Timothy C. Hain, MD Page last modified: November 29, 2018
See also: spinocerebellar ataxia page.
SCA3, which is dominantly inherited, is also known as Machado-Joseph disease, see also the OMIM entry. There are many articles about SCA3.
SCA3 is characterized pathologically by spinopontine atrophy, degeneration of the dentate nuclei, vestibular nuclei, extrapyramidal structures, motor cranial nerves, anterior horn cells, and posterior root ganglion, but sparing of the cerebellar cortex. (see Koeppen et al, 2018).
Clinically, SCA3 is characterized by cerebellar ataxia, pyramidal tract signs and progressive external ophthalmoplegia. There is often lid retraction producing a characteristic staring expression, termed bulging eyes. (Although this is reported in the literature, we have never encountered this finding in our own clinic population -- and we don't think that this is required).
Gaze evoked nystagmus is often present in SCA3 (Rivaud-Pechoux et al, 1998). The movie above illustrates both GEN as well as Rebound nystagmus. Restless legs occurs in 45% (Schols, 1998). Fascial and tongue fasciculations are also sometimes present.
MJD was first described in families of Portuguese origin, but it has been documented in many families not of Portuguese ancestry. Several large studies have demonstrated that MJD accounts for about 84% of autosomal dominant SCA in Portuguese, 50% in Germans, and 11 to 29% in other non-Portuguese ethnic populations.
The MJD locus has been mapped to chromosome 14q31.1, and the mutation has been demonstrated to be an expansion of a CAG repeat. (Soong et al, 1997). Atrophy of the brainstem and vermis in MJD is closely correlated with both the size of the CAG repeat as well as patient age (Onodera et al, 1998).
Genetic testing is the usual way that MJD is diagnosed. Clinical testing can be suggestive but there is overlap between many other SCAs. VEMP testing (neck) may be reduced in MJD (SCA-3). We illustrate a case of this here.
Treatment: Is mainly supportive.
- McLoughlin et al (2018) recently published concerning an investigational treatment in mice, that is not suitable for use in humans.