Objective: We present the cases of two female FXTAS patients who both developed spasmodic dysphonia (SD), also known as laryngeal dystonia.

Background: Fragile-X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset, progressive neurodegenerative disorder that typically manifests with a postural/action tremor followed by ataxia. It is caused by a premutation (55-200 CGG trinucleotide repeats) within the FMR1 gene. The female phenotype is highly variable due to X-linkage and lyonisation.

Method: The first is an 83-year-old who presented with vocal disturbances 25 years ago and was diagnosed with SD by neurology and ear, nose, and throat (ENT) specialists. 18 years ago, she developed a head tremor and bilateral action tremor. She was advised to undergo genetic testing after her niece was diagnosed with fragile-X syndrome, which confirmed she was heterozygous for the FXTAS premutation. After a further seven years, she developed an ataxic gait. An MRI brain scan showed moderate atrophy of the cerebellar vermis and superior cerebellar hemispheres. She developed left-sided anterolateral thigh pain and footdrop three years later; nerve conduction tests confirmed the presence of a length-dependent sensorimotor axonal neuropathy, an additional part of the FXTAS syndrome.
The second is a 79-year-old, with premature ovarian insufficiency (POI) at the age of 38, who presented 10 years ago with a mild head tremor and left-sided upper limb postural tremor. A year later, she developed an ataxic gait and vocal tremor. Her son was diagnosed with fragile-X syndrome at the time, which triggered her to be tested for the condition. She was found to be heterozygous for the FXTAS premutation. An MRI brain scan was unremarkable. Over the next four years, her voice, became “breathy” and quiet, consistent with SD. Flexible laryngoscopy was arranged and confirmed a pharyngeal tongue-based tremor with simultaneous supraglottic tremor.

Results: This is the second report of SD in female patients with FXTAS (previously described by Horvath et al, 2007).SD is the involuntary contraction of the laryngeal musculature that leads to vocal changes and may lead to difficulty with breathing/swallowing.

Conclusion: Clinicians should consider FXTAS in females who present with vocal tremors, especially if there is a history of POI, as the phenotype in females maybe wider than has previously been appreciated.

References: Horvath J, Morris M, Bottani A, Moix I, Delavelle J, Burkhard P. Expanding the phenotype of fragile X-associated tremor/ataxia syndrome: A new female case. Movement Disorders. 2007;22(11):1677-1678.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/widening-the-phenotype-of-fxtas-in-females-spasmodic-dysphonia-in-two-patients/