An increasing number of repeat expansion disorders have been found to cause both rare and common neurological disease. This is exemplified in recent discoveries of novel repeat expansions underlying a significant proportion of several late-onset neurodegenerative disorders, such as CANVAS (cerebellar ataxia, neuropathy and vestibular areflexia syndrome) and spinocerebellar ataxia type 27B. Most of the 60 described repeat expansion disorders to date are associated with neurological disease, providing substantial challenges for diagnosis, but also opportunities for management in a clinical neurology setting. Commonalities in clinical presentation, overarching diagnostic features and similarities in the approach to genetic testing justify considering these disorders collectively based on their unifying causative mechanism. In this review, we discuss the characteristics and diagnostic challenges of repeat expansion disorders for the neurologist and provide examples to highlight their clinical heterogeneity. With the ready availability of clinical-grade whole-genome sequencing for molecular diagnosis, we discuss the current approaches to testing for repeat expansion disorders and application in clinical practice.
We describe a 63-year-old man diagnosed with sporadic Creutzfeldt-Jakob disease (sCJD), specifically sporadic fatal insomnia, confirmed through real-time quaking-induced conversion (RT-QuIC) analysis of cerebrospinal fluid and polysomnography. He presented with rapid cognitive decline, behavioural changes, sleep disturbances and dysautonomic symptoms. Initial MR imaging, electroencephalogram and cerebrospinal fluid analyses were inconclusive, highlighting the difficulty in diagnosing this rare subtype of CJD. Clinical evaluation is fundamental in defining the diagnosis of sCJD. When clinical suspicion is strong, the diagnostic work-up should be continued. In this case, the combination of comprehensive clinical evaluations and advanced diagnostic tools, including RT-QuIC and polysomnography, proved essential in making a definitive diagnosis.
Hypertension is the leading cause of stroke in the UK and worldwide. In recent years, stroke incidence has increased by 30%-41.5% in people aged under 64 years, with the prevalence of hypertension increasing by 4%-11%. Given that 5%-10% of people with hypertension in the general population have an underlying cause for their elevated blood pressure, it is important that all clinicians should maintain a high clinical suspicion for secondary hypertension. This review provides a clinical perspective of when to consider the underlying causes of secondary hypertension, with investigation algorithms for patients presenting with stroke and hypertension. Early involvement of hypertension specialist services is important to identify secondary causes of hypertension, as its effective control reduces cardiovascular-associated morbidity.
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