Objective: Describe the case of a patient with adult-onset progressive ataxia and palatal tremor (PAPT) in association with a novel heterozygous mutation of the GRIN2A gene

Background: Progressive ataxia and palatal tremor (PAPT) is a clinical syndrome that may be caused by various acquired and inherited aetiologies. Lesions within the Guillain-Mollaret triangle of different aetiologies are known to account for the acquired causes, whereas mutations of the GFAP (Alexander’s disease), POLG or SPG7 genes are among the most frequently reported genetic forms

Method: Case report

Results: We present the case of a 56-year-old woman who presented with a palatal tremor and slowly progressive gait difficulties. The hyperkinetic movements were first observed by an ENT specialist who investigated her for a chronic pain of her right face. Furthermore, she  complained about double vision for about 3 years. There was no family history of neurological diseases. On clinical examination, there was a palatal tremor with oscillatory movements at a frequency of approximately 2 Hz. The rhythmic movements also involved the hypopharynx and both vocal cords. There was also a rotational nystagmus of similar frequency. Furthermore she showed some mild dysarthria, mild cerebellar oculomotor features, dysdiadochokinesia and pyramidal signs. On walking she suffered from mild gait ataxia. Her MRI showed hyperintensities of both inferior olives along with an olivary hypertrophy, but without evidence of a lesion such as a tumour. Her CSF including Whipple-PCR and antineuronal antibodies was normal. Her EEG did not show any abnormalities. A whole exome sequencing revealed a heterozygous pathogenic deletion of exon 6 of the GRIN2A gene (c.1422_1425delTTAC / p(Tyr475Thrfs*5)

Conclusion: GRIN2A mutations should be considered a potential cause for genetic forms of adult-onset PAPT. The gene was previously described in relation to the epilepsy-aphasia spectrum. Our patient shows a different phenotype as the originally described syndrome with no epilepsy and a normal EEG. However, ataxia and hyperkinetic movement disorders including orolingual movement abnormalities were mentioned as infrequent symptoms in a large series of cases with GRIN2A mutations (Strehlow et al., 2018). We propose that our case broadens the clinical spectrum of disorders due to mutations in this gene. Further studies are needed to confirm GRIN2A mutations as a cause for a predominant PAPT phenotype

References: (Strehlow et al., 2018)

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MDS Abstracts - https://www.mdsabstracts.org/abstract/progressive-ataxia-and-palatal-tremor-due-to-a-novel-heterozygous-grin2a-mutation/