John K. Fink,
SPF Medical Advisor
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
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
Reference for information about genetics.
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).
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
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.
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
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?
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 -
Are there risks associated with genetic
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.