Seizures as presenting and prominent symptom in chorea‐acanthocytosis with c.2343del VPS13A gene mutation

Abstract

Objective: The aim of the study was to characterize the clinical features of nine patients in three families with chorea-acanthocytosis (ChAc) sharing the same rare c.2343del mutation in the VPS13A gene. Methods: Genetic test results, clinical description, magnetic resonance imaging (MRI), and electroencephalography (EEG), as well as laboratory results are summarized. Results: ChAc is a rare genetic disorder characterized by hyperkinetic movements, seizures, cognitive decline, neuropsychiatric symptoms, and acanthocytes on peripheral blood smear. This unique cohort of nine patients is characterized by seizures as a first and prominent symptom. In our patients, other features of ChAc appeared later, including tics, other movement disorders, dysarthria, and mild to moderate cognitive decline. Significance: Patients with chorea-acanthocytosis carrying the described rare mutation can present with focal, treatment-resistant seizures.

Novel VPS13A Gene Mutations Identified in Patients Diagnosed with Chorea-acanthocytosis (ChAc): Case Presentation and Literature Review

“…In comparison, orofacial and oromandibular chorea are typical symptom in both affected patients in our study, but the presenting symptom in patient 1 is GTCS while in patient 2 is bruxism (see Tables 1 , 2 ). Given the novel and disparate VPS13A gene mutations identified in patient 1 and patient 2, it can be presumed that particular incipient symptoms may be associated with some specific VPS13A mutations, just as corroborated by the relevance of c.2343del mutation to epilepsy in Israeli families (Benninger et al, 2016). Nevertheless, restricted by the sample sizes in this study, it is imperative to investigate the intriguing proposition of genotype–phenotype correlation in larger ChAc groups in future study.…”

“…In general, seizure are mostly antiepileptic drugs (AEDs) sensitive GTCS in ChAc, just as proven in patient 1, but simple and complex partial seizures have been described as well (Al-Asmi et al, 2005; Walker et al, 2007). For example, a recent study had identified a rare c.2343del VPS13A gene mutation in three Israeli families, in which most affected individuals presented seizures as the first and dominant symptom (Benninger et al, 2016). Moreover, seizures of this type could be of temporal lobe origin and were AEDs resistant in five out of nine patients (Benninger et al, 2016).…”

“…For example, a recent study had identified a rare c.2343del VPS13A gene mutation in three Israeli families, in which most affected individuals presented seizures as the first and dominant symptom (Benninger et al, 2016). Moreover, seizures of this type could be of temporal lobe origin and were AEDs resistant in five out of nine patients (Benninger et al, 2016). Peripheral sensorimotor neuropathy with the absence of deep tendon reflexes is common in NA, and it can be no easy to differentiate from motor neuron disease (Neutel et al, 2012).…”

“…What is interesting is that a recent study revealed a rare c.2343del mutation in three ChAc Israeli families in which seizures present as the premier and prominent symptoms (Benninger et al, 2016). Moreover, the seizures presented in these families were, in large part, of temporal origin and partly AEDs resistant (Benninger et al, 2016).…”

“…Moreover, the seizures presented in these families were, in large part, of temporal origin and partly AEDs resistant (Benninger et al, 2016). A retrospective review of ever published literatures indeed indicates the presence of epilepsy at early stages of NA (Hardie et al, 1991; Schwartz et al, 1992; Kazis et al, 1995; Aasly et al, 1999; Al-Asmi et al, 2005), but scarcely in the case of ChAc.…”