The Spectrum of Non-Parkinsonian Tremor: A Registry at a Tertiary Care Teaching Institute.

Background: Tremors other than those associated with Parkinson's disease (non-parkinsonian tremor) are commonly observed in clinical settings. However, their frequency and clinical characteristics have rarely been reported. Objectives: To classify non-parkinsonian tremors based on the consensus statement on the classification of tremors, from the task force of the International Parkinson and Movement Disorder Society published in 2018. Methods: A prospective registry at a tertiary care teaching institute. Results: A total of 475 patients with non-parkinsonian tremors were recruited for the study. 67.57% (n = 321) of our patients were male and a family history of tremor was present in 20.84% (n = 99) of patients. Dystonic tremor (DT) was the most common non-parkinsonian tremor (33.26%). 27.78% of patients fulfilled the new classification criteria for essential tremor, with 13.47% classified as pure ET (ET) and 14.31% exhibiting neurological soft signs, leading to the classification of ET plus (ETP). Patients with ETP had more family history (57.35%) [vs DT (26.48%, p = 0.00004) and ET (10.93%, p = 0.00003], longer duration of disease [mean ± standard deviation (SD) = 9.53 ± 8.64 years] [vs DT (5.60 ± 5.93, p = 0.0003) and ET (6.38 ± 5.97, p = 0.01) years], and more severe tremor as measured by the essential tremor rating assessment scale total score [mean ± SD = 27.42 ± 11.70] [vs DT (23.50 ± 8.62, p = 0.007) and ET (22.12 ± 8.19, p = 0.007)] compared with patients with DT and ET. Conclusions: DT was the most common cause of non-parkinsonian tremor in our registry followed by essential tremor syndrome. ETP was more common than ET.

Tremor in Primary Monogenic Dystonia.

PURPOSE OF REVIEW: Tremor is an important phenotypic feature of dystonia with wide variability in the reported prevalence ranging from 14 to 86.67%. This variability may be due to the types of dystonia patients reported in different studies. This article reviews research articles reporting tremor in primary monogenic dystonia. RECENT FINDINGS: We searched the MDS gene data and selected all research articles reporting tremor in primary monogenic dystonia. Tremor was reported in nine dystonia genes, namely DYT-HPCA, DYT-ANO3, DYT-KCTD17, DYT-THAP1, DYT-PRKRA, DYT-GNAL, DYT-TOR1A, DYT-KMT2B, and DYT-SGCE in the descending order of its frequency. HPCA gene mutation is rare, but all reported patients had tremor. Similarly, tremor was reported in eight genes associated with dystonia parkinsonism, namely DYT-SLC6A3, DYT-TH, DYT-SPR, DYT-PTS, DYT-GCH1, DYT-TAF1, DYT-QDPR, and DYT-SCL30A10 in the descending order of its prevalence. DYT-HPCA and DYT-ANO3 gene showed the highest prevalence of tremor in isolated dystonia, and DYT-SLC6A3 has the highest prevalence of tremor in combined dystonia.

Expanding the canvas of PRKN mutations in familial and early-onset Parkinson disease.

BACKGROUND: Mutations in PRKN (PARK2) are commonly encountered in early-onset Parkinson disease (PD). OBJECTIVES: To screen for PRKN mutations in a clinically well-characterized cohort of early-onset PD patients with a family history (FEOPD; ≤50 years at onset) or sporadic (SEOPD; ≤50 years at onset) and late-onset familial patients (FLOPD; >50 years at onset). METHODS: A total of 97 patients including 52 SEOPD and 45 familial PD (FEOPD: 23; FLOPD: 22) were screened for variants in PRKN by PCR- Sanger sequencing. PRKN dosage and variants in known PD genes were screened by qPCR and whole-exome sequencing in a subset of samples. RESULTS: A total of 25 (25.77%) patients (SEOPD: 12, FEOPD: 6, and FLOPD: 7) were positive for PRKN variants. Of these, two patients manifested homozygous variants; while one patient was carrying three PRKN variants and two patients were carrying two PRKN variants. But, we could not examine their parents or relatives and their genotypes remain unknown. The remaining 20 (80%) patients were carrying heterozygous variants only. 32% of these variants were in exon 2, including a novel truncating homozygous variant (c.97C > T:p.Arg33Ter) in a SEOPD patient. CONCLUSION: In our cohort, a novel homozygous variant (c.97C > T:p.Arg33Ter) in a patient with hyperhidrosis expands the spectrum of PRKN associated mutations. Furthermore, ~80% of the PRKN variants being heterozygous in this study cohort, implies the utility of the cohort for identification of additional novel/known causative PD gene(s).