Objective: We present a case of a patient with spinocerebellar ataxia symptoms associated with a previously unknown mutation of the SYT14 gene.

Background: Spinocerebellar ataxias (SCAs) are a group of inherited neurodegenerative disorders associated with genetic mutations, most commonly trinucleotide repeat expansions.

Method: A 76-year-old female presents to the clinic and noted to have orthostatic hypotension, cervical dystonia with left laterocollis and anterocollis, asymmetric bradykinesia and rigidity worse on her left-sided extremities, ataxic speech, and upbeat and rotational nystagmus bilaterally on exam. MRI brain was negative for intracranial structural abnormalities such as brainstem or cerebellar atrophy. DaTScan was negative for evidence of dopaminergic degeneration. Skin biopsy was negative for alpha-synuclein. Extensive laboratory workup including basic sensory neuropathy and inflammatory labs, autoimmune/paraneoplastic antibody panels were unremarkable. Serum ferritin level was low at 9 ng/mL

Family history was significant for neuropathy, balance and gait disturbances in her mother and maternal grandmother. Genetic testing was positive for a heterozygous variant of c.1071A>G (p.Ala357Ala) locus on the SYT14 gene of uncertain significance.

 ​​​​

Results: Synaptotagmin XIV is a protein encoded by the SYT14 gene expressed in the Purkinje cells of the cerebellum. Very little is known about mutations in this gene and its association with spinocerebellar ataxia. Only 2 cases of cerebellar ataxia associated with this gene are reported in literature, both associated with a homozygous mutation at p.Gly484Asp (c.1451 G>A) present in two siblings with signs of cerebellar ataxia in childhood and progressing mid-life. Other mutations in SYT14 have been associated with cerebral atrophy, macrocephaly, seizures and developmental delay, as well as with familial schizophrenia and bipolar disorder. Currently there are no reported instances of a mutation at the c.1071A>G (p.Ala357Ala) locus associated with clinical symptoms.

Conclusion: Workup for neurodegenerative disorders should include genetic testing given their strong association with genetic mutations. More widespread testing can help to identify mutations such as the one in our patient and clarify their clinical relevance.

« Back to 2025 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/refractory-orthostatic-hypotension-anterocollis-predominant-cervical-dystonia-and-parkinsonism-associated-with-a-previously-undiscovered-syt14-gene-mutation/