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The prevalence varies according to region and ethnic population. In the USA the estimated prevalence in the general population is approximately 1/30,000, whilst in Europe the estimated prevalence ranges from 1/ 200,000-330,000, although precise figures are currently not available. The estimated prevalence in the Ashkenazi Jewish population is much higher at 1/3,000-9,000, due to a founder effect.

Symptoms typically develop first in an arm or leg with dystonic muscle contractions in middle to late childhood, and may first become apparent with specific actions such as writing or walking. In approximately 60-70% of patients, the disease progresses to other body regions (multifocal or generalized dystonia) within about five years, involving at least one leg and one arm, and often axial muscles. Spread to craniocervical muscles may rarely occur. Distribution and severity of symptoms vary widely between affected individuals and even within the same family. This type of dystonia is not associated with other neurologic or systemic abnormalities.

The majority of cases are caused by a heterozygous deletion of three base pairs (GAG) in the /TOR1A gene (chromosome 9q34). This gene encodes the protein torsinA, which is ubiquitously expressed and, as an AAA+ ATPase, appears to play a role in various cellular compartments (cytoskeletal dynamics, vesicle fusion, membrane trafficking, and protein folding). The protein shuttles between the endoplasmic reticulum (ER) and the nuclear envelope, where it plays a role in ER-associated degradation, rendering cells less sensitive to ER stress.

The diagnosis is established in a proband by identification of a heterozygous TOR1A three base-pair deletion, c.907_909delGAG, which is the only definitely pathogenic variant in the TOR1A gene identified to date.

Differential diagnosis includes other forms of isolated dystonia such as Dopa-responsive dystonia (due to either GCH1, SPR, TH), Primary dystonia, DYT6 type (THAP1), and Autosomal dominant focal dystonia, DYT25 type (GNAL). Whilst presenting symptoms may be similar, DYT25 is frequently distinguished by adult-onset focal dystonia, whereas individuals with DYT6 dystonia frequently have prominent cranio-cervical and laryngeal involvement.

The pattern of inheritance is autosomal dominant with low penetrance (approximately 30% of carriers become symptomatic) and variable expressivity with respect to age, site of onset, and progression. Molecular testing and genetic counseling are recommended for individuals with an age of onset below 26 years, and may also be considered in those with onset after 26 years who have a relative with typical early-onset isolated dystonia.

Treatment options include botulinum toxin injections for focal symptoms and pharmacological therapy such as anticholinergics (most commonly trihexyphenidyl) for generalized dystonia. In severe cases with medically refractory early-onset dystonia, surgical approaches, especially deep brain stimulation (DBS) of the internal globus pallidus (GPi) or, in some cases, intrathecal baclofen application should be considered. In recent years, GPi-DBS has been established as an important treatment option for medically refractory isolated generalized dystonia, with most individuals experiencing good or sometimes even dramatic improvement.

All patients have normal cognitive function, and despite a high rate of generalization of dystonic symptoms, approximately 75% of patients are able to maintain ambulation and independence, and therefore a comparatively good quality of life, with modern treatment modalities. In children and adults with severe, medically refractory dystonia, GPi-DBS should be considered early in the course of the disease, since shorter disease duration has been correlated with improved outcomes.