Tremor and Craniofacial Dystonia Preceding Ataxia in SCA43: Expanding the Phenotypic Spectrum of MME-related Ataxia.

Spinocerebellar ataxia type 43 (SCA43) is a rare autosomal dominant ataxia caused by pathogenic variants in the MME gene and typically presents with late-onset gait ataxia and sensory neuropathy. Hyperkinetic movement disorders are uncommon, and prominent craniofacial orobuccolingual dystonia-dominant presentations have not been documented. We report a 63-year-old woman who developed progressive orobuccolingual dystonia and stereotypical choreiform movements of the right hand several years before the onset of gait ataxia. These involuntary movements significantly interfered with feeding and speech and were initially isolated, creating diagnostic uncertainty. Examination revealed prominent craniofacial dyskinesias, postural tremor, gait ataxia, and distal lower limbs vibration loss with otherwise normal sensory modalities. MRI showed chronic small-vessel changes without cerebellar atrophy, and nerve conduction studies were normal. Whole-exome sequencing identified a heterozygous MME exon 21 variant (NM_000902.4:c.2067C > A; p.Asn689Lys), classified as a variant of uncertain significance, which segregated with disease in two affected sisters and was present in a minimally symptomatic son with a long-standing mild head tremor, supporting autosomal dominant inheritance. The phenotype was notable for the temporal dissociation between involuntary movements and cerebellar signs, normal electrophysiology despite sensory impairment, and the absence of cerebellar atrophy on imaging. This case expands the clinical spectrum of SCA43 by demonstrating that a hyperkinetic movement disorder phenotype, including tremor, choreiform movements, and craniofacial dystonia, may precede overt cerebellar dysfunction by several years. Recognition of such atypical manifestations is essential to avoid misdiagnosis and to prompt timely genetic evaluation in patients presenting with mixed or unexplained movement disorders, particularly in the presence of a supportive family history.