What is Spinocerebellar Ataxia Type 27B?

Spinocerebellar Ataxia Type 27B (SCA27B) is one specific type of ataxia among a group of inherited and progressive neurodegenerative diseases of the central nervous system. In SCA27B, a genetic mutation leads to dysfunction of the cerebellum (the motor coordination center of the brain). Brain imaging may show atrophy (shrinkage) of the cerebellum. SCA27B is caused by a GAA trinucleonide repeat expansion in the FGF14 gene - more below in section: Why does my genetic testing report “repeat lengths”?

What are the symptoms of SCA27B?

Ataxia is a word that describes someone as uncoordinated. Like other forms of inherited ataxia, SCA27B is marked by incoordination. It is most common for someone to have impaired walking ability (gait ataxia) and impaired movement of their arms and legs (appendicular ataxia). It is also common for people to experience other symptoms such as spontaneous eye movements (e.g. gaze-evoked horizontal nystagmus or downbeat nystagmus), room-spinning dizziness (vertigo), difficulties with speech (cerebellar dysarthria), double vision (diplopia), and impaired fine motor skills. Some may experience bouncing vision with head movement, tremors, muscle stiffness, or some loss of feeling in the toes or fingers. These symptoms may manifest in people in different ways and with different severities.

Particularly early in the disease, these symptoms may not be present in every person all the time; rather, many people only have these symptoms in episodes lasting minutes to days. Episodes may recur on a daily to a monthly basis. Alcohol, exercise, and caffeine may trigger these episodes. As the disease progresses, the symptoms become more and more pronounced and eventually become present all the time. People may require a walking aid or a wheelchair.

How is SCA27B acquired?

SCA27B is an autosomal dominant genetic disorder which means it is directly passed down from one generation to the next. Only one parent has to have SCA27B for the child to inherit the condition. Each child of a parent with SCA27B has a 50% chance of inheriting the GAA repeat within the FGF14 gene that causes SCA27B. Some individuals with SCA27B may have no family history of ataxia due to a variety of reasons: 1) their parent died before they exhibited symptoms of SCA27B, 2) their parent had a GAA repeat length in the “incomplete penetrance” range of 250-299 or lower (see next section for more on incomplete penetrance), 3) the mutation newly arose in that individual.

Why does my genetic testing report “repeat lengths”?

Genes are composed of molecules called nucleotides which are linked closely together in chains. Each nucleotide can be named with one of these four letters: C, A, G, or T. These individual nucleotides then can be combined to form trinucleotides: three letters next to each other. Sometimes these trinucleotides are repeated in a series. For example, if multiple GAA trinucleotides occur repeatedly, that segment of the genetic code could be GAAGAAGAA, etc.

In SCA27B, the abnormality responsible for this disease is an expansion in the number of repeated GAA trinucleotides found in the first intron (non-coding region) of the FGF14 gene on chromosome 13. When the trinucleotide GAA is repeated 250-299 times, then one is considered to be affected by SCA27B but may or may not display symptoms (incomplete penetrance). There is discussion that the threshold for incomplete penetrance may even be lower (200-249 repeats). In individuals with repeat lengths of 300 or more, progressive symptoms of SCA27B will develop (full penetrance). The number of repeats may affect progression of the disease – when the number of repeats is larger, disease symptoms may start earlier, but this is not always the case. This is the subject of much ongoing SCA27B research. Other genetic, lifestyle, and/or environmental factors may have a greater influence on the age of onset and severity of symptoms than solely the repeat number.

In our family, legend has it that the disease can be passed through the mother, but not the father. Is this true?

SCA27B is unusual in that the number of relevant trinucleotide repeats can vary quite a bit, even within a family. Scientists have observed that the number of repeats may stay the same or increase when passed through the mother but may stay the same or decrease when passed through the father. As a result, the child of an affected mother may have a disease course that is more rapid and severe, whereas children of an affected father may have milder, more slowly progressive disease. In some cases, if the number of repeats is low enough — below the 250 repeat threshold — the child may not exhibit symptoms at all.

What is the prognosis for SCA27B?

The prognosis is still being determined as we gather more patient data surrounding the disease. Although SCA27B can be profoundly life-altering, it does not appear to be life-shortening. As mentioned in the section on “repeat lengths”, there can be variability in disease severity related to differing lengths of the GAA trinucleotide repeat in the FGF14 gene responsible for SCA27B and/or other genetic, lifestyle, or environmental influences. More research is underway to determine how the repeat length and other factors affect the age of onset and severity of symptoms.