Neuroblastoma actually press against it resulting in numbness,

Neuroblastoma is an extracranial cancer that typically affects children and occurs when immature nerve cells or ‘neuroblasts’ become abnormal and proliferate uncontrollably, creating a tumour. Characteristically, the tumours point of origin is above the kidney’s, in the nerve tissues of the adrenal gland. However, tumours can also form in the nerve tissue of areas including the abdomen, pelvis, chest or neck.

Additionally, neuroblastoma’s if left untreated can metastasise to other areas of the body such as the liver, skin, or bones. Patients typically express general signs and symptoms when suffering from neuroblastoma such as tiredness (fatigue), irritability, fever, loss of appetite, weight loss, pain, or diarrhea. However more specific signs and symptoms are determined by the site of the tumour and where it may have spread. For example, abdomen tumours can result in abdominal swelling, a tumour in the chest may hinder breathing, neck tumours can cause nerve damage leading to Horner syndrome, which precedes signs and symptoms including small pupils, drooping eyelids, red skin and decreased sweating.

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Metastasis resulting in the spread of the tumour to the bone can result in bruises, bone pain, dark circles around the eyes or pale skin. Tumours in the backbone can apply pressure to the spinal cord and actually press against it resulting in numbness, weakness or paralysis in the arms and legs. Lastly, a rash of bluish and or purplish bumps that look like blueberries indicates the spread of the neuroblastoma to the skin. Furthermore, these cancers can often release hormones that result in various other symptoms and signs such as rapid heartbeats, high blood pressure, sweating and flushing of the skin.

In some very rare cases of neuroblastoma, individuals may develop opsoclonus myoclonus syndrome, which causes muscle spasm like movements in the eyes and muscles, due to the immune system malfunctioning and attacking nerve tissue. In infants, the most common cancer is neuroblastoma which affects approximately 1 in 100,000 children whom are often younger than 1 year. The cause of neuroblastoma is similar to that of other cancers where an accumulation of genetic mutations, particularly in critical genes results in the abnormal and uncontrollable growth and division of cells which ultimately leads to the formation of a tumorous growth. Critical genes are genes that control cell growth, proliferation and differentiation and typically mutations in these genes are attained during a person’s lifetime and are known as somatic mutations. Somatic mutations are only ever present in particular cells and cannot be inherited, neuroblastoma that is caused by these somatic mutations is called the sporadic form of this condition. It is believed that in order to cause sporadic neuroblastoma at least two somatic gene mutations are required to cause the condition. Furthermore, familial neuroblastoma is when gene mutations that are responsible for the development of the cancer are inherited from a parent. This condition is very rare however with about 1 to 2 percent of affected individuals develop the condition through inheritance.

Familial neuroblastoma has an autosomal dominant inheritance pattern, this means that the chances of developing the disorder is increased for every copy of the altered gene in each cell. However, the inheritance is thought to have incomplete penetrance as not all individuals who receive the altered gene from a mother or father actually develop neuroblastoma. Possessing the mutated gene predisposes an individual to develop the condition, however it is thought that an additionally somatic mutation is needed to cause neuroblastoma. Many genes are likely involved in the development of the cancer. In particular, mutations in the genes ALK and PHOX2B have shown to increase the risk of developing the condition.

Mutations of the ALK gene result in an abnormal version of a protein known as ALK receptor tyrosine kinase which results in the protein becoming constitutively activated leading to increased cell proliferation of immature nerve cells and hence the development of neuroblastoma. Similarly, mutations in PHOX2B gene are believed to interfere with the promotion of nerve cell differentiation which is typically performed by the PHOX2B protein. As a result, the disruption of differentiation caused by this mutation leads to an excess of immature nerve cells which ultimately leads to the development of neuroblastoma. Furthermore, genetic changes associated with the oncogene MYCN have been known to be related to the severity of the condition but not thought to cause it. Roughly one quarter of people with neuroblastoma have an amplification of the MYCN gene, this phenomenon is called gene amplification. Patients who are affected by MYCN amplification tend to have rapid tumour development and poor prognosis regardless of whether or not other favourable factors are at play.

Typically, the age distribution of patients with neuroblastoma is as follows: 40% of patients are less than 1 year of age when diagnosed, 35% are between 1-2 years and 25% are older than 2 years when the condition is identified. Incidences tend to decrease each consecutive year up to age 10 at which point the disease is very rare, with males having a slightly higher incidence of the condition than females with a male to female ratio of 1.2:1.


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