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Page 10 of 31 Guerra et al. J Transl Genet Genom 2019;3:9. I https://doi.org/10.20517/jtgg.2018.03

disturbances are usually less severe than in spinocerebellar ataxia and are almost exclusively due to
cerebellar degeneration. No relationship between the severity of dysarthria and body ataxia exists. Some
characteristic features of speech show a difficulty in maintaining a constant tone, with vocal instability
[25]
during the speech or a reduction in the maximum speed of syllable repetition .
Spinocerebellar ataxia (SCA): SCA3 is the most common autosomal dominant ataxia worldwide, followed by
SCA1, 2, 6 and 7. The phenotype of SCAs varies and can affect only the cerebellum or other brain structures.
For example, SCA6 and SCA5 generate a pure cerebellar syndrome due to cortical ataxia, while SCA1 and
[20]
SCA3 have a diffuse affectation .

SCA1 (ATXN1 6p22.3) has a greater effect on voice dimensions. Rough and strangled voice are predictors of
[23]
disease severity .
SCA3 (ATXN3 locus 14q32.12 gene) affects specifically the regularity of diadochokinetic syllable repetitions
(DSR) if compared to the rest of hereditary ataxias. Also, the characteristics of the non-verbal oral motor
deteriorate significantly in SCA3. The more widespread process of the brain and brain stem degeneration in
[22]
SCA3 may compromise non-speech tasks, such as DSR to a greater degree than other ataxias .
SCA5 (SPTBN2 locus 11q13.2 gene) usually generates less dysarthric involvement than the rest of
[23]
spinocerebellar ataxias. Unlike SCA1, only the strangled voice is a prognostic factor in the disease severity .

Articulatory speech disorders especially affect to patients with SCA6 (CACNA1A gene, locus 19p13.13).
Speech parameter degradations (frequency and modulation) are worse at SCA6. The speech parameters
in prosodic modulation are also particularly vulnerable. It is due to neurodegeneration in SCA6, which is
largely (though not only) confined to the cerebellum. In contrast to many other types of SCA, cerebellar
degeneration largely implicates the cerebellar cortex [22,23] .

Regarding SCA7 (ATXN7 gene, locus 3p14.1), voice deterioration is unrelated to age at onset and the
length of the cytosine-adenine-guanine triplet tract. Surprisingly, the results of the acoustic analysis (jitter
and shimmer) correlate with Inventory of Non-Ataxia Symptoms, but not with Scale for the Evaluation
and Rating of Ataxia scores, which implies that voice deterioration results from extra-cerebellar clinical
[24]
manifestations . No other relevant studies that specifically assess the characteristics of dysarthria in other
ataxic variants have been reported.

Spastic dysarthria
Spastic dysarthria is related to alterations in the upper motor neuron system. Unilateral involvement of the
upper motor neuron is usually classified as a separate type. Patients have slow-moving speech, a tense voice
[11]
[26]
and multiple breaks in pitch . Examples of spastic dysarthria are hereditary spastic paraplegias and other
[27]
mixed expression disorders such as multiple sclerosis .
Multiple sclerosis (MS): Multiple sclerosis is a demyelinating condition of unknown etiology in which
environmental and genetic factors are involved. It generates a spastic, ataxic or more frequently mixed (spastic-
ataxic) dysarthria. Studies of dysarthria in MS show a prevalence ranging from 41% to 51%. The main speech
[27]
disturbances are in volume control, rough voice quality and imprecise articulation . It may show cognitive
deficits such as slowed information processing speed, impaired working memory and reduced information
[28]
processing efficiency. It can also manifest as a subtle, non-phasic high-level language deficits . Assessment of
[29]
dysarthria may be helpful in controlling clinical and progression of a subclinical disease .

A genetic susceptibility to the development of multiple sclerosis may exist, associated with certain HLA
genes, including HLA-A, HLA-DRB1, HLA-DQB1, HLA-DQB1, HLA-DRA, on chromosome 6p21.3. Other
haplotypes identified are HLA-DRB1* 1501-DQB1* 0602 (HLA-DR15). Additional MS susceptibility loci