The Dystonias

Abstract

PURPOSE OF REVIEW This article provides a summary of the state of the art in the diagnosis, classification, etiologies, and treatment of dystonia. RECENT FINDINGS Although many different clinical manifestations of dystonia have been recognized for decades, it is only in the past 5 years that a broadly accepted approach has emerged for classifying them into specific subgroups. The new classification system aids clinical recognition and diagnosis by focusing on key clinical features that help distinguish the many subtypes. In the past few years, major advances have been made in the discovery of new genes as well as advances in our understanding of the biological processes involved. These advances have led to major changes in strategies for diagnosis of the inherited dystonias. An emerging trend is to move away from heavy reliance on the phenotype to target diagnostic testing toward a broader approach that involves large gene panels or whole exome sequencing. SUMMARY The dystonias are a large family of phenotypically and etiologically diverse disorders. The diagnosis of these disorders depends on clinical recognition of characteristic clinical features. Symptomatic treatments are useful for all forms of dystonia and include oral medications, botulinum toxins, and surgical procedures. Determination of etiology is becoming increasingly important because the number of disorders is growing and more specific and sometimes disease-modifying therapies now exist.

The Dystonia Coalition: A Multicenter Network for Clinical and Translational Studies

“…Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. Dystonia is not a single disorder but a family of heterogenous disorders with varied clinical manifestations and many different causes (2,3).…”

“…There are many known etiologies for dystonia. They include lesions of the nervous system, exposure to drugs or medications, infections and autoimmune processes, and other causes (2)(3)(4). However, for the vast majority of cases of isolated dystonia, a cause cannot be identified, even after extensive laboratory testing.…”

“…This observation points to inherited mechanisms. More than 100 genes capable of causing dystonia are known, most of which cause early-onset or combined forms of dystonia (2,4,5). Recent whole-exome sequencing studies have suggested that an etiology can be identified in ∼20% of cases, depending on the associated clinical features (6,7).…”

Autoimmune and Inflammatory Mechanisms in Cervical Dystonia

“…Cervical dystonia (CD) is characterized by excessive involuntary contraction of neck muscles leading to abnormal postures and movements of the head, often with neck pain 21 . Etiologies are heterogeneous and include focal or degenerative lesions of the nervous system, exposure to drugs or medications, infections, and others.…”

Delineation of the Clinical Features and Treatment Response of Oromandibular Dystonia: A Multicenter Summary of 2,057 Cases

“…The time from onset of symptoms to diagnosis in the most common forms of dystonia can be up to 6 years, and this delay is believed to be even longer in OMD. 5,6 Also due to its rarity, much of our understanding is based on case reports or relatively small series from expert centers. Some of these focused on idiopathic cases, others included acquired forms, and some included a high representation of inherited disorders with OMD, such as X-linked dystonia parkinsonism.…”