the body. Childhood exams should look for signs of abnormal development. Adults require regular screening for cancer caused by the tumors.

Treatment in childhood includes:

  • evaluation for learning disabilities
  • evaluation for attention-deficit hyperactivity disorder (ADHD)
  • orthopedic evaluation to treat scoliosis or other treatable bone deformities

All patients should have yearly neurological exams and yearly eye exams.

Tumors can be treated by several methods, including:

  • laparoscopic removal of cancerous tumors
  • surgery for removal of tumors affecting the nerves
  • radiation therapy
  • chemotherapy

What are the risk factors for von recklinghausen's disease?

Tumors develop on nerve tissue as a result of a series of hereditary diseases called von recklinghausen's disease. Anywhere in the neurological system, including the brain, spinal cord, and nerves, these tumors can form. Von recklinghausen's disease comes in three different forms: schwannomatosis, neurofibromatosis 1 (NF1), and neurofibromatosis 2 (NF2). While NF2 and schwannomatosis are typically detected in early adulthood, NF1 is typically diagnosed in childhood.

Risk factors of von recklinghausen's disease
These are the risk factors -

1. A family history of von recklinghausen's disease is the main risk factor for the condition. About half of those with NF1 and NF2 received the condition from a parent who had it. People with NF1 and NF2 who do not have affected relatives are more likely to have a novel gene mutation.

2. Both NF1 and NF2 are autosomal dominant diseases, which means that there is a 50% probability that the genetic mutation will be passed down to any offspring of an affected parent.

3. It is unclear how von recklinghausen's disease is inherited. According to current research, there is a 15% chance of inheriting schwannomatosis from a parent who has the condition

Management of the von recklinghausen's disease

For the management of the condition, routine monitoring is crucial. All patients are advised to have annual physical exams, as well as regular eye tests and blood pressure checks. Annual ophthalmologic examinations, routine measurements of head circumference, and developmental evaluations are all advised for kids with NF1. Depending on the location and symptoms, advanced imaging (MRI, PET, or PET/CT) may be indicated to monitor internal tumors. The use of whole-body MRI as a technique for tracking internal cancers is being researched. For females with NF1, annual breast cancer screening (either by mammography or breast MRI) is advised to start at age 30.

Six or more café-au-lait spots of at least 5 millimeters [mm] in size (before puberty) or 15 mm in size (after puberty),Freckling in the underarms (axillary) or groin (inguinal) regions,Two or more neurofibromas of any type or one plexiform neurofibroma,Optic pathway glioma
Increased risk of developing noncancerous (benign) and cancerous (malignant) tumors
Neurontin, Gralise, Horizant) or pregabalin (Lyrica),Tricyclic antidepressants such as amitriptyline

Is there a cure/medications for von recklinghausen's disease?

VRD increases your risk for cancer. You should have tumors checked regularly by your doctor. They will look for any changes that indicate cancer. Early diagnosis of cancer leads to a better chance for remission.

People with VRD may have large tumors on the body. Removal of visible tumors on the skin can help with self-esteem.

VRD is a genetic disease. If you have VRD, you can pass it to your children. You should visit a genetic counselor before having children. A genetic counselor can explain the odds of your child inheriting the disease.

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