Epigenetics
The classical view of cancer is a set of diseases driven by progressive genetic abnormalities that include mutations in tumor-suppressor genes and oncogenes, and in chromosomal abnormalities. A role for epigenetic alterations was identified in the early 21st century.Epigenetic alterations are functionally relevant modifications to the genome that do not change the nucleotide sequence. Examples of such modifications are changes in DNA methylation (hypermethylation and hypomethylation), histone modification and changes in chromosomal architecture (caused by inappropriate expression of proteins such as HMGA2 or HMGA1). Each of these alterations regulates gene expression without altering the underlying DNA sequence. These changes may remain through cell divisions, endure for multiple generations, and can be considered as equivalent to mutations. Epigenetic alterations occur frequently in cancers. As an example, one study listed protein coding genes that were frequently altered in their methylation in association with colon cancer. These included 147 hypermethylated and 27 hypomethylated genes. Of the hypermethylated genes, 10 were hypermethylated in 100% of colon cancers and many others were hypermethylated in more than 50% of colon cancers.While epigenetic alterations are found in cancers, the epigenetic alterations in DNA repair genes, causing reduced expression of DNA repair proteins, may be of particular importance. Such alterations may occur early in progression to cancer and are a possible cause of the genetic instability characteristic of cancers.Reduced expression of DNA repair genes disrupts DNA repair. This is shown in the figure at the 4th level from the top.
Andermann syndrome, also known as agenesis of corpus callosum with neuronopathy (ACCPN) and Charlevoix disease, among other names, is a very rare neurodegenerative genetic disorder that damages the nerves used to control muscles and related to sensation and is often associated with agenesis of the corpus collosum.It was first described by Eva Andermann et al. in 1972. Symptoms and signs
Symptoms begin in infancy and include:
hypotonia
areflexia
amyotrophy
variable degrees of dysgenesis of the corpus callosum
mild to severe intellectual and developmental delay
psychiatric problems including paranoid delusions, depression, hallucinations and autistic-like behavior

Genetics
The inheritance pattern is autosomal recessive. Several genes have been associated with the disorder, including SLC12A6. Neuropathology
Autopsy examination of 8 cases has shown both developmental and degenerative neuropathologic features in this disease, consistent with clinical duality as both a neurodevelopmental and neurodegenerative disorder.In the central nervous system, accompanying the hypotonia at birth is hypoplasia of the corticospinal tracts. Another developmental feature is seen in the corpus callosum, which varies from absent to hypoplastic. The anterior commissure is almost always absent, but occasionally hypoplastic. A bundle of Probst can be found running antero-posterior rather than crossing the midline. The axonal damage due to the channel deficiency can cause a reactive axonal overgrowth leading to small tumor-like growths, or tumorlets, called axonomas, or balls of aberrant axons. Damaged axons can also show a sign of inhibition of axonal transport, forming axonal spheroids.