Clinical and Genetic Overview of Paroxysmal Movement Disorders and Episodic Ataxias

Abstract

<jats:p>Paroxysmal movement disorders (PMDs) are rare neurological diseases typically manifesting with intermittent attacks of abnormal involuntary movements. Two main categories of PMDs are recognized based on the phenomenology: Paroxysmal dyskinesias (PxDs) are characterized by transient episodes hyperkinetic movement disorders, while attacks of cerebellar dysfunction are the hallmark of episodic ataxias (EAs). From an etiological point of view, both primary (genetic) and secondary (acquired) causes of PMDs are known. Recognition and diagnosis of PMDs is based on personal and familial medical history, physical examination, detailed reconstruction of ictal phenomenology, neuroimaging, and genetic analysis. Neurophysiological or laboratory tests are reserved for selected cases. Genetic knowledge of PMDs has been largely incremented by the advent of next generation sequencing (NGS) methodologies. The wide number of genes involved in the pathogenesis of PMDs reflects a high complexity of molecular bases of neurotransmission in cerebellar and basal ganglia circuits. In consideration of the broad genetic and phenotypic heterogeneity, a NGS approach by targeted panel for movement disorders, clinical or whole exome sequencing should be preferred, whenever possible, to a single gene approach, in order to increase diagnostic rate. This review is focused on clinical and genetic features of PMDs with the aim to (1) help clinicians to recognize, diagnose and treat patients with PMDs as well as to (2) provide an overview of genes and molecular mechanisms underlying these intriguing neurogenetic disorders.</jats:p>

A Child Who Suddenly Freezes While Trying to Cross Crosswalks—Unique Clinical Manifestation of Paroxysmal Kinesigenic Dyskinesia: A Case Report

“…Additionally, other than PRRT2 , several genes are related to PKD. Therefore, when patients with symptoms of PKD test negative for PRRT2 mutation, mutations in other genes including CAN8A , DEPDC5 , KCNA1 , KCNMA1 , PNKD , and SLC2A1 , should be considered [ 12 ].…”

Recommendations for the diagnosis and treatment of paroxysmal kinesigenic dyskinesia: an expert consensus in China

“…h. Benign paroxysmal torticollis (BPT) [62] BPT is present as recurrent episodes of abnormal, painless head postures, alternating from side to side. Attacks may last from a few minutes to several days.…”

“…i. Transient dystonia of infancy [62] Transient dystonia of infancy consists of paroxysmal episodes of abnormal upper limb posture, with occasional concomitant involvement of the trunk and a single lower limb [64]. The interictal examination and neuroimages are normal.…”

“…j. Benign myoclonus of early infancy (BMEI) [62] BMEI was originally described as a nonepileptic paroxysmal motor disorder characterized by the occurrence of myoclonic jerks of the head and/or of the upper limbs, usually occurring in clusters and mimicking infantile spasms. Consciousness is preserved during attacks, which usually occur during wakefulness and more rarely during sleep or drowsiness.…”

Is it really a seizure? The challenge of paroxysmal nonepileptic events in young infants

“…19) Like other paroxysmal movement disorders, some PNE are also associated with genetic mutations. 20) The CACNA1A gene encodes the α1A subunit of the voltage gated calcium channel. The mutation of this gene is associated with early infantile epileptic encephalopathy, episodic ataxia, migraine and spinocerebellar ataxia.…”