Neurocutaneous Disorder Series #1: Neurofibromatosis

Neurofibromatosis

Before explanations done on neurofibromatosis, what is neurocutaneous disorder? The neuro stands for nervous system (brain, spinal cord) whereas the cutaneous refers to skin, so basically, it is a disorder of the nervous system and also the skin.

Introduction-Neurofibromatosis is a type of neurocutaneous disorder, a genetic condition that causes tumors to grow on the skin and also along the nerves, but bear in mind that these tumors are benign which mean they are not cancerous. How do people get this particular condition? Well, it is an autosomal dominant disorders, which means, if either one of the parents have neurofibromatosis, there is actually a 50% chance of the children getting it. Among all the cases of neurofibromatosis, some of them are new mutation where they develop spontaneously due to abnormal DNA sequence. There are 2 types of neurofibromatosis, namely Neurofibromatosis Type 1 (NF1) and Neurofibromatosis Type 2 (NF2). Neurofibromatosis Type 1 and Neurofibromatosis Type 2 are caused by 2 different gene mutation, NF1 is located on the Chromosome 16 whereas NF2 is located on the Chromosome 22, Chromosome 1 until Chromosome 22 are known as autosomes.

Example of Neurofibromatosis Image Source

Neurofibromatosis Type 1 (NF1)

Epidemiology- Neurofibromatosis Type 1, affects 1in 4000 live births and among these, 1/3 of them are of new mutation which means it occurred spontaneously without being inherited from the parents.

Diagnostic Criteria-There is a criteria known as the NIH Criteria, is being used to diagnose NF1. The NIH criteria: Clinical presentations based on presence of at least two of the following,

1. Six or more café-au-lait macules over 5 mm in diameter in prepubertal individuals and over 15mm in greatest diameter in postpubertal individuals.
2. Two or more neurofibromas of any type or one plexiform neurofibroma.
3. Freckling in the axillary or inguinal regions.
4. Two or more Lisch nodules (iris hamartomas).
5. Optic glioma.
6. A distinctive osseous lesion such as sphenoid dysplasia or thinning of long bone cortex, with or without pseudarthrosis.
7. First-degree relative (parent, sibling, or offspring) with NF-1 by the above criteria.

Lisch Nodules Image Source

Clinical Presentations- Those who have NF1, they have different symptoms from one another. Some might have similarities but not exactly the same. Some experience it even after birth and some only a decade after that. It really does vary for each individual. Also, inheritance from the parents does not mean that the child will have the exact presentations as the parents, it might be milder or it might be worse in terms of symptoms and also cosmetic concerns, this is largely due to the fact that hormonal changes and disturbances in the body play an important role in the size of the neurofibroma. Clinical presentations such as café-au-lait spots, freckling and Lisch nodules exert minimal or no health risk to a person. Whereas for neurofibromas itself, do pose distress in emotions and appearance as affected person will have a lower self esteem and reluctant to socialize due to such condition. Besides affecting the skin and also the nerves, neurofibromas can grow inside the body that affect the organs and system functioning. About 1/2 of the NF1 affected people have speech difficulties, learning difficulties, seizures and hyperactive. There is less than 1% chance that these tumors will turn to be malignant and thus require treatment.

Cafe Au Lait Spots Image Souce

Neurofibromatosis Type 2

Epidemiology- This is also known as the central neurofibromatosis. Neurofibromatosis Type 2 (NF2) occurred due to gene mutation that occurred in that particular pair of chromosome 22. This NF2 is actually very rare as it affects 1 in 40000 live births.

Clinical Presentations- In a person, there is this one nerve called the acoustic nerve which is also known as the 8th cranial nerve. So, in NF2, tumors will actually grow on the acoustic nerve. Function of this acoustic nerve is for hearing function, thus when tumors grow on it, it will have a pressure effect on the nerve and thus causing hearing disturbances and difficulties, such symptoms include tinnitus, feeling dizzy, facial numbness, balance difficulties and headaches. Besides affecting the nerve, it also affect the spinal cord where there is a spinal cord tumor.

Diagnostic Criteria- How to diagnose NF2?
The diagnostic criteria for NF2 has been established by a consensus of experts. A person is thought to have NF2 if they have a:

1.Confirmed (definite) diagnosis of NF2:
bilateral vestibular schwannomas (may also be known as acoustic neuroma)

1. (Probable) diagnosis of NF2:
   -family history of NF2 AND
   -unilateral vestibular schwannomas or any 2 of the following tumor types: meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity, juvenile cortical cataract

2. A person should be evaluated for NF2 if the conditions below are met:
   -unilateral vestibular schwannoma plus at least 2 of any of the following: meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacities/juvenile cortical cataract
   -2 or more meningiomas plus unilateral vestibular schwannoma or any 2 of the following: glioma, schwannoma, juvenile posterior subcapsular lenticular opacities/juvenile cortical cataract

Management of Neurofibromatosis in general

For those who are eager to know whether there is treatment available for neurofibromatosis, actually no treatments are available. The only thing that can be done is symptomatic management and also continuous monitoring.

Symptomtic treatments /managements - are being done when patients complain of symptoms such as pain, then can give painkiller as some of them might experience scoliosis and abnormal posture causing and elicit pain.

Monitoring - What to monitor?
-Examination of the skin: This is to be done thoroughly and to check for any new neurofibromas and also to check for any -malignant changes.
-Examination of the eyes under a slit lamp to detect any Lisch Nodule
-Bone assessment to check for scoliosis (abnormal curvature of the spine) or any bone fractures that heal poorly
-Blood Pressure
-Physical development: height, weight
-Reading, writing, problem solving and comprehension abilities