Neuro-Fibromatosis: A Neuro-Cutaneous Syndrome

The neurofibromatosis is a genetic disorder in which the growth of the cells of nerve tissues are affected. In the last few years, the increased knowledge of science on neurofibromatosis has not just permitted good clinical management also decrease complication morbidity, resulting in the quality of life of neurofibromatosis patients has improved. In most cases, oncology, neurology, clinical geneticists and dermatology specialists are capable to create the differential prognosis between neurofibromatosis and other diseases and to determine NF complications. However, neurofibromatosis specialists are required for proper NF treatment and genetic analysis because of its variability in the progressive course, phenotype expression, and the involvement of various organs (Rodrigues, L. O. C. et al., 2014).

1.    INTRODUCTION:

The neurofibromatosis (NF) is a genetic disorder of the nervous system. Neurofibromatosis is a cause of tumours formation on the neural tissue wherever in the body. These tumours are commonly non-cancerous but occasionally can become malignant.  These can be developed anywhere in the nervous system, comprising spinal cord, nerves, and brain. This disease usually detected in early adulthood or childhood (Ghalayani, P. et al., 2012).

2.    TYPES OF NEUROFIBROMATOSIS:

Neurofibromatosis has three types and each type with dissimilar signs and symptoms, namely,

1. Neurofibromatosis 1 (NF1)
2. Neurofibromatosis 2 (NF2)
3. Schwannomatosis

2.1      Neurofibromatosis 1 (NF1):

Neurofibromatosis 1 is also known as “von Recklinghausen’s disease”. Neurofibromatosis 1 (NF1) is an autosomal dominant disorder. The Neurofibromatosis 1 gene is placed on chromosomes no 17. Neurofibromin is a product protein that leads to cell growth or tumour suppressor. The neurofibromin mutation or dysfunction on chromosome 17 causes the tumour formation by abnormal growth of cells (Ferner, R. E., 2006).

Sign and Symptoms:

• Light brown spots on the skin. The harmless spots appear in many people. Cafe au lait spots more than six is a strong sign of neurofibromatosis 1. These spots are appearing at birth or during the age first.
• Freckling in the groin area or armpits. Freckling commonly appears between in the ages of 3 - 5. It is smaller than spots of cafe au lait and tends to happen in clusters in the skin layer.
• Pea-sized bumps under or on the skin. These benign tumours are commonly developed under or on the skin. Occasionally, growth would involve various nerves (Mayoclinic staff, 2020).
• Small bumps on the Lisch nodules. Another symptom of neurofibromatosis 1 is the appearance of very small, elevated brown spots or tumour on the lisch nodules. (Ferner, R. E. 2006).

Complications:

Neurofibromatosis complications are varying; even the same family members with NF1 have different complications. Complications of neurofibromatosis 1 include:

• The most common neurological difficulties that are associated with neurofibromatosis 1 is learning and thinking (Ferner, R. E., 2006).
• Rare complications include epilepsy (CNS disorder) and excess fluid buildup in the brain.
• Increased risk of hypertension and may develop abnormalities in the blood vessel.
• People with neurofibromatosis 1 have a high risk of developing other forms of cancer, such as leukaemia, breast cancer, colorectal cancer, tissue cancer, and brain tumours (Mayoclinic staff, 2020).

Treatment:

Treatment for NF1 depends on the sign and symptoms that a patient has:

• Surgery
• Drug therapy under clinical investigation
• Chemotherapy
• Radiation therapy
• Behavioural therapy
• KOSELUGO is an FDA- proved drug indicated for treatment of pediatric patients two years of age or older with NF1(Koselugo , 2020).

2.2      Neurofibromatosis 2 (NF 2):

NF 2 is also called as multiple inherited schwannomas, meningiomas, and ependymomas syndrome (MISME syndrome). NF 2 is an often destructive autosomal dominant disease. It is characterized by the growth of multiple meningiomas and schwannomas. People with NF2 unavoidably develop schwannomas, usually disturbing vestibular nerves and leading to deafness and hearing loss. The neurofibromatosis 2 gene is located on chromosome no 22. Merlin or schwannomin is a protein product, which leads to suppresses tumours. The muted neurofibromatosis 2 gene causes the dysfunction of merlin, leading to abnormal growth of cells (Evans, D. G. R., 2009).

Sign and Symptoms:

The symptoms of NF 2 usually appeared in the early twenties. Including,

• Rare symptoms: nausea, vomiting or true vertigo, except in late-stage disease.
• Early symptoms of NF2. Vestibular schwannomas are loss of hearing, buzzing in the ears.
• Central nervous system: Tumors of the CNS may also develop, and can include meningiomas, low-grade gliomas, neurofibromas, and schwannomas.
• Café-au-lait. On the skin brown or flat spots appear with NF2 patients (Evans, D. G. R., 2009).

Complications:

Complications of Neurofibromatosis 2 include:

• Incomplete or complete deafness
• Damage of facial nerve
• Visualization complication
• Minor benign skin tumours
• Weakness in the extremities
• Multiple benign spinal tumours or brain tumours (Mayoclinic staff, 2020).

Treatment:

There is presently no cure for Neurofibromatosis 2. Patient with NF2 needs regular monitoring to check and to treatment arrangement if required.

• Surgery can be used for tumour removal.
• Symptomatic and supportive treatment.
• Radiation therapy (Evans, D. G. R., 2009).

2.3      Schwannomatosis:

Schwannomatosis is a rare disorder that commonly affects individuals after the age of 20. It is characterized by the incidence of multiple schwannomas and meningiomas. It causes tumours to grow on the spinal, cranial, and peripheral nerves but infrequently on the nerve that conveys balance or sound data from the inner ear to the brain (Kehrer-Sawatzki, H. 2016).

Sign and Symptoms:

• The common symptom of Schwannomatosis is chronic pain, that can occur everywhere in the body
• Weakness or Numbness happen in several parts of the body
• Muscles are damaged (Kehrer-Sawatzki, H. 2016).

Complications:

• The pain that is caused by schwannomatosis disease could be debilitating and can need of any surgical treatment (Mayoclinic staff, 2020).

Treatment:

The schwannomatosis treatment may or may not need surgery, depends on the sign and symptoms that a patient has:

• Non-Surgical treatment for schwannomatosis patients. This includes periodic imaging, pain management, and observation. Patients whose tumours cannot be removed by surgery are therefore recommended for pain management and observation.
• Surgical treatment options for schwannomatosis patients. Surgical treatment may be suggested for tumours of the peripheral nerve associated with schwannomatosis (Schwannomatosis, 2015).

By: Sadia Israr

REFERENCES:

1. Rodrigues, L. O. C., Batista, P. B., Goloni-Bertollo, E. M., Souza-Costa, D. de, Eliam, L., Eliam, M. Vidigal, P. V. T. (2014). Neurofibromatoses: part 1-diagnosis and differential diagnosis. Arquivos de Neuro-Psiquiatria, 72(3), 241–250.
2. Ghalayani, P., Saberi, Z., and Sardari. F. (2012). Neurofibromatosis type I (von Recklinghausen's disease): A family case report and literature review. Dental Research Journal. 9(4): 483–488.
3. Ferner, R. E. (2006). Neurofibromatosis 1. European Journal of Human Genetics, 15(2), 131–138.
4. Mayoclinic staff. (2020, April 08). Neurofibromatosis. Retrieved from https://www.mayoclinic.org/diseases-conditions/neurofibromatosis/symptoms-causes/syc-20350490?p=1
5. Astra Zeneca Pharmaceuticals LP. Koselugo (Selumetinib). (June 21, 2020). U.S. Food and Drug Administration. Retrieved from. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213756s000lbl.pdf
6. Evans, D. G. R. (2009). Neurofibromatosis Type 2 (NF2): A clinical and molecular review. Orphanet Journal of Rare Diseases, 4(1), 16.
7. Kehrer-Sawatzki, H., Farschtschi, S., Mautner, V.-F., & Cooper, D. N. (2016). The molecular pathogenesis of schwannomatosis, a paradigm for the co-involvement of multiple tumour suppressor genes in tumorigenesis. Human Genetics, 136(2), 129–148.
8. Schwannomatosis. National Institute of Neurological Disorders and Stroke. February 2015; https://rarediseases.info.nih.gov/diseases/4768/schwannomatosis.