Reviewed by John K. Fink, M.D., SPF Medical Advisor

What is an hereditary disorder?

A hereditary (genetic) disorder is caused by a change (mutation) in a gene. Genes are pieces of biochemical information that form the code (instructions) for the thousands of proteins the body uses to build itself and function. Half come from the mother and half come from the father. Some genes are responsible for obvious traits such as eye color. Others control the production of substances essential to bodily processes. Some act as on-off switches for other genes.

When a gene is altered, the correct instructions cannot be coded to make the corresponding protein. As a result, the protein might not be created at all, or might be made incorrectly. While many gene mutations have little or no effect on the body, some can result in the development of serious genetic disorders. In HSP, gene mutations alter the code for proteins involving particular nerve cells in the brain and spinal cord, which disrupts their proper functioning.

The changed (mutant) gene that causes HSP can be passed down from parent to child. However, inheriting a mutant HSP gene does not automatically mean someone will have the disorder. There are many forms of HSP, each caused by different genes. The risk of inheriting the disease depends upon particular features of the gene involved.

In addition to reading over the information below, please check out the new NIH Genetics Home Reference for information about genetics.

Genes and chromosomes

Humans have about 50,000 genes. Genes come in pairs, and each pair makes up a very small section on a chromosome. Humans have 46 chromosomes arranged in 23 pairs in every cell in the body, except for the sperm and egg cells.

Twenty-two of these pairs are called “autosomes” and they are the same for each sex. The twenty-third pair of chromosomes is comprised of the sex chromosomes. Women have two X chromosomes while men have one X and one Y chromosome. The Y-chromosome determines maleness.

Sperm and egg cells contain just one of the chromosomes from each pair, i.e. 23 individual chromosomes. When a sperm and egg come together and conception begins, a new cell is formed that brings the individual chromosomes together into one pair. Thus, every person receives half of their genes from their father (from the sperm cell), and half from their mother (from the egg cell).

Risk of inheritance

HSP is not one individual disorder, but a group of similar disorders, each caused by different genes. The risk of inheriting an HSP disorder depends upon particular features of the gene involved - whether the gene lies on an autosome or the X-chromosome and whether the gene is “dominant” or “recessive”. In some forms of HSP, it can also depend upon the sex of the child and/or the parent. There are three different modes of inheritance: autosomal dominant, autosomal recessive or X-linked.

• Autosomal dominant
  Most forms of HSP are autosomal dominant. “Autosomal” means that the HSP gene is located on one of the autosomal chromosomes. The gene can be present in either sex, and it can be passed down from either a mother or a father to a son or a daughter. “Dominant" means that only one HSP gene is needed to cause the disorder.
  
  Since there is 50% chance a child will receive the dominant HSP gene mutation from the affected parent, there is a 50% chance the child will inherit the gene and the disorder. This is the same risk for every birth, independent of every other birth.
  
  Note: There are many reasons why someone with no apparent family history may have an autosomal dominant form of HSP. Please see “How can it be HSP when no one else in the family has it?” below.
   
• Autosomal recessive
  Some forms of HSP are autosomal recessive. This type of HSP also lies on one of the autosomes, so it can be present in males or females and passed to males or females. Since it is “recessive”, two copies of the gene are needed to result in the disorder – one from each parent.
  
  Neither parent of someone with autosomal HSP has the condition. Instead, they are “carriers”. They each have one mutant HSP gene and one normal (not mutated) HSP gene. A mutant HSP gene that is recessive can be passed down silently for generations until someone finally inherits the recessive gene from both parents and develops the disorder.
  
  If a mother and father are each carriers for a recessive HSP gene mutation, each of their children has a 25% chance of developing HSP. This is the same risk for every birth. There is a 50% risk the child will be a carrier like the parents. That child would receive one mutant HSP gene from one parent and a normal (non-mutated) HSP gene from the other. There is a 25% chance that the child will receive only the normal (not mutant) HSP genes from each parent. This child would be neither affected by HSP, nor be a carrier.
  
  It is unlikely for individuals with autosomal recessive HSP to have children with the disorder because their spouse would have to have the disorder or be a carrier. This is possible in marriages between cousins in families with this type (recessive) of HSP.
   
• X-linked
  Some HSP genes are found on the X-chromosome. Disorders due to genes on the X chromosome are called sex-linked since the gene is on one of the sex chromosomes.
  
  The inheritance risks and severity of this type of HSP differ depending upon the individual’s sex. Women with an X-linked mutant HSP gene are generally not affected by the disorder; or, if they are affected, usually have less severe symptoms than males.
  
  Each son of a woman who is a carrier for X-linked HSP has a 50% chance of developing HSP. Each daughter of a woman who is a carrier for X-linked HSP has a 50% chance of being a carrier (female carriers of X-linked disorders often have no symptoms).

How can it be HSP when no one else in the family has it?

There are a number of explanations why individuals who have all signs and symptoms of HSP do not have a family history of the disorder. For example, the condition may be recessive or X-linked. These forms may have passed down silently in a family for generations until finally the correct circumstances exist for someone to have the disorder.

It is also possible for someone with a dominant form of HSP to not have a family history of the disorder. Since HSP can vary greatly in severity of symptoms and age of onset, a parent may have had a very mild case and symptoms were unnoticed or attributed to other problems such as "old age" or "arthritis". Additionally, since symptoms can develop late in life, the person may have died before showing symptoms, or if still living, has not yet begun to show symptoms. Finally, it could be a new gene mutation and the affected person is the first in his family.

Can I estimate how this disorder will affect my family?

While the odds of any given conception having a gene mutation can be calculated, it is not possible to predict how severe symptoms will be or the exact age at which symptoms will first appear.

What about genetic testing for HSP?

Athena Diagnostics offers testing for mutations in the spastin gene, the most common form of dominant HSP and mutations in the atlastin gene, the most common form of dominant childhood-onset HSP. Some insurance policies will cover some or all of the fees.

These two genes are responsible for about 55% of dominant forms of HSP. Researchers believe there could be as many as thirty different forms of HSP, all caused by a different gene. Hopefully as more genes are discovered, such information will lead to greater availability of testing.

Gene tests can also be used for prenatal testing. Editor's Note: A member of our community submitted an article on gene testing. Please see Patient Forum - gene testing.

Are there risks associated with genetic testing?

There isn’t much risk in having a small amount of blood drawn but there some important issues to consider. Genetic testing is so new that the legal, ethical and medical implications are unclear. There are concerns that genetic testing can interfere with privacy, insurance eligibility or employment.

Additionally, pre-symptomatic or carrier testing of children is controversial. Many experts do not encourage testing children or adolescents at risk to determine whether they may develop HSP at some point in their lives. Some medical centers may prohibit genetic testing of minors unless there is a compelling medical reason. Even testing of adults can have unintended consequences.

It is wise to seek guidance of a genetics counselor when considering testing. Counselors may be medical professionals with special training or other individuals who have received education and certification as genetic counselors. They provide information about inheritance and the chances of having children affected by a particular inherited disease. They can also provide emotional support and make referrals to appropriate resources.

Referrals for genetics counselor can be made by neurologists. An online resource is the National Society for Genetic Counselors.

For lots of information on genetics, please visit the National Institutes of Health Genetics Home Reference.