Elderly-onset essential tremor is associated with dementia
Renato PMunhoz, Federal University of Parana, Trav. Lange, 225 / 1201, Curitiba PR Brazil 80240-170[email protected]
Helio G. Teive
Submitted August 28, 2006
We read with great interest the article by Benito-Leon et al [1]
concerning dementia in patients with essential tremor (ET). They found
that subjects with onset of ET after age 65 were significantly more likely
to be demented than controls, while tremor onset at or below age 65 was
not associated with dementia.
While the authors discuss peculiar patterns of Lewy body or AD-type
pathology as candidates for the pathologic basis underlying this
association, they did not mention the possibility that some of these
patients may in fact be carriers of the fragile X premutation (FXP). [2,3]
The fragile X syndrome with mental retardation and typical physical
stigmata results from the expansion of a CGG trinucleotide repeat in the
FMR1 gene. Normally, FMR1 has 6 to 40 CGG repeats, while the full mutation
results from expansions with more than 200 repeats. Those with
intermediate expansions are considered as carriers of the FXP which has
recently been reported to be associated with the fragile X-associated
tremor/ataxia syndrome (FXTAS), including cases misdiagnosed as ET. [2,4]
FXP carriers frequencies are estimated to be 1 per 260 females and 1 per
760 males with a penetrance to FXTAS close to 50% at the age of 60 and up
to 100% for individuals older than 80. [3] While cases have been reported
in both men and women, FXTAS is probably more frequent in male subjects
that present typically with onset in the 6th decade and including
additional executive cognitive deficits, variable degrees of peripheral
neuropathy and occasionally mild parkinsonism. [2-4]
Although relatively more cases of FXTAS have been found in men and
60.4% of the ET cases in the Benito-Leon et al study are female, we think
that some of these patients may be FXP carriers and FXTAS should be
included as an additional alternative possibility to account for this
interesting finding.
References
1. Benito-Leon J, Louis ED, Bermejo-Pareja F, Neurological Disorders
in Central Spain Study Group. Elderly-onset essential tremor is associated
with dementia. Neurology 2006;66:1500-1505.
2. Hagerman PJ, Hagerman RJ. The fragile-X premutation: a maturing
perspective. Am J Hum Genet 2004;74:805-816.
3. Jacquemont S, Hagerman RJ, Leehey MA, et al. Penetrance of the
fragile X-associated tremor/ataxia syndrome in a premutation carrier
population. JAMA 2004;291:460-469.
4. Leehey MA, Munhoz RP, Lang AE, et al. The fragile X premutation
presenting as essential tremor. Arch Neurol 2003;60:117-121.
Disclosure: The authors report no conflicts of interest.
We read with great interest the article by Benito-Leon et al [1] concerning dementia in patients with essential tremor (ET). They found that subjects with onset of ET after age 65 were significantly more likely to be demented than controls, while tremor onset at or below age 65 was not associated with dementia.
While the authors discuss peculiar patterns of Lewy body or AD-type pathology as candidates for the pathologic basis underlying this association, they did not mention the possibility that some of these patients may in fact be carriers of the fragile X premutation (FXP). [2,3] The fragile X syndrome with mental retardation and typical physical stigmata results from the expansion of a CGG trinucleotide repeat in the FMR1 gene. Normally, FMR1 has 6 to 40 CGG repeats, while the full mutation results from expansions with more than 200 repeats. Those with intermediate expansions are considered as carriers of the FXP which has recently been reported to be associated with the fragile X-associated tremor/ataxia syndrome (FXTAS), including cases misdiagnosed as ET. [2,4]
FXP carriers frequencies are estimated to be 1 per 260 females and 1 per 760 males with a penetrance to FXTAS close to 50% at the age of 60 and up to 100% for individuals older than 80. [3] While cases have been reported in both men and women, FXTAS is probably more frequent in male subjects that present typically with onset in the 6th decade and including additional executive cognitive deficits, variable degrees of peripheral neuropathy and occasionally mild parkinsonism. [2-4]
Although relatively more cases of FXTAS have been found in men and 60.4% of the ET cases in the Benito-Leon et al study are female, we think that some of these patients may be FXP carriers and FXTAS should be included as an additional alternative possibility to account for this interesting finding.
References
1. Benito-Leon J, Louis ED, Bermejo-Pareja F, Neurological Disorders in Central Spain Study Group. Elderly-onset essential tremor is associated with dementia. Neurology 2006;66:1500-1505.
2. Hagerman PJ, Hagerman RJ. The fragile-X premutation: a maturing perspective. Am J Hum Genet 2004;74:805-816.
3. Jacquemont S, Hagerman RJ, Leehey MA, et al. Penetrance of the fragile X-associated tremor/ataxia syndrome in a premutation carrier population. JAMA 2004;291:460-469.
4. Leehey MA, Munhoz RP, Lang AE, et al. The fragile X premutation presenting as essential tremor. Arch Neurol 2003;60:117-121.
Disclosure: The authors report no conflicts of interest.