Similar early clinical presentations in familial and non-familial frontotemporal dementia

BACKGROUND: It is unclear whether there are early clinical features that can distinguish between patients with familial and non-familial frontotemporal dementia (FTD). OBJECTIVE: To compare the clinical features of FTD cases who have tau gene mutations with those of cases with a family history of FTD but no tau gene mutation, and with sporadic cases with neither feature. METHODS AND RESULTS: Comparisons of the behavioural, cognitive, and motor features in 32 FTD patients (five positive for tau gene mutations, nine familial but tau negative, and 18 tau negative sporadic) showed that age of onset and duration to diagnosis did not differ between the groups. Apathy was not observed in tau mutation positive cases, and dysexecutive signs were more frequent in familial tau mutation negative cases. Memory deficits and behavioural changes were common in all groups. CONCLUSIONS: In comparison with other neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease, neither tau gene mutations nor strong familial associations confer earlier disease susceptibility.     

Sporadic and familial dementia with ubiquitin-positive tau-negative inclusions: clinical features of one histopathological abnormality underlying frontotemporal lobar degeneration

BACKGROUND: Frontotemporal lobar degeneration comprises a group of diseases with clinical presentations and underlying histopathologies that overlap. Familial disease occurs in up to 50% of frontotemporal lobar degeneration cases. One of several underlying histopathological abnormalities is of ubiquitin-positive tau-negative inclusions, similar to those in motor neuron disease. OBJECTIVE: To compare clinical features of familial and sporadic cases in this pathological subgroup. DESIGN AND PATIENTS: Case note review of dementia patients with ubiquitin-positive tau-negative inclusion pathological abnormalities proven by autopsy. SETTING: United Kingdom tertiary referral center. MAIN OUTCOME MEASURES: Analysis of clinical features. RESULTS: Eleven familial cases (autosomal dominant) and 18 sporadic cases were identified. Most familial case patients presented with behavioral disturbances similar to those seen in sporadic behavioral cases. Semantic dementia was only seen in sporadic cases. Atypical features occurred in a minority. Sporadic and familial behavioral cases showed no differences in age at onset or disease duration. Neuropsychological test results revealed frontal or temporal deficits in most, but unexpected early parietal deficits in 1. CONCLUSIONS: Behavioral features in familial and sporadic cases were similar, but semantic dementia only occurred in sporadic cases. Diagnostic confusion with Alzheimer disease and corticobasal degeneration occurred in some cases.     

Clinical observations on familial cluster headache

Cluster headache (CH) has traditionally been considered a sporadic disease. Recently, an Italian study pointed out a risk of developing CH in the affected patients' firstdegree relatives that was increased 39-fold compared with the general population. The aims of this study were to investigate any possible differences in mean age at onset, clinical features and lifestyle between familial and non-familial CH cases. Among all CH patients referred to the Parma Headache Centre (n=691), we considered those who reported at least a first-degree relative with a probable diagnosis of CH in their family histories (n=30). CH diagnosis in the relatives was confirmed for 19 of the 30 patients. Each one of the 19 "familial cases" was matched by sex and age at the first visit (within 2 years) to two CH patients who did not report any family history for CH. The male:female ratio was 1.4:1 in the familial cases. Mean age at onset was significantly lower in women with familial CH than in those with non-familial CH. The study did not show any significant differences in symptoms between the two CH groups, such as pain location, accompanying symptoms, duration and frequency of attacks, and active periods. Our study seems to suggest that genetic factors play a role in the female gender, affecting age at onset of headache without modifying the clinical features. Received: 15 December 2002 / Accepted: 22 February 2003 Correspondence to: P. Torelli     

The impact of familial loading on gender differences in age at onset of schizophrenia

To evaluate the impact of familial loading and gender on age at onset, 197 schizophrenic patients were investigated. Patients with familial loading had an earlier age at onset without gender differences. In contrast, an earlier age at onset for men was found in sporadic cases. These data support that both gender and familial loading contribute to the heterogeneity of schizophrenia.     

Comparison of sporadic and familial disease amongst 580 cases of motor neuron disease.

A review of 580 hospital case notes of patients with motor neuron disease (MND) revealed 20 families in which more than one case had been reported. For 27 of the cases in these families full medical records were available, and a history of a further 37 affected family members were obtained. The cases in these 20 families are termed familial and the remainder sporadic. Parent to child transmission occurred in 16 of the 20 families of the familial cases, suggesting autosomal dominant inheritance. In three families there was involvement of siblings only, and in one family two cousins were affected. The sex ratio for the documented familial case records seen was 0.8:1 (M/F = 12:15), for the total (documented and historical) it was 1.06:1 (33:31), but in sporadic cases it was 1.6:1 (341:212) and more frequent occurrence of sensory features at presentation was reported in the familial cases (15% in the familial cases and 5% in the sporadic cases). However, none of these differences reached statistical significance. Familial cases also differed from sporadic cases in having a younger age of onset (a mean of 52 years in the familial cases compared with 56 years in the sporadic) and in the shorter median reported duration of illness (1.1 year in the familial cases; 2.6 years in the sporadic). However, in only one fifth of sporadic cases was the age at onset and death known, although this was known for 22 of the 27 familial cases, so that the data on survival and age of onset are too incomplete to test formally.     

Frontotemporal dementia: patient characteristics,cognition, and behaviour

OBJECTIVES: To describe sociodemographic data of patients with frontotemporal dementia (FTD), to compare the cognitive profile of patients with FTD with that of severity-matched patients with Alzheimer's disease using the CERAD neuropsychological battery (CERAD-NP), to investigate the frequency of behavioural disturbances, and to examine the relation between FTD-specific non-cognitive behavioural symptoms of patients with FTD with age and sex. METHODS: Fifty outpatients were diagnosed with FTD according to the Lund-Manchester consensus criteria. Cognitive impairment was assessed in 30 patients using the CERAD-NP. Severity of dementia was rated on the Clinical Dementia Rating (CDR). Eleven non-cognitive symptoms were rated by severity. To compare CERAD-NP results between patients with FTD and AD, 30 patients with AD were matched for age, sex, and global severity of cognitive performance. RESULTS: The average age at onset of first symptoms was 57.8 years. Eighteen patients (36%) had a positive family history of dementia. On the CERAD-NP patients with FTD performed significantly better than patients with AD on word list learning, delayed verbal recall and visuoconstruction (p < 0.05). There were no significant differences between FTD and AD on naming and verbal fluency tasks. The most frequent non-cognitive behavioural symptoms in FTD were loss of insight, speech abnormality, and apathy. Non-cognitive behavioural symptoms were more frequent in younger and in male than in older patients and in female patients. CONCLUSIONS: The CERAD-NP is a valuable clinical instrument for the cognitive evaluation of patients with suspected FTD. Complementary short tests of attention and executive function may be recommended. To enhance diagnostic sensitivity informant interviews should focus on non-cognitive behavioural changes, taking advantage of standardised questionnaires.     

Early-onset familial Alzheimer's disease (EOFAD)

Early-onset familial Alzheimer's disease (EOFAD) is a condition characterized by early onset dementia (age at onset < 65 years) and a positive family history for dementia. To date, 230 mutations in presenilin (PS1, PS2) and amyloid precursor protein (APP) genes have been identified in EOFAD. The mutations within these three genes (PS1/PS2/APP) affect a common pathogenic pathway in APP synthesis and proteolysis, which lead to excessive production of amyloid β. Compared with sporadic Alzheimer's disease (AD), EOFAD has some distinctive features including early age at onset, positive familial history, a variety of non-cognitive neurological symptoms and signs, and a more aggressive course. There is marked phenotypic heterogeneity among different mutations of EOFAD. Studies in presymptomatic mutation carriers reveal biomarkers abnormalities. EOFAD diagnosis is based on clinical and family history, neurological symptoms and examination, biomarker features, as well as genotyping in some cases. New therapeutic agents targeting amyloid formation may benefit EOFAD individuals.     

Apolipoprotein E ϵ4 allele is not associated with earlier age at onset in amyotrophic lateral sclerosis

Apolipoprotein E allele 4 (apo E ?4) is known to be in genetic disequilibrium with Alzheimer's disease and is associated with an earlier age at onset of dementia. Whether apo E ?4 is a specific risk factor for Alzheimer's disease or is a more general susceptibility factor that shifts the age at onset of neurodegenerative diseases to earlier ages is unknown. To test these possibilities, we determined the apolipoprotein E genotypes of subjects with familial or sporadic amyotrophic lateral sclerosis (ALS). ApoE allele frequencies of the the apoE gene of the ALS subjects (n = 170, ?2 = 0.071, ?3 = 0.771, ?4 = 0.159) were found to be comparable to the allele frequencies of the general population. Furthermore, no significant association was observed between the age at onset or the duration of ALS and the inheritance of apoE ?4: subjects with at least one copy of ?4 (sporadic ALS: n = 15, onset at 57.7 ± 13.9 years; familial ALS: n = 23, onset at 53.6 ± 9.5 years, duration [n = 14] of 2.6 ± 1.6 years) had comparable ages at onset and durations to subjects without ?4 (sporadic ALS: n = 28, onset at 53.1 ± 17.0 years; familial ALS: n = 56, onset at 50.8 ± 12.1 years, duration [n = 30] of 1.9 ± 0.8 years). The lack of association of apoE ?4 with the age at onset and the duration of ALS suggests that apoE ?4 does not have a global effect on the pathogenesis of other neurodegenerative diseases.     

A clinicopathological study on 13 cases of motor neuron disease with dementia]

Thirteen patients suffering from motor neuron disease with dementia were studied to analyze the clinicopathological spectrum. The diagnosis of the disease was made on the basis of a clinical history of progressive dementia and motor neuron involvement. The mean age at onset of 11 sporadic cases was 54.9 years (range, 43 to 69 years), with a mean duration of disease of 25 months (range, 11 to 47 months). The initial symptoms were dementia in 7 cases, motor neuron involvement in 2 cases, and both dementia and motor neuron involvement in 2 cases. The clinical picture of motor neuron disturbance in sporadic cases represented bulbar-type of amyotrophic lateral sclerosis (ALS). Bulbar palsy was the initial symptom in 7 sporadic cases and all 11 patients developed bulbar palsy with advancing course of illness. Muscular wasting and fasciculation were more predominant in the upper limbs, shoulder girdle and anterior chest. Fasciculation was more extensively and frequently observed in those portions than that of classical ALS. In contrast, muscle strength in the lower limbs was well preserved so that all patients could walk even when respiratory failure developed. Hyperreflexia including jaw jerk was found in all cases and positive Babinski sign in 7 cases. Parkinsonism appeared in the initial stage in one sporadic case and in two familial cases. The type of dementia with uninhibited behavior and personality change closely mimicked that of Pick's disease. The degree of dementia was mild or moderate in 8 cases and severe in 3 cases. Language disorder was characterized by progressive reduction of speech output, leading finally to mutism in 5 cases. Perseveration was observed in 10 cases. Visuospatial disorder was absent even in the advanced stage. Mild memory disturbance was noted in the early stage in 10 cases. Pathological examination was performed in 7 cases including one familial case, revealing frontal atrophy in 3 cases, frontotemporal atrophy in 2 cases and temporal atrophy in 2 cases. On microscopic examination there were mild neuronal loss, gliosis, mild spongy state of the cortical superficial layers and fibrous gliosis in the frontotemporal white matter. The scattered senile plaques in one case did not justify a diagnosis of Alzheimer's type dementia. Neither circumscribed atrophy nor Pick body was found in any case. The nucleus basalis of Meynert showed no neuronal loss. The substantia nigra showed a mild to severe loss of nerve cells without Lewy bodies in all cases.(ABSTRACT TRUNCATED AT 400 WORDS)     

TDP-43 pathological changes in early onset familial and sporadic Alzheimer��s disease, late onset Alzheimer��s disease and Down��s Syndrome: association with age, hippocampal sclerosis and clinical phenotype

TDP-43 immunoreactive (TDP-43-ir) pathological changes were investigated in the temporal cortex and hippocampus of 11 patients with autosomal dominant familial forms of Alzheimer's disease (FAD), 169 patients with sporadic AD [85 with early onset disease (EOAD) (i.e before 65 years of age), and 84 with late onset after this age (LOAD)], 50 individuals with Down's Syndrome (DS) and 5 patients with primary hippocampal sclerosis (HS). TDP-43-ir pathological changes were present, overall, in 34/180 of AD cases. They were present in 1/11 (9%) FAD, and 9/85 (10%) EOAD patients but were significantly more common (p = 0.003) in LOAD where 24/84 (29%) patients showed such changes. There were no demographic differences, other than onset age, between AD patients with or without TDP-43-ir pathological changes. Double immunolabelling indicated that these TDP-43-ir inclusions were frequently ubiquitinated, but were only rarely AT8 (tau) immunoreactive. Only 3 elderly DS individuals and 4/5 cases of primary HS showed similar changes. Overall, 21.7% of AD cases and 6% DS cases showed hippocampal sclerosis (HS). However, only 9% FAD cases and 16% EOAD cases showed HS, but 29% LOAD cases showed HS. The proportion of EOAD cases with both TDP-43 pathology and HS tended to be greater than those in LOAD, where nearly half of all the cases with TDP-43 pathology did not show HS. The presence of TDP-43-ir changes in AD and DS may therefore be a secondary phenomenon, relating more to ageing than to AD itself. Nevertheless, a challenge to such an interpretation comes from the finding in AD of a strong relationship between TDP-43 pathology and cognitive phenotype. Patients with TDP-43 pathology were significantly more likely to present with an amnestic syndrome than those without (p < 0.0001), in keeping with pathological changes in medial temporal lobe structures. HS was also associated more commonly with an amnestic presentation (p < 0.005), but this association disappeared when TDP-43-positive cases were excluded from the analysis. TDP-43 may, after all, be integral to the pathology of AD, and to some extent determine the clinical phenotype present.     

Neuronal intranuclear inclusions distinguish familial FTD-MND type from sporadic cases

Ubiquitin-immunoreactive (ub-ir) neuronal cytoplasmic inclusions are characteristically found in the extramotor cortex in patients with motor neuron disease and dementia (MND-dementia) and a subset of patients with frontotemporal dementia without motor symptoms (FTD-MND type). Recently, ub-ir neuronal intranuclear inclusions have been described in a small number of patients with familial FTD-MND type. To better define the sensitivity and specificity of this pathological change, we examined postmortem tissue from 14 patients with FTD-MND type (8 familial, 6 sporadic), 10 cases of MND-dementia (5 familial, 5 sporadic), and 19 cases of MND with no history of cognitive dysfunction (2 familial, 17 sporadic). Numerous intranuclear inclusions were found in multiple anatomic sites in 6/8 cases of familial FTD-MND. Rare intranuclear inclusions were present in the hippocampal dentate granule cells in 1 case of familial MND-dementia. No sporadic cases had intranuclear inclusions. These findings suggest that intranuclear inclusions are specific for familial FTD and may identify a subset of families with a common molecular pathogenesis. Although intranuclear inclusions are most characteristic of families in which the clinical presentation is pure FTD, they may also be found in some pedigrees with both FTD and MND; further supporting the hypothesis that FTD-MND type and MND-dementia represent a clinicopathological spectrum of disease.     

Analysis of familial and sporadic restless legs syndrome in age of onset,gender, and severity features

Abstract Restless Legs Syndrome is characterized by the irresistible, often indescribable unpleasant urge to move the limbs while resting. It has an estimated prevalence of ~29.3 % in US private practice. Restless Legs Syndrome often has a familial component; whether the familial and non-familial forms differ in terms of clinical features has previously been investigated, with the only significant factor emerging as younger age at onset in familial cases. Our study further explores a possible underlying difference between familial and sporadic forms of RLS by comparing familial RLS with sporadic RLS in terms of demographic and clinical features including subject gender, age of onset, and severity measures based an the IRLSSG severity scale. Both gender and family history are significant predictors of onset age in an overall model and also significant when analyzed independently. Participants who reported more severe RLS symptoms were significantly younger in age and progressed more rapidly. Two variables from the IRLSSG severity scale were significantly associated with age of onset when tested independently: discomfort and the urge to move the limb for relief. Our analysis supports the prevailing hypothesis that RLS is divided into earlier onset disease with a clear genetic component and later onset disease wich unclear etiology, and that one or more endophenotypes might exist within the disorder which could further characterize these subjects for future genetic studies.     

Clinical Aspects of Familial Forms of Frontotemporal Dementia Associated with Parkinsonism

Frontotemporal dementia is the second most common dementia among people under the age of 65. Fifty percent of affected patients have an associated family history. Several pathogenic genes have been identified for frontotemporal dementia associated with parkinsonism, including microtubule-associated protein tau, progranulin, and chromatin modifying protein 2B, and fused in sarcoma. It has also been reported that frontotemporal dementia associated with parkinsonism can be linked to chromosome 9p. In addition, there are families with frontotemporal dementia associated with a parkinsonian phenotype but unknown genetic status. Some of these kindreds have been diagnosed clinically as familial progressive supranuclear palsy, hereditary diffuse leukoencephalopathy with axonal spheroids, “overlap” syndrome, and others. Clinical presentation of frontotemporal dementia associated with parkinsonism is variable at age of symptomatic disease onset, disease duration, symptoms, and their occurrence during the disease course. Clinically, it is often difficult to sort out the different genetic forms of frontotemporal dementia associated with parkinsonism. However, with available clinical genetic testing for known genes, the precise diagnosis can be accomplished in some cases.     

Clinical characteristics of familial and sporadic Creutzfeldt-Jakob disease in Finland

The clinical features of 44 Finnish patients with Creutzfeldt-Jakob disease (CJD) were analyzed with special emphasis on the differences between the sporadic and familial forms. The 32 sporadic patients comprised all neuropathologically verified cases of CJD in 1974–89 in Finland. The 12 familial patients were members of the same pedigree where CJD has been linked with a mutation at codon 178 of the PRNP gene. The median age at the onset of the disease was 62.5 years and median duration 4.5 months in sporadic patients, and 49 years and 20.5 months in familial CJD, respectively. 90 percent of both sporadic and familial patients had myoclonus. Typical periodic EEG change was seen in 72% of sporadic patients, whereas the familial patients showed only a progressive slowing of EEG.     

The inheritance of Alzheimer's disease: a new interpretation

Ninety-one families of Alzheimer patients were studied to determine the proportion of familial cases, to obtain pedigrees for the analysis of the mode of inheritance, and to look for clinical differences between the familial and the nonfamilial cases. The diagnosis was confirmed by autopsy in 26 cases. Thirty-nine cases (43%) were familial, which is defined as more than one case in the family. Our interpretation of the pedigree data is that Alzheimer's disease is etiologically heterogeneous: it may be genetic or sporadic. In the familial type we think that the disease is inherited as an autosomal dominant, with a wide range of age of onset within a family. In one-third of these families the gene is not expressed until over age 70. No clinical differences were found between the familial and the sporadic groups.     

Dementia in Parkinson's disease: a post-mortem study in a population of brain donors

OBJECTIVE: To identify factors associated with dementia in a cohort of Parkinson's disease (PD) brain donors and determine whether its presence may influence the clinical phenotype of the disease. METHODS: We included 67 consecutive patients with a clinical and pathological diagnosis of PD, who while alive, consented to donate their brains to the University of Miami Brain Endowment Bank(TM). Dementia and psychiatric complications of PD were diagnosed according to established criteria. Case histories were abstracted and reviewed and comparisons between PD patients with (PD-D, n = 34) and without (PD, n = 33) dementia were made. RESULTS: Age at death, age at disease onset and disease duration did not differ significantly between PD-D and PD patients. Other symptoms were similar in both groups. Visual hallucinations and bilateral symptoms at diagnosis were significantly higher in PD-D patients. No association between dementia and overall survival duration was found. Although the frequency of depression and psychosis was higher in the PD patients with dementia no statistical significance was reached. The overall lifetime prevalence of dementia in our group was 50.7%. CONCLUSIONS: Visual hallucinations and bilateral symptoms were associated with dementia in our cohort of PD brain donors. No association between dementia and survival duration was found. Understanding the influence of dementia on the clinical phenotype of the disease and predicting its development is essential for the successful management of PD.     

Clinical profiles and ethnic heterogeneity of sporadic fatal insomnia

Background and purpose

This study was undertaken to elucidate the clinical profile of sporadic fatal insomnia (sFI), assess the similarities and differences between sFI and fatal familial insomnia (FFI), and evaluate the influence of ethnicity on the phenotype of sFI patients.

Methods

The data of sFI and FFI patients were retrieved from our case series and through literature review. The clinical and diagnostic features of sFI and FFI were compared, as were the phenotypes of Asian and Caucasian sFI patients.

Results

We identified 44 sFI and 157 FFI cases. The prevalence of sleep-related, neuropsychiatric, and autonomic symptoms among the sFI patients were 65.9%, 100.0%, and 43.2%, respectively. Compared to FFI, sFI exhibited longer disease duration and a higher proportion of neuropsychiatric symptoms, whereas FFI was characterized by a higher incidence of sleep-related and autonomic symptoms in the early stages of the disease or throughout its course. In addition, a higher proportion of the sFI patients showed hyperintensity on magnetic resonance imaging (MRI) and periodic sharp wave complexes on electroencephalography compared to the FFI patients, especially those presenting with pathological changes associated with MM2-cortical type sporadic Creutzfeldt–Jakob disease. The Asian sFI patients had a higher proportion of males and positivity for cerebrospinal fluid 14-3-3 protein, and fewer sleep-related symptoms compared to Caucasian sFI patients. The age at onset and duration of sFI differed between ethnic groups, but the difference failed to reach statistical significance.

Conclusions

Despite its similarities to FFI, sFI is characterized by longer disease duration, higher proportion of neuropsychiatric symptoms, and hyperintensity on MRI, along with differences in the clinical characteristics based on ethnicity.     

Clinical characteristics of familial versus sporadic alcoholism in a sample of male and female patients.

Presence of a family history of alcoholism may predict clinical characteristics in affected subjects, such as an earlier age at onset. More frequent and severe social maladjustment and somatic complications are also regularly cited for familial alcoholism, although subject to many other confusing factors. We analysed the clinical specificities of 79 alcohol-dependent inpatients according to the absence versus presence of family history of alcoholism. Patients were evaluated for lifetime psychiatric morbidity with the Diagnostic Interview for Genetic Studies (DIGS), for somatic complications with a systematic screening list, and first-degree relatives (N = 428) were assessed with the Family Inventory Schedule and Criteria (FISC). Age at onset and social complications were predicting familial versus sporadic alcoholism, even when considering censored data and/or interaction between variables. But differences became non-significant when excluding patients with antisocial personality. If age at onset effectively appears to be the most informative characteristic for predicting familial versus sporadic alcoholism, it seems that it may be necessary in future studies to systematically take into account antisocial personality diagnosis, because of a probable contamination.     

Anticipation of age at onset in familial multiple sclerosis

Background and objective: Anticipation of age at onset in the younger generations is a widely known characteristic of many diseases with genetic inheritance. This study was performed to assess whether there is anticipation of age at onset in younger generations of familial multiple sclerosis (MS) in a Spanish population and to compare clinical characteristics of familial and sporadic MS. Methods: We studied a cohort of 1110 patients diagnosed with MS and followed‐up in our MS Unit. Patients were considered as familial MS if they had in their family at least one relative of first or second degree diagnosed with MS. Otherwise, patients were considered to have sporadic MS. We compared the age at onset between relatives from different generations, and we also compared the age at onset of familial and sporadic MS. Results: A lower age at onset in the younger generations was found (median 22 years vs. 30 years, P < 0.001) and a significant lower age at onset of the disease in familial MS comparing to sporadic MS (median 25 years vs. 29 years, P = 0.042). Conclusions: There is an anticipation of the age at onset of MS in the younger generations of patients with familial MS. There is also a lower age at onset in familial versus sporadic MS.     

The impact of familial structure on Parkinson's disease in Istanbul Medical School, Turkey

The prevalence and family structure of idiopathic Parkinson disease (iPD) in Turkey is not known. Patients with iPD were recruited consecutively at the Medical School of Istanbul University over an 18-month period. Clinical details were assessed with standardized forms. Of the 219 iPD patients, 136 had sporadic iPD [26 with parental consanguinity (cs)], 20 autosomal recessive PD (9 with cs) and 63 autosomal dominant or pseudo-dominant inheritances (20 with cs). Age at onset was 49.1 ± 17.1 years (range 3-83) and age at examination 56.4 ± 16.5 years (range 4-93). Ages at examination and at clinical onset of PD were significantly greater in sporadic iPD than in familial iPD patients, but disease duration was similar. Patients with familial PD had significantly lower basal UPDRS III and Hoehn and Yahr scores than sporadic PD patients and brisk reflexes in the lower limbs were significantly more frequent, but they suffered less from mictional problems. The frequency of familial PD and consanguinity in Turkey is higher and age at onset of iPD earlier than in Western countries. Molecular diagnoses and genetic counseling will therefore have a very important impact on the medical, psychological, and familial handling of PD in Turkey.