Open Access Research article

Nystagmus as an early ocular alteration in Machado-Joseph disease (MJD/SCA3)

Mafalda Raposo12*, João Vasconcelos3, Conceição Bettencourt24, Teresa Kay5, Paula Coutinho6 and Manuela Lima12

Author Affiliations

1 Center of Research in Natural Resources (CIRN), University of the Azores, Rua Mãe de Deus, Apartado 1422, 9501-801 Ponta Delgada, Portugal

2 Institute for Molecular and Cellular Biology (IBMC), University of Porto, Porto, Portugal

3 Department of Neurology, Hospital do Divino Espírito Santo, Ponta Delgada, Portugal

4 Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK

5 Department of Clinical Genetics, Hospital of D. Estefania, Lisbon, Portugal

6 CGPP, Institute for Molecular and Cellular Biology (IBMC), University of Porto, Porto, Portugal

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BMC Neurology 2014, 14:17  doi:10.1186/1471-2377-14-17

Published: 22 January 2014



Machado-Joseph disease (MJD), also named spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant ataxia worldwide. Although nystagmus is one of the most frequently reported ocular alterations in MJD patients its behaviour during the course of the disease, namely in its early stages, has only recently started to be investigated. The main goal of this work was to characterize the frequency of nystagmus in symptomatic and presymptomatic carriers of the MJD mutation, and investigate its usefulness as an early indicator of the disease.


We conducted an observational study of Azorean MJD family members, comprising a total of 158 subjects which underwent neurological evaluation. Sixty eight were clinically and molecularly diagnosed with MJD, 48 were confirmed asymptomatic carriers and 42 were confirmed non-carriers of the MJD mutation. The frequency of nystagmus was calculated for the 3 groups.


Nystagmus was present in 88% of the MJD patients. Seventeen percent of the at-risk subjects with a carrier result in the molecular test and none of the 42 individuals who received a non-carrier test result displayed nystagmus (p < 0.006). Although not reaching statistical significance, symptomatic subjects showing nystagmus had a tendency for a higher length of the CAG tract in the expanded allele, when compared to individuals who did not have nystagmus.


The frequency of nystagmus in asymptomatic carriers and its absence in non-carriers of the mutation, suggests that nystagmus may appear before gait disturbance and can thus be considered an early sign of MJD.

Spinocerebellar ataxia; Presymptomatic subjects; Clinical trials