PRKRAP1 Pseudogene Complicating the Diagnosis of Young‐Onset Dystonia Due to PRKRA Gene Disease‐Causing Variants (DYT‐PRKRA)

Abstract

A genetic etiology of isolated dystonia is suspected if there is an early-onset dystonia or a positive family history. However, the current overall yield of a genetic etiological diagnosis remains below 30%. 1 We present a case of a 13-year-old Caucasian male, the only child from a non-consanguineous couple, without family history of neurological diseases, with no previous medical history, and normal psychomotor development.At the age of 8, he started developing involuntary twisting movements that resulted in abnormal postures, first affecting his right lower-limb, then progressing to cervical region and right upper-limb, mildly impairing his daily activities and manifesting mostly while exercising. At 9 years old, the dystonic movements progressed to left hemi-body and axial region, and he developed a slight slurred speech. There were no cognitive or behavioral symptoms, and he maintained school performance with adjustments.At the age of 11, his examination revealed a generalized dystonia (Fig. 1, Video 1) resulting in gait impairment, frequent falls, and important disruption of daily activities. There were no ophthalmological abnormalities, other cranial nerve signs, pyramidal signs, parkinsonism, cerebellar features, or myoclonus.Initial therapeutic management included levodopa/carbidopa (up to 300 mg per day), clonazepam, baclofen, and tetrabenazine, all without sustained response. Complementary examination included a normal brain and cervical magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) analysis. Laboratory work-up