Genetic Brain Disorders: Causes and Four Examples

A genetic brain disorder is caused by a variation or a mutation in a gene. A variation is a different form of a gene; a mutation is a change in one. These disorders affect how the brain develops and how it works.

How they arise

• Random mutations, or mutations caused by something in the environment, such as cigarette smoke.
• Inheritance — a mutated gene, or a group of genes, passed down through a family.
• A combination of genetic changes and other outside factors.

Many people with a genetic brain disorder do not make enough of certain proteins that shape how the brain develops and functions. The disorders can cause serious problems in the nervous system. Some have treatments that control the symptoms; some are life-threatening.

Four examples

Leukodystrophies are a group of rare genetic disorders of the central nervous system — the brain and spinal cord. They damage its white matter: the nerve fibres (axons) that connect nerve cells, and myelin, the layer of proteins and fats that covers and protects those fibres and speeds signals between cells. Damaged white matter slows or blocks signals, causing trouble with movement, vision, hearing and thinking. There are over 50 types. Some are present at birth, others appear in toddlers, and a few mainly affect adults; most get worse over time.

Phenylketonuria (PKU) is an inherited disorder that raises the level of phenylalanine, an amino acid found in foods such as meat, eggs, nuts and milk and in some artificial sweeteners. Untreated, it can build up to harmful levels and cause intellectual disability and other serious problems. Babies with the most severe form, classic PKU, seem well for the first few months. PKU can often be managed with a diet low in phenylalanine; people with very mild forms may need no treatment.

Tay-Sachs disease is a rare inherited disorder in which nerve cells in the brain and spinal cord die. In its most common, infantile form, babies develop normally until 3 to 6 months of age, then slow down, weaken and lose skills such as turning over, sitting and crawling; they later have seizures, trouble swallowing, vision and hearing loss and intellectual disability, and usually live only into early childhood. Juvenile and late-onset forms are rare and usually milder.

Wilson disease is an inherited disorder in which too much copper builds up in the body, especially in the liver, brain and eyes. Signs usually first appear between the ages of 6 and 45, most often in the teenage years, and combine liver disease with neurological and psychiatric problems — among them clumsiness, tremors, trouble walking and speaking, depression, anxiety and mood swings. In many people, copper forms a green-to-brownish ring, the Kayser-Fleischer ring, around the coloured part of the eye.

Sources

• MedlinePlus, U.S. National Library of Medicine, "Genetic Brain Disorders." https://medlineplus.gov/geneticbraindisorders.html
• The four examples draw on MedlinePlus's own pages: "Leukodystrophies" (https://medlineplus.gov/leukodystrophies.html) and MedlinePlus Genetics on phenylketonuria, Tay-Sachs disease and Wilson disease (https://medlineplus.gov/genetics/).
• Rewritten in hubnx's own words.