Unlike the other types of brain tumours that I mentioned in the section Introduction to Brain Tumours which are induced by random mutations in genes because of exposure to mutagens, there are certain types of brain tumours that can be passed on from generation to generation because of the loss of tumour suppressor genes. These disorders are all autosomal dominant, and there are four well-known types of familial tumour syndromes, and in the past they were labelled as ‘neurophakomatoses’ because they manifested both within the nervous system and the cutaneous (skin) system. These syndromes are known as neurofibromatosis (types 1 and 2), tuberous sclerosis and von Hippel-Lindau disease. The symptoms associated with these conditions, like other brain tumours, are dependent on where in the brain the tumours are located.
What are the similarities and the differences between type 1 and
type 2 neurofibromatosis?
Neurofibromatosis is well-known for the presence of neurofibromas, which as the picture alongside demonstrates, are harmless lumps that grow anywhere on the surface on the skin. There are two types: solitary (which is self-explanatory) and plexiform neurofibromas, which can cause alterations in appearance due to the bundling effect. Type 1 NF is much more common than type 2 NF, however in type 1, there may or may not be a link between the genetic mutation and the disease, however there is always some degree of correlation in type 2 NF. I’ll discuss each of them briefly below.
Type 1 Neurofibromatosis
Type 1 neurofibromatosis is characterised by tumours in and around the eye and the skin area. There are several types of tumours associated with this condition, including gliomas of the optic nerve and neurofibromas. Also, there are unique diagnostic features associated with this disease, known as Lisch nodules and cafe au lait spots: these features are seen in the iris and macula of the eye, respectively. People that develop neurofibromas have a higher risk of developing malignant tumours than the normal population. Like I mentioned earlier, despite the fact that someone may have the NF1 genetic mutation, they may through life asymptomatically, whereas others may go through progressive deterioration with compression of the spinal cord, disfiguring lesions and other spinal deformities.
Type 2 Neurofibromatosis
Type 2 neurofibromatosis is characterized by tumours within the meninges (meningiomas) and tumours within the ear canal, otherwise known as bilateral vestibular or acoustic schwannomas. Additionally, there be ependymomas present within the spinal cord, as well as non-neoplastic lesions within the neurons composed of inappropriately placed glial or Schwann cells.
Tuberous sclerosis is a condition which results from mutations within the TSC-1 and TSC-2 genes. TSC-1 is the gene which encodes hamartin and TSC-2 encodes tuberin. They are both tumour-suppressing genes, and their proteins are involved in the rate of cellular division and protein synthesis within neurons. When these genes are mutated benign tumours and hamartomas (non-tumour structures resulting from faulty organ development) grows within the brain and other tissues. A table outlining the different types of abnormalities that develop is seen below:
Von Hippel-Lindau Disease
Von Hippel-Lindau disease is characterized by a mutation of the VHL gene: the protein controls the process of angiogenesis (blood vessel expansion). Like the previous types of tumours, it is autosomal dominant, and the patient may either develop cysts or haemoangioblastomas. The location of these abnormalities are discussed in the table below. The treatment for von Hippel-Lindau disease is targeted at the neoplasms which cause the symptoms, and it may include surgical resection and laser therapy in the case of haemoangioblastomas within the retinas.