“Familial Parkinson's Disease” – A Case-Control Study of Families

ABSTRACT:Background:Parkinson's disease (PD) patients frequently report a family history of PD and this may provide etiological clues to PD. It has also been suggested that a report of a negative family history is reliable. We studied the prevalence of PD in relatives of PD patients to assess the reliability of family history and to evaluate possible explanations of “familial PD”(fPD).Methods:81 of 650 (12.5%) PD probands (all PD patients seen at clinic in 4 years) reported a positive family history of PD. Each fPD proband was matched with non-familial PD (nfPD) proband by gender and year of birth. Screening and follow-up questionnaires were mailed to relatives to obtain information concerning pedigree and presence of neurodegenerative disease. Available family members (regardless of disease status) were examined.Results:On examination, 8 persons, said to be “normal” by probands, relatives and themselves, had definite or possible PD (5 fPD, 3 nfPD). The prevalence rate of PD among first and second degree living relatives of probands varied significantly between fPD and nfPD groups (6269/100 000 versus 1190/100 000; p < 0.001). The weighted prevalence (taking into account the proportions of fPD and nfPD within the clinic) was 1822/100 000, a value more than 5 times higher than reported prevalence rates of PD in the general population (p < 0.001). The prevalence rate was greater in first degree relatives than second degree.Conclusions:“Familial parkinsonism” cannot be explained merely by size of or advanced age within families. Significant numbers of previously unrecognized PD patients may be identified despite a “negative” family history. That is, the patient's report of an absence of familial parkinsonism is frequently inaccurate. The prevalence rate in relatives of PD patients appears to be higher than the general population – regardless of the family history reported by a PD patient. We believe our study suggests that genetic influences or early life environmental exposures are likely to be of etiological importance in PD.

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Parkinson’s disease determinants, prediction and gene–environment interactions in the UK Biobank

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2020-323646 ◽

2020 ◽

Vol 91 (10) ◽

pp. 1046-1054 ◽

Cited By ~ 2

Author(s):

Benjamin Meir Jacobs ◽

Daniel Belete ◽

Jonathan Bestwick ◽

Cornelis Blauwendraat ◽

Sara Bandres-Ciga ◽

...

Keyword(s):

Risk Factors ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Family History ◽

Genetic Risk ◽

Positive Family History ◽

Risk Scores ◽

Uk Biobank ◽

Gene Environment ◽

History Of

ObjectiveTo systematically investigate the association of environmental risk factors and prodromal features with incident Parkinson’s disease (PD) diagnosis and the interaction of genetic risk with these factors. To evaluate whether existing risk prediction algorithms are improved by the inclusion of genetic risk scores.MethodsWe identified individuals with an incident diagnosis of PD (n=1276) and controls (n=500 406) in UK Biobank. We determined the association of risk factors with incident PD using adjusted logistic regression models. We constructed polygenic risk scores (PRSs) using external weights and selected the best PRS from a subset of the cohort (30%). The PRS was used in a separate testing set (70%) to examine gene–environment interactions and compare predictive models for PD.ResultsStrong evidence of association (false discovery rate <0.05) was found between PD and a positive family history of PD, a positive family history of dementia, non-smoking, low alcohol consumption, depression, daytime somnolence, epilepsy and earlier menarche. Individuals with the highest 10% of PRSs had increased risk of PD (OR 3.37, 95% CI 2.41 to 4.70) compared with the lowest risk decile. A higher PRS was associated with earlier age at PD diagnosis and inclusion of the PRS in the PREDICT-PD algorithm led to a modest improvement in model performance. We found evidence of an interaction between the PRS and diabetes.InterpretationHere, we used UK Biobank data to reproduce several well-known associations with PD, to demonstrate the validity of a PRS and to demonstrate a novel gene–environment interaction, whereby the effect of diabetes on PD risk appears to depend on background genetic risk for PD.

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Positive family history of essential tremor influences the motor phenotype of Parkinson's disease

Movement Disorders ◽

10.1002/mds.22772 ◽

2009 ◽

Vol 24 (15) ◽

pp. 2285-2288 ◽

Cited By ~ 8

Author(s):

Peter Hedera ◽

John Y. Fang ◽

Fenna Phibbs ◽

Michael K. Cooper ◽

P. David Charles ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Family History ◽

Essential Tremor ◽

Positive Family History ◽

History Of ◽

Motor Phenotype

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Family history based approach in risk prediction for Parkinson's disease: Additional contribution of familial associated disorders

Genetika ◽

10.2298/gensr1501303v ◽

2015 ◽

Vol 47 (1) ◽

pp. 303-310

Author(s):

Irena Vrecar ◽

Ales Maver ◽

Zvezdan Pirtosek ◽

Dejan Georgiev ◽

Zalika Klemenc-Ketis ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Family History ◽

Risk Prediction ◽

Positive Family History ◽

Caffeine Intake ◽

Additional Contribution ◽

Risk Models ◽

Predictive Capacity ◽

History Of

The aim of our study was to examine the contribution of family history of Parkinson's disease and its associated disorders in the assessment of predictive capacity of risk models for Parkinson?s disease. In a population of 192 patients with Parkinson?s disease and 1659 healthy individuals we investigated the impact of environmental factors and the effects of family history on Parkinson's disease risk. Pesticides exposure, positive family history of Parkinson?s disease and a positive family history of dementia and melanoma were associated to an increased risk for Parkinson?s disease, with results regarding family history of depression near to statistical significance. Smoking and caffeine intake were associated to a decreased risk for Parkinson?s disease. Three risk prediction models were assessed using the area under the curve approach: first model was based on known environmental risk factors, in the second model we added family history of Parkinson?s disease and in the third model we additionally included family history of dementia, melanoma and depression. We showed that inclusion of data on family history of associated disorders (AUC 0.76) improves predictive capacity of risk model for Parkinson?s disease in comparison with the first (AUC 0.62) and the second model (AUC 0.71). We concluded that family history of associated disorders: dementia, depression and melanoma improves predictive capacity of risk models for Parkinson?s disease.

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Parkinson's Disease: A Genetic Study

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100036362 ◽

1986 ◽

Vol 13 (3) ◽

pp. 248-251 ◽

Cited By ~ 36

Author(s):

Ma. Elisa Alonso ◽

Enrique Otero ◽

Rosalinda D'Regules ◽

Hector Hugo Figueroa

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Family History ◽

Genetic Study ◽

Early Onset ◽

Positive Family History ◽

Genetic Load ◽

Control Group ◽

The Family ◽

History Of

ABSTRACT:A sample of 122 patients with Parkinson's Disease was studied for the purpose of investigating if the frequency of relatives affected with Parkinson in this group was higher than in a control group and to see if the genetic load was more important in some of the subtypes of Parkinson described by Barbeau and Pourcher (1982).7 In our 122 patients, we found that 1.7% were post-encephalic parkinsonian, 12.3% were symptomatic cases and 86% of the idiopathic variety. There were 16.1% early onset patients in the idiopathic group and among these we found 23.5% with a positive family history of Parkinson in the first-degree relatives. In 6 cases with the tremor onset form of the disease, the family history was positive and 5 patients, 4.7% had familial essential tremor-related Parkinsonism. Our results support Barbeau's hypothesis7.19 that Parkinson is a heterogeneous disease in which some subtypes (such as early onset Parkinson) have an important genetic subceptibility component.

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Hunting for Familial Parkinson’s Disease Mutations in the Post Genome Era

Genes ◽

10.3390/genes12030430 ◽

2021 ◽

Vol 12 (3) ◽

pp. 430

Author(s):

Steven R. Bentley ◽

Ilaria Guella ◽

Holly E. Sherman ◽

Hannah M. Neuendorf ◽

Alex M. Sykes ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Family History ◽

Rare Variants ◽

Strong Family History ◽

Disease Mutations ◽

Whole Exome ◽

History Of ◽

Functional Consequences ◽

Multiplex Families

Parkinson’s disease (PD) is typically sporadic; however, multi-incident families provide a powerful platform to discover novel genetic forms of disease. Their identification supports deciphering molecular processes leading to disease and may inform of new therapeutic targets. The LRRK2 p.G2019S mutation causes PD in 42.5–68% of carriers by the age of 80 years. We hypothesise similarly intermediately penetrant mutations may present in multi-incident families with a generally strong family history of disease. We have analysed six multiplex families for missense variants using whole exome sequencing to find 32 rare heterozygous mutations shared amongst affected members. Included in these mutations was the KCNJ15 p.R28C variant, identified in five affected members of the same family, two elderly unaffected members of the same family, and two unrelated PD cases. Additionally, the SIPA1L1 p.R236Q variant was identified in three related affected members and an unrelated familial case. While the evidence presented here is not sufficient to assign causality to these rare variants, it does provide novel candidates for hypothesis testing in other modestly sized families with a strong family history. Future analysis will include characterisation of functional consequences and assessment of carriers in other familial cases.

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Family history of hand tremor in patients with early Parkinson’s disease

Journal of Clinical Neuroscience ◽

10.1016/j.jocn.2021.05.041 ◽

2021 ◽

Vol 90 ◽

pp. 161-164

Author(s):

Seong-Min Choi ◽

Soo Hyun Cho ◽

Kyung Wook Kang ◽

Jae-Myung Kim ◽

Byeong C. Kim

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Family History ◽

Hand Tremor ◽

History Of ◽

Early Parkinson’S Disease

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Kinetics of Ca2(+)-ATPase activation in platelet membranes of essential hypertensives and normotensives

AJP Cell Physiology ◽

10.1152/ajpcell.1990.258.6.c988 ◽

1990 ◽

Vol 258 (6) ◽

pp. C988-C994 ◽

Cited By ~ 20

Author(s):

J. Takaya ◽

N. Lasker ◽

R. Bamforth ◽

M. Gutkin ◽

L. H. Byrd ◽

...

Keyword(s):

Essential Hypertension ◽

Family History ◽

Positive Family History ◽

Plasma Renin ◽

Initial Reaction ◽

Activation Kinetics ◽

Negative Family History ◽

History Of ◽

Blacks And Whites ◽

Kinetics Of

To explore the etiology of altered Ca metabolism in essential hypertension, we studied parameters, i.e., maximal initial reaction velocity (Vmax) and Michaelis constant (Km), of Ca activation kinetics of Ca2(+)-ATPase in membrane fractions (isolated by a sucrose gradient) from platelets of blacks and whites, 27 of whom were essential hypertensives, 17 of whom were normotensives with a family history of essential hypertension, and 10 of whom were normotensives without a family history of the disease. The Vmax of hypertensives was significantly lower than in normotensives without a family history of essential hypertension (hypertensives, 14.99 +/- 1.71 nmol Pi.mg protein-1.min-1; normotensives, positive family history, 22.67 +/- 3.17 nmol Pi.mg protein-1.min-1; normotensives, negative family history, 27.54 +/- 4.37 nmol Pi.mg protein-1.min-1; overall, P = 0.0078). The Km was lower in both hypertensives and normotensives with a positive family history of essential hypertension as compared with normotensives with a negative family history of the disease (hypertensives, 1.70 +/- 0.23 microM; normotensives, positive family history, 1.38 +/- 0.2 microM; normotensives, negative family history, 2.79 +/- 0.58 microM; overall, P = 0.0251). Furthermore, the Km in whites was inversely related to plasma renin activity (r = 0.50; P less than 0.005). We propose that a lower Vmax for Ca2(+)-ATPase may play a role in the higher level of free Ca in platelets of essential hypertensives and that a higher affinity of the enzyme to Ca may reflect a process compensating for the lower Vmax. We also suggest that a higher Km for Ca2(+)-ATPase in juxtaglomerular cells of whites would result in blunting the release of renin.

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Hereditary Spherocytosis in a 22 Month Old Child

TAJ Journal of Teachers Association ◽

10.3329/taj.v30i2.39143 ◽

2018 ◽

Vol 30 (2) ◽

pp. 79-82

Author(s):

Mst Musarrat Sultana ◽

Md Shafiqul Islam ◽

Md Sanaul Haque Mia

Keyword(s):

Family History ◽

Hereditary Spherocytosis ◽

Positive Family History ◽

Osmotic Fragility ◽

Blood Film ◽

College Hospital ◽

Negative Family History ◽

Medical College ◽

Antiglobulin Test ◽

History Of

Hereditary spherocytosis (HS) is a familial hemolytic disorder with marked heterogeneity of clinical features, ranging from asymptomatic condition to a fulminant hemolytic anemia. Although a positive family history of spherocytosis increases the risk for this disorder, it may be sporadic in some case. A 22-month old girl was admitted in Rajshahi Medical College Hospital with pallor and jaundice. Her parents gave history of repeated episodes of pallor and jaundice since 8 month of age with negative family history. Blood film showed plenty of spherocytes, reticulocytosis of 15.0%, negative direct antiglobulin test& positive osmotic fragility test. She was managed conservatively on nutritional supplements& one unit of blood transfusion. To the best of our knowledge, this is the first reported case of hereditary spherocytosis from Rajshahi Medical College Hospital.TAJ 2017; 30(2): 79-82

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Factors Influencing Development of Depressive Illness among Parkinson’s Disease Patients

Journal of National Institute of Neurosciences Bangladesh ◽

10.3329/jninb.v5i2.43013 ◽

2019 ◽

Vol 5 (2) ◽

pp. 106-110

Author(s):

Provat Kumar Sarkar ◽

Hasan Zahidur Rahman ◽

Mahua Chandra ◽

Anis Ahmed ◽

Md Enayet Ul Islam ◽

...

Keyword(s):

Diabetes Mellitus ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Family History ◽

Depression Scale ◽

Depressive Illness ◽

Age Group ◽

Cross Sectional ◽

History Of ◽

Axis I

Background: Depressive illness is present among Parkinson’s disease (PD) patients. Objective: The purpose of the present study was to see the influencing factors of development of depressive illness among Parkinson’s disease patients. Methodology: This comparative cross-sectional study was carried out in the Department of Neurology and Department of Psychiatry at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2009 to June 2011 for a period of two (2) years. Parkinson’s disease patients who were attended at the movement disorder clinic and general OPD of Department of Neurology and in-patient department of Neurology at BSMMU, Dhaka were selected as study population. Patients with Parkinson’s plus syndrome, with dementia or other causes of parkinsonism like vascular or drug induced parkinsonism were excluded from this study. Data were collected by filling structured clinical questionnaire, then filling up of ‘structured clinical interview for DSM-IV Axis I disorders’ (SCID-CV) and self-reported ‘Depression scale` questionnaire. Parkinson disease was diagnosed by neurologist by the presence of two or more of the four cardinal criteria namely tremor, rigidity, bradykinesia and postural instability. Then patients were screened for depression by a psychiatrist of Department of Psychiatry at BSMMU, Dhaka. Result: A total of 100 Parkinson’s disease patients were interviewed and 80 patients ultimately participated in the study. The mean age of total Parkinson’s disease patients was 57.71±12.36 years ranging from 35 to 82 years with highest percentage (35%) had age group 65 years or above, 28.7% in 55 to 64 years, 22.5% in 45 to 54 years and lowest percentage (13.8%) in age group less than 45 years. Among 80 Parkinson’s disease patients, depression was present in 34 (42%) patients and was absent in 46 (58%) patients. Diabetes mellitus (p=0.125), hypertension (p=0.097), hypothyroidism (p=1.000), other illness (p=0.595), family history of PD (p=0.758) and levodopa use (p=0.661) were not significantly associated with the development of depressive illness in Parkinson’s disease. Conclusion: Diabetes mellitus (DM), hypertension (HTN), hypothyroidism, other illness, family history of PD and levodopa use do not significantly influence in the development of depressive illness among the Parkinson’s disease. Journal of National Institute of Neurosciences Bangladesh, 2019;5(2): 106-110

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Genetic Insights into Early-onset Parkinson’s Disease

US Neurology ◽

10.17925/usn.2010.06.01.41 ◽

2010 ◽

Vol 06 (01) ◽

pp. 41

Author(s):

Roy N Alcalay ◽

Cheryl Waters ◽

◽

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Family History ◽

Early Onset ◽

Late Onset ◽

Positive Family History ◽

Disease Onset ◽

Leucine Rich Repeat ◽

Strong Family History ◽

Early Onset Parkinson’S Disease

Early-onset Parkinson’s disease (EOPD) is defined as disease onset before 40 or 50 years of age. The clinical characteristics of EOPD are very similar to those of late-onset PD, but dystonia is more often a presenting symptom, dementia is rare, and disease progression may be slower. Mutations in several genes have been described in cases with EOPD, often with strong family history, including mutations in α-synuclein (SNCA),DJ-1, PTEN-induced kinase-1 (PINK-1), andATP13A2. However, the most common mutations identified in EOPD are in Parkin (PRKN), leucine-rich repeat kinase 2 (LRRK2), and glucocerebrosidase (GBA). With the exception ofSNCAandATP13A2carriers, mutation carriers are often indistinguishable from non-carriers. Large series of EOPD cases that are not ascertained by family history estimate mutation frequency at 4–16%. Given that the frequency of positive family history is much higher, we believe that many genetic risk factors are yet to be discovered.

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