Dominantly inherited essential tremor was recognized by Dana (1887). It may be the most common human movement disorder. The main feature of essential tremor is postural tremor of the arms, but the head, legs, trunk, voice, jaw, and ... Dominantly inherited essential tremor was recognized by Dana (1887). It may be the most common human movement disorder. The main feature of essential tremor is postural tremor of the arms, but the head, legs, trunk, voice, jaw, and facial muscles also may be involved. Aggravated by emotions, hunger, fatigue, and temperature extremes, the condition may cause a functional disability or even incapacitation. Beta-adrenergic blocking agents and primidone, established treatments for the disorder, are only partially effective and have significant side effects. Autosomal dominant inheritance can be demonstrated in most families. Deng et al. (2007) provided a detailed review of the genetics of essential tremor. - Genetic Heterogeneity of Essential Tremor Other mapped loci for hereditary essential tremor include ETM2 (602134) on chromosome 2p25-p22 and ETM3 (611456) on chromosome 6p23. ETM4 (614782) is caused by mutation in the FUS gene (137070) on chromosome 16p11.
Louis (2001) reviewed the clinical features of essential tremor and therapeutic options.
Critchley (1949) gave a classic review of this subject. Larsson and Sjogren (1960) did a thorough study of hereditary essential tremor in a parish ... Louis (2001) reviewed the clinical features of essential tremor and therapeutic options. Critchley (1949) gave a classic review of this subject. Larsson and Sjogren (1960) did a thorough study of hereditary essential tremor in a parish of Sweden. In all, 210 cases were ascertained. The age of onset, which showed high intrafamilial correlation, was on the average about 50 years and somewhat later in women than in men. 'Anticipation' (progressively earlier age of onset in successive generations) was not observed. Fine rapid tremor of the hands was usually the first symptom. Tremor of the arms, tongue (with dysarthria), head, legs, and trunk developed later, usually in the order listed. Mild extrapyramidal symptoms in the form of rigidity and stiffness of gait occurred frequently, but the clinical picture was easily distinguishable from parkinsonism (see 168600). Mental deterioration was not a feature. With 2 exceptions, all 210 cases could be traced back to 4 ancestral couples. The inheritance was autosomal dominant. From observation of about 15 presumed homozygous individuals, it was concluded that there is no difference from the disease in heterozygotes. It was estimated that more than 9% of the males and 6 to 6.5% of females of the parish carry the gene for essential tremor. The authors could find no reason to suspect selective fertility, selective mortality, or assortative mating as factors in the high gene frequency observed. Rather, chance variations that occurred when the population was small--about 150 persons in the late 1700s--seem to have been responsible. Kehrer (1965) described a family in which members of 3 successive generations had tremor of the hands and face and in 2 patients studied in detail, cerebral atrophy demonstrable by pneumoencephalography. He suggested that this represents a distinct entity. Busenbark et al. (1991) reported the results of a self-administered questionnaire concerning sickness-related dysfunction in 753 patients with essential tremor and compared the results with those in 87 controls and 145 patients with Parkinson disease. They concluded that although the disability with essential tremor is significant and may cause relatively greater psychosocial dysfunction, it tends to be less severe than in parkinsonism. Garcia-Albea et al. (1993) reported a 24-year-old man with paroxysmal episodes of tremor lasting from 10 to 60 minutes and occurring once every 3 to 6 weeks without apparent precipitating factors. The episodes were accompanied by a 9- to 10-Hz tremor electromyographically. A similar pattern was present in the patient's mother and in 2 of his 4 brothers. The authors proposed that this was a distinct variant. Bain and Findley (1994) believed that classic familial essential tremor typically begins with intermittent symptoms and that the observation of Garcia-Albea et al. (1993) should not be considered a novel variant. Bain et al. (1994) studied 93 first-degree relatives and 38 more distant relatives of 20 index patients with hereditary essential tremor. The age of onset was bimodally distributed with a median at 15 years, and penetrance was virtually complete at the age of 65 years. Approximately 50% of the cases were alcohol responsive. In most families, alcohol responsiveness or its absence was a consistent feature, but in 20% there was heterogeneity of alcohol response within the family. Head tremor was invariably mild and in 75% of cases was of a 'no-no' type. There was no association with Parkinson disease or dystonia, although classical migraine (see 157300) occurred in 26% of cases and cosegregated with tremor. Gulcher et al. (1997) quoted Jankovic et al. (1995) as finding that the average life expectancy of essential tremor patients is greater than that of unaffected members of their families. However, the disorder has a significant effect on the lives of the persons involved. Essential tremor may not appear until after 65 years of age. Current treatments using beta blockers or primidone have only limited efficacy and frequently become ineffective as the disease progresses. The tremor usually begins between adolescence and 40 years of age. Farrer et al. (1999) studied a family that raised the question of whether postural tremor (essential tremor) can be an alternative phenotype of the same pathogenic mutation that causes Lewy body parkinsonism (168601). They investigated a large family with levodopa-responsive Lewy body parkinsonism in which the disease segregated as an apparent autosomal dominant trait. After performing a genome screen, they identified a chromosome 4p haplotype that segregated with the disorder; however, this haplotype also occurred in individuals in the pedigree who did not have clinical Lewy body parkinsonism but rather suffered from postural tremor, consistent with essential tremor. In a population-based study of cognitive function among 232 Spanish patients with essential tremor and 696 control individuals, Benito-Leon et al. (2006) found that patients with essential tremor scored lower than controls on most neuropsychologic tests and global cognitive performance tests. In addition, a complaint of forgetfulness was marginally more common among essential tremor patients.
In 23 of 30 unrelated French families, Lucotte et al. (2006) found significant association between hereditary essential tremor and a BalI polymorphism in the DRD3 gene (S9G; 126451.0001) on chromosome 3q13. Parametric linkage analysis and transmission disequilibrium testing ... In 23 of 30 unrelated French families, Lucotte et al. (2006) found significant association between hereditary essential tremor and a BalI polymorphism in the DRD3 gene (S9G; 126451.0001) on chromosome 3q13. Parametric linkage analysis and transmission disequilibrium testing also showed significant positive association between the polymorphism and essential tremor. Among probands, gly9 homozygotes had significantly younger age at onset and more severe symptoms compared to heterozygotes, suggesting a gene dosage effect. Lucotte et al. (2006) noted that the polymorphism occurs in the extracellular N terminus of the protein, which may increase dopamine affinity and efficacy. The authors hypothesized that essential tremor may result from a gain-of-function mechanism.
Rautakorpi et al. (1982) reported a remarkably high frequency of essential tremor in a Finnish population: 55.5% of persons over 40 years of age.
Benito-Leon et al. (2005) estimated an annual incidence of essential tremor of ... Rautakorpi et al. (1982) reported a remarkably high frequency of essential tremor in a Finnish population: 55.5% of persons over 40 years of age. Benito-Leon et al. (2005) estimated an annual incidence of essential tremor of 616 per 100,000 among Spanish individuals aged 65 years and older. Sixty-four (77.1%) of 83 incident cases were diagnosed only during a follow-up, suggesting that many patients may never seek medical attention. The prevalence and incidence of essential tremor did not differ between men and women.