About 90-95% percent of cases of ALS are
not inherited and occur in individuals with no history of the disease in their family. The remaining 5-10% of cases are
familial, and are thought to be caused by
mutations in any one of several
genes. The inheritance pattern associated with familial ALS varies depending on the disease-causing gene involved.
Most familial cases are inherited in an
autosomal dominant manner. This means that only one altered (mutated) copy of the disease-causing gene in each
cell is sufficient to cause the condition. In most of these cases, an affected individual has one parent with the condition. When an individual with an autosomal dominant form of ALS has children, each child has a 50% (1 in 2) risk to inherited the mutated copy of the gene and be affected.
Less frequently, ALS is inherited in an
autosomal recessive manner. In autosomal recessive inheritance, both copies of the disease-causing gene (typically one copy inherited from each parent) must have a mutation for the individual to be affected. The parents of an individual with an autosomal recessive condition, who presumably each carry one mutated copy of the gene, are referred to as
carriers. Carriers typically do not have any signs or symptoms of the condition. When two carriers for the same condition are having children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each parent, and a 25% risk to not have the condition
and not be a carrier. Autosomal recessive forms of ALS may be mistaken for non-inherited (sporadic) forms due to having a negative
family history of the condition.
In rare cases, ALS is inherited in an
X-linked dominant manner. This occurs when the disease-causing gene is located on the
X chromosome (a
sex chromosome). Although females have 2 X
chromosomes, having a mutation in one X chromosome is still sufficient to cause the condition. Males who have a mutation (and only one X chromosome) will have the condition. Usually, males with an X-linked dominant form of ALS experience more severe symptoms than females with the same form.
Some individuals who do inherit a mutation known to cause ALS never develop signs and symptoms of ALS, although the reason for this is unclear. This phenomenon is referred to as
reduced penetrance.
[1]
Last updated: 5/9/2017
Age of onset alone is not a reliable predictor of the form of ALS that an individual has. Furthermore, if an individual is found to have an inherited form of ALS, the specific inheritance pattern would depend on the disease-causing gene involved. Establishing the specific subtype of ALS in a given individual usually involves obtaining family history and performing molecular
genetic testing.
[2]Onset of ALS may occur any time from the teenage years up to the late 80s.
[3] The average age of onset for sporadic (non-inherited) ALS has been estimated to be around 56 to 65 years (estimates vary among sources).
[2][4][3] The average age of onset for familial ALS is approximately 46 years.
[2][3] However, onset of either form may occur years before or after these average ages.
Last updated: 1/11/2013
Last updated: 12/6/2017