Orthostatic tremor in three brothers

Abstract

Sirs: Orthostatic tremor (OT) is a rare form of tremor that occurs usually in legs upon standing upright with a typical tremor frequency of 13–18 Hz (for review see references [1, 2]). We report OT in three elderly brothers (patients #1, 2, 3; 69, 68, 63 yrs, respectively) without a family history for OT or essential tremor (ET). They complained of unsteadiness upon standing due to quivering legs since the age of 59, 63 and 50, respectively. They had no leg tremor in positions other than standing, and no arm or head tremor ever occurred. Both patients #1 and #3 suffered from sleep bruxism. Some other family members were reported to also be afflicted by bruxism but not by OT (Fig. 1). There was no jaw tremor in any of the three brothers, confirmed by EMG recording in patient #1. The three brothers have lived in different environments beyond childhood and adolescence and were not exposed to environmental toxins. On examination they showed quivering of the leg muscles during standing that became stronger over time. Arm tremor was not present. No ataxia or gait disturbance was present. EMG recordings showed a 16–17 Hz tremor in the legs during standing and in the upper limbs during isometric contraction in all three patients (Fig. 2). A repetitive nerve stimulation test of the N. accessorius in patient #1 due to ocular and bulbar weakness showed a 19 % decrement at 3 Hz, typical of MG. Testing for antiacetylcholine receptor antibodies was positive while MuSK antibody titers were in the reference range. He had a benign thymoma. Thyroid antibodies were positive, but ANA, ENA and ANCA were negative. Besides tremor patient #2 complained of a hoarse voice for at least 10 years, Dupuytren’s contracture, Peyronie’s disease (induratio penis plastica) and minor lid drop on the right side that was stable for at least 30 years. Further neurological examination was normal for all three patients. Several characteristic features distinguish OT from ET: OT has a uniquely high frequency of 13–18 Hz. Two cases of a 16 and 14 Hz jaw tremor, respectively, without leg tremor are the only reported exceptions [3, 4]. OT is unresponsive to alcohol and β-blocker, only present during standing (or isometric muscle contraction) and usually has no family history of tremor. ET has a frequency of 6–8 Hz, is often familiar and is an action tremor usually of the upper limbs (pure leg tremor without upper limb tremor was observed in only 2.2 % of ET patients [1, 5]. But there is an ongoing debate whether OT might be a variant of ET [6–8]. For example, PET studies revealed hyperactivity of the cerebellum in both OT and ET [9, 10]. To determine whether OT segregated with known loci for ET, a linkage analysis in two identified susceptibility loci for ET on chromosomes 3q13 (ETM1) and 2p24.1 (ETM2) was performed for all three patients and additional family members (IV, 1–4; V, 4; see Fig. 1). DNA was isolated using standard procedures. The STR markers were chosen from GDB (http://www.gdb.org/gdb/) according to their localisation at the two loci ETM1 and ETM2 and typed as described [11]. The constructed haplotypes for both loci in the patients did not co-segregate with OT. There was also no linkage between the identified haplotypes and bruxism. Genetic factors for bruxism have been considered both in children and in adults [12]. But the co-occurrence of OT with bruxism might be incidental. A recent report about OT in monozygotic twins [13] and this report are arguments for a genetic basis of OT. Further genetic analysis has to be performed to clarify the genetic basis of OT and bruxism.