Along with other proteins, Neurofibromin protein (NP) is located in Chromosome 17. Neurofibromin protein will be a regulator, inhibitor, suppressor of cell growth and other functions in the human body system.
The mutated genes of Chromosome number 17 leads to loss of neurofibromin protein, resulting to uncontrolled cell growth.
Mutation of genes means a permanent alteration in the DNA sequence that makes up a gene.
Neurofibromin protein has so much functions in our system such as:
* It binds RAS in the MAP Kinase pathways - Neurofibromin protein binds RAS and inhibits or slow down the process.
If you are wondering what MAP kinase is? It's a cell growth pathway. On normal senario, If you inhibit or slow down MAP kinase pathway by biding RAS it will stop cell growth
In the case of Neurofibromatosis type 1. This tumor suppressor neurofibromin protein is not working. The cell growth is not regulated.
*Patient might have some difficulty in learning due to protein kinase pathway affectation, which functions as a cell cycle progression linked to learning and memory.
* Neurofibromin also interacts with many other proteins that are engaged in intracellular transport.
The fact that *neurofibromin is engaged in many cellular processes, has significant consequences when the proper protein functioning is impaired, due to decreased protein level or activity. It affects the normal cell function and results in disturbances of organism development, that leads to the occurrence of clinical signs specific for NF1.
Neurofibromin Protein (NP) binds RAS to the Kinase Pathway to slow down process of cell growth, regulates, inhibits certain functions.
In the case of NF1 or Neurofobromatosis type 1, Neurofibromin protein is not working.
Cafe au lait spots ( coffee with milk like/ brown birth marks ) - Having 6 or more cafe au lait spots is a strong indicator of NF1. They are usually present at birth or appear during the first years of life and then stabilize. Freckling in the armpits or groin area. Freckling usually appears by ages 3 to 5. There are studies that it's the mutation of the gene that caused the freckling and number of brown birth marks.
(+ 2 or more cutaneous/subcutaneous neurofibromas or one plexiform neurofibroma)
Lisch Nodules - Pigmented iris hemartomas ( excess at least 2 pigment gathered on the iris ) or inside the colored portion of the eyes. An excess pigment tumors, these harmless nodules can't easily be seen and don't affect your vision. Assessment are done by slit lamp examination
Cutaneous Neurofibromas - bumps/peduncular tumors or multiple soft tumors growing on the patients body. They are tumors of the nerve cells or nerve sheet tumors ( an excess production of myelin sheet ). Inside the myelin sheet there are fibroblast tissues (Tumors diagnose by biopsy ). Furthermore, biopsy of asymptomatic cutaneous neurofibromas should not be undertaken for diagnostic purposes in individuals with clearcut NF1.
*Usually the first method of diagnosis is checking for the number of brown birth marks > then Lisch Nodules > the kind of tumor or cuntaneous neurofibromas related to it.
Increased susceptibility to tumor formations
Optic Gliomas - Tumors of the optic nerves resulting to deficits in vision. These tumors usually appear by age 3, rarely in late childhood and adolescence and almost never in adults.
Neurological deficits - Affectation of a nerve, spinal cord or brain function in a specific location. Ex. left or right arm, some parts of the tongue, vision and hearing problems ( considered as focal neurological deficits ).
Skeletal defects or bone deformities - Ex. Abnormal bone growth and a deficiency in bone mineral density can cause bone deformities such as a curved spine (scoliosis) or bowed lower leg, bony dysplasia (sphenoid wing dysplasia, bowing of long bone ± pseudarthrosis).
A first degree relative of also have NF1
Patient's with NF1 may also manifest some of this characteristics:
Learning disabilities - Due to protein kinase pathway affectations, which regulates cell cycle progression or learning and memory formation processes. Impaired thinking skills are common in children with NF1, but are usually mild. Often there is a specific learning disability, such as problem with reading or mathematics. Attention-deficit/hyperactivity disorder (ADHD) is also common.
Speech disorders - In some cases there are articulation difficulties, hearing impairment, abnormalities in loudness, and stuttering. Delays in speech and articulation development have been found in school-aged children and adolescents with neurofibromatosis type 1 (NF1).
Neurocutaneous-skeletal disorder often accompanied with varying degrees of cognitive and motor problems that potentially affect speech and language.
Larger than average head size - Children with NF1 tend to have a larger than average head size due to increased brain volume.
Short stature - Children with NF1 maybe at risk for short stature with growth hormone deficiency (GDH). There are cases of NF1 children with below average in height due suprasellar lesions (pituitary ).
Pheochromocytomas - Tumors in the adrenal glands resulting to excess production of norephineprine. The patient might be hyperactive or excitable.
Hypertension - NF1 patients with a stenosis of the renal artery, phaeochromocytoma or in cases of several cervical neurofibromas.
Cardiovascular monitoring♡ and blood pressure monitoring to detect heart problems/ blood pressure abnormalities or anything associated with it and to prevent more possible risk of complications, must be practice by patients with NF1.♡
*Treatment of Neurofibromatosis:
The mainstay of management is age specific monitoring and assessment for signs and symptoms of secondary disease related to NF, prevention of further progression and complications of NF and patients education.
The goal in NF is promote healthy growth and development. It was found out the undernourished cells can make abnormal genes more aggressive.
Monitoring and prevention of complications, managing symptoms as soon as it manifest.
NF might cause large tumors that might create discomfort and pressure in the nerve, then surgery can help alleviate the suffering.
Some people may benefit from other therapies, such as stereotactic radiosurgery or medications to control pain.
Timely diagnosis - specially to children who develops signs of NF. Although tumors are benign and slow growing.
Plastic surgery and laser therapy may be used to remove lesions on the surface of the skin and help improve appearance.
*Note: Complications comes when the tumors deformed or malformed nerve tissues or compressing organs in the body.
*Other infomations about Neurofibromatosis:
Autosomal dominant disorder : In an autosomal dominant disorder, the person inherited the abnormal gene from only one parent ( one parent is a carrier of NF1 gene ). Often one of the parent may also have the disease.
In some cases it is a genetic mutation and in the half of cases these are inherited from a person's parents.
Both NF1 and NF2 are nerve sheet tumors.
It's a Neurocutaneous disorder - which means more involve nerve cells and skin.
Development of cancer in NF1 patients is about 3 to 7% it happens when a benign or non canceous neurofibroma turns in to a cancerous form called sarcoma.
Prepared by:
Jade Chen JAMDC
No comments:
Post a Comment