Introduction: The national protocol of genetic counselling and pre-symptomatic testing for late-o... more Introduction: The national protocol of genetic counselling and pre-symptomatic testing for late-onset neurological diseases began in Portugal in 1995. Initially, it was accessible only to adults at-risk for Machado-Joseph disease, but was later extended to other hereditary ataxias, to Huntington’s disease and to familial amyloid polyneuropathy caused by Val30Met mutation at the transthyretin gene. The aim of this study was to describe the profile of the population seeking pre-symptomatic testing, while also reflecting on the experience of conducting the protocol of multidisciplinary sessions since 1996.Material and Methods: We conducted a retrospective study and collected data from clinical records of consultands who requested pre-symptomatic testing at our centre in Porto (Portugal) during the first twenty years of practice (1996 - 2015).Results: A total of 1446 records were reviewed. The most common reason for testing was to reduce uncertainty (41.7%). The rate of withdrawals befo...
This study addresses the profile of at-risk subjects whose long-term psychological impact of pres... more This study addresses the profile of at-risk subjects whose long-term psychological impact of presymptomatic testing (PST) for Familial Amyloid Polyneuropathy (FAP) TTR V30M is negative. The sample consisted of 177 subjects, aged over 20 years that were 50% at-risk for FAP, and performed the PST at least three years ago. Participants were contacted by mail, one time only, to answer the sociodemographic questionnaire and the Brief Symptom Inventory (BSI), the Self-Rating Anxiety Scale of Zung (SAS), and the Beck Depression Inventory (BDI). From the sample, 22.6% (BSI), 16.4% (SAS), and 9% (BDI) subjects presented negative psychological impact, after having performed the PST for more than 3 years. Subjects with clinically significant values in BSI, SAS, and BDI have an overlapping profile concerning the total sample, except regarding age, since clinically depressed subjects have a higher mean age. Married women or living in unmarried unions, aged between 30 and 45 years, employed, carr...
European Journal of Medical Genetics, Mar 23, 2018
This longitudinal study aimed at determining predicting variables for middle and long-term psycho... more This longitudinal study aimed at determining predicting variables for middle and long-term psychological disturbance due pre-symptomatic testing (PST) for two late-onset neurological diseases, Huntington disease (HD) and TTR (transthyretin protein) familial amyloid polyneuropathy (FAP) Val30Met (now classified as Val50Met). We analysed 196 clinical records of persons who performed PST at least three years ago and answered to the two stages of evaluation (before PST and least 3 years after disclosure of results). For this purpose, regression analysis was performed, showing that the Positive Symptom Distress Index (PSDI), psychoticism, somatization and paranoid ideation dimensions assume predictive value in the middle and long-term impact for total anxiety and PSDI. The result of PST was not a relevant predictor. Application of an evaluation instrument of various psychopathological dimensions played a fundamental role in the detection of clinical situations that may arise several year...
Background. Over the past 20 years, studies have revealed that the communication of a pre-symptom... more Background. Over the past 20 years, studies have revealed that the communication of a pre-symptomatic test (PST) result for autosomal dominant late-onset diseases, such as Huntington's disease (HD), doesn’t cause psychological disturbance. This cross-sectional study investigated the middle- (4 years) to long-term (7 and 10 years) psychological impact in individuals who agreed to perform the pre-symptomatic testing for 3 autosomal dominant late-onset diseases: HD, Machado-Joseph disease (MJD) and familial amyloid polyneuropathy (FAP). Method: The study included 203 subjects: 170 (84%) agreed to make the PST for FAP, 29 (14%) for HD and 4 (2%) for MJD. Subjects were mostly women (58%) and married (67%). Three cutoffs points were considered: 4 years (middle-term) and 7 and 10 years (long-term) indicating the time after receiving the PST results. Results: results showed that women and widows (oldest) participants presented the highest mean values for almost all BSI dimensions and th...
This cross-sectional study investigated depression as the middle- (4 years) and long-term (7 and ... more This cross-sectional study investigated depression as the middle- (4 years) and long-term (7 and 10 years) psychological impact of pre-symptomatic testing (PST) for 3 autosomal dominant late-onset diseases: Huntington’s disease (HD), Machado-Joseph disease (MJD) and familial amyloidotic polyneuropathy (FAP) TTR V30M. It included 203 subjects: 170 (83.7%) underwent the PST for FAP, 29 (14.3%) for HD and 4 (2%) for MJD. Of these 203, 73 were still asymptomatic carriers, 29 (14.5%) were symptomatic, 9 (4.5%) were FAP liver transplanted patients and 89 (44.5%) were non-carriers. Subjects were mainly women (58.1%) and married (66.5%). The Beck Depression Inventory (BDI) was used to evaluate depression. Scores were higher for symptomatic carriers and for those who have made one or more psychological support consultations over the years. For the formers, the mean scores pointed to mild depression. Asymptomatic carriers and non-carriers had similar scores but it was impossible to differenti...
Objective: To study anxiety as a variable of middle- and long-term psy-chological impact of pre-s... more Objective: To study anxiety as a variable of middle- and long-term psy-chological impact of pre-symptomatic testing (PST) for 3 autosomal dominant late-onset disorders: Huntington's disease (HD), Machado-Joseph disease (MJD) and familial amyloid polyneuropathy (FAP) TTR V30M. This topic addresses specific and significant knowledge to the Portuguese consultant population. Methods: This cross-sectional study included 203 participants: 170 (83.7%) underwent the PST for FAP, 29 (14.3%) for HD and 4 (2%) for MJD. Of the 203 participants, 73 (36.0%) were asymptomatic carriers, 29 (14.5%) were symptomatic carriers, 9 (4.5%) were FAP patients who have had a liver transplant and 89 (44.5%) were non-carrier; they were mostly women (58.1%) and married (66.5%). The anxiety variable was assessed using the Zung Self-Rating Anxiety Scale (SAS). Results: The anxiety scores were higher for the symptomatic carriers and for those who underwent psychological support consultations over the years; fo...
The psychological impact of pre-symptomatic testing for some late-onset diseases is still an impo... more The psychological impact of pre-symptomatic testing for some late-onset diseases is still an important topic of study, particularly in the Portuguese population, since there are not many studies published in this field. In a retrospective study, we have investigated the psychological impact, concerning depression indicators, of pre-symptomatic testing (PST) for 3 autosomal dominant late-onset diseases: Huntington disease (HD), Machado-Joseph disease (MJD) and familial amyloidotic polyneuropathy (FAP) ATTRV30M. The study included 686 subjects: 586 (85.4%) were at-risk for FAP ATTRV30M, 92 (13.4%) for HD and 8 (1.2%) for MJD. Among all, 352 received a mutation-carrier result, and 305 a non-carrier result. The majority were women (58.6%). Mean age was 36.3 years (SD, 11,8). Most (50.9%) were single, while 44.5% were married or living with a partner. The Beck Depression Inventory (BDI) was completed before testing and againthree weeks, six months and one year after results. Depression scores decreased significantly during the post-testing period, although carriers showed higher values than non-carriers.
Machado-Joseph disease [MJD, also spinocerebellar ataxia type 3 (SCA3)] and familial amyloid poly... more Machado-Joseph disease [MJD, also spinocerebellar ataxia type 3 (SCA3)] and familial amyloid polyneuropathy type I (FAP-I or ATTR V30M) are neurodegenerative disorders, inherited in an autosomal dominant fashion, which have a high prevalence in Portugal, probably due to a founder effect. MJD and FAP-I are late-onset diseases, with symptoms emerging usually during adulthood. CGPP, which is the national reference centre for these disorders, has a genetic lab that offers diagnostic, pre-symptomatic and prenatal testing and an outpatient clinic to counsel and follow relatives at risk for hereditary ataxias, FAP-I and Huntington disease (HD). The present work is a review of our 10-year experience with psychological counselling of individuals at risk for MJD and FAP-I. Persons at risk for FAP-I may show a better response to pre-symptomatic testing than those who are at risk for MJD and HD because of the availability of liver transplantation, which may improve their health and life expecta...
In this retrospective study, we have researched the psychological impact of pre-symptomatic testi... more In this retrospective study, we have researched the psychological impact of pre-symptomatic testing (PST) for 2 autosomal dominant late-onset diseases: Huntington disease (HD and familial amyloidotic polyneuropathy (FAP) V30M TTR. The study included 53 subjects: 40 (75.5%) were the offspring at risk for FAP and 13 (24.5%) for HD. Of these, 38 (73.1%) received the carrier result and 12 (23.1%) the noncarrier result; 3 of them did not want to know the result. The indicators taken for emotional distress were the subscales and global indexes of psychopathological Behavior Symptoms Inventory (BSI), applied in the pre-test and post-test, one-year after notification of results. Values decreased significantly one year after the implementation of the PST, regardless of the studied disease or test result; this seems to corroborate previous studies showing that testing does not increase pre-symptomatic levels of emotional disturbance in individuals. However, the subjects studied showed, for all subscales and global indexes of the BSI, significantly higher values than those of control groups.
MJD is the most frequent dominant ataxia and an incapacitating disorder. Onset is most frequently... more MJD is the most frequent dominant ataxia and an incapacitating disorder. Onset is most frequently during the reproductive years, and genetic counseling is its only means of prevention. The causative mutation--an expansion of a (CAG)n on chromosome 14q32.1--can now be directly detected. We now report the first two cases of prenatal diagnosis (PND). The first presented as a simultaneous request for predictive testing and PND at 14 weeks of pregnancy. Owing to time constraints, we performed a full protocol of counseling with shorter inter between sessions, while psycho-social evaluation of the other parent obstetric consults were also begun. We ensured that the couple wished termination if the fetus was a carrier, to avoid a presymptomatic test for the unborn child. We were thus able to deliver test results two weeks before PND. As the fetus carried an expanded allele (77 CAGs) inherited from his father, termination was performed and the couple received counselling, psychological and social support. The second case was the fetus of a carrier-mother that was diagnosed as non-carrier, also after amniocentesis.
The psychological impact of pre-symptomatic testing for some late-onset diseases is still an impo... more The psychological impact of pre-symptomatic testing for some late-onset diseases is still an important topic of study, particularly in the Portuguese population, since there are not many studies published in this field. In a retrospective study, we have investigated the psychological impact, concerning depression indicators, of pre-symptomatic testing (PST) for 3 autosomal dominant late-onset diseases: Huntington disease (HD), Machado-Joseph disease (MJD) and familial amyloidotic polyneuropathy (FAP) ATTRV30M. The study included 686 subjects: 586 (85.4%) were at-risk for FAP ATTRV30M, 92 (13.4%) for HD and 8 (1.2%) for MJD. Among all, 352 received a mutation-carrier result, and 305 a non-carrier result. The majority were women (58.6%). Mean age was 36.3 years (SD, 11,8). Most (50.9%) were single, while 44.5% were married or living with a partner.
In this retrospective study we have investigated the anxiety as an impact of pre-symptomatic test... more In this retrospective study we have investigated the anxiety as an impact of pre-symptomatic testing (PST) for 3 autosomal dominant late-onset diseases: Hunt-ington disease (HD), Machado-Joseph disease (MJD) and familial amyloidotic polyneuropathy (FAP) V30M TTR. The study included 686 subjects: 586 (85.4%) were the offspring at risk for FAP, 92 (13.4%) for HD and 8 (1.2%) to MJD. Of these, 352 received the car-rier result and 305 the non-carrier result. As indica-tor of anxiety distress was taken the Self-Rating An-xiety Scale of Zung (SAS), applied in the pre-test and the three post-test moments: three weeks, 6 months and one year after notification of test results. Values decreased significantly along the four evaluation mo-ments, regardless the studied disease or test result. For female population, SAS means cores revealed results of clinical anxiety at pre-test, only decreasing to non clinical scores a year after PST disclosure.
Introduction: The national protocol of genetic counselling and pre-symptomatic testing for late-o... more Introduction: The national protocol of genetic counselling and pre-symptomatic testing for late-onset neurological diseases began in Portugal in 1995. Initially, it was accessible only to adults at-risk for Machado-Joseph disease, but was later extended to other hereditary ataxias, to Huntington’s disease and to familial amyloid polyneuropathy caused by Val30Met mutation at the transthyretin gene. The aim of this study was to describe the profile of the population seeking pre-symptomatic testing, while also reflecting on the experience of conducting the protocol of multidisciplinary sessions since 1996.Material and Methods: We conducted a retrospective study and collected data from clinical records of consultands who requested pre-symptomatic testing at our centre in Porto (Portugal) during the first twenty years of practice (1996 - 2015).Results: A total of 1446 records were reviewed. The most common reason for testing was to reduce uncertainty (41.7%). The rate of withdrawals befo...
This study addresses the profile of at-risk subjects whose long-term psychological impact of pres... more This study addresses the profile of at-risk subjects whose long-term psychological impact of presymptomatic testing (PST) for Familial Amyloid Polyneuropathy (FAP) TTR V30M is negative. The sample consisted of 177 subjects, aged over 20 years that were 50% at-risk for FAP, and performed the PST at least three years ago. Participants were contacted by mail, one time only, to answer the sociodemographic questionnaire and the Brief Symptom Inventory (BSI), the Self-Rating Anxiety Scale of Zung (SAS), and the Beck Depression Inventory (BDI). From the sample, 22.6% (BSI), 16.4% (SAS), and 9% (BDI) subjects presented negative psychological impact, after having performed the PST for more than 3 years. Subjects with clinically significant values in BSI, SAS, and BDI have an overlapping profile concerning the total sample, except regarding age, since clinically depressed subjects have a higher mean age. Married women or living in unmarried unions, aged between 30 and 45 years, employed, carr...
European Journal of Medical Genetics, Mar 23, 2018
This longitudinal study aimed at determining predicting variables for middle and long-term psycho... more This longitudinal study aimed at determining predicting variables for middle and long-term psychological disturbance due pre-symptomatic testing (PST) for two late-onset neurological diseases, Huntington disease (HD) and TTR (transthyretin protein) familial amyloid polyneuropathy (FAP) Val30Met (now classified as Val50Met). We analysed 196 clinical records of persons who performed PST at least three years ago and answered to the two stages of evaluation (before PST and least 3 years after disclosure of results). For this purpose, regression analysis was performed, showing that the Positive Symptom Distress Index (PSDI), psychoticism, somatization and paranoid ideation dimensions assume predictive value in the middle and long-term impact for total anxiety and PSDI. The result of PST was not a relevant predictor. Application of an evaluation instrument of various psychopathological dimensions played a fundamental role in the detection of clinical situations that may arise several year...
Background. Over the past 20 years, studies have revealed that the communication of a pre-symptom... more Background. Over the past 20 years, studies have revealed that the communication of a pre-symptomatic test (PST) result for autosomal dominant late-onset diseases, such as Huntington's disease (HD), doesn’t cause psychological disturbance. This cross-sectional study investigated the middle- (4 years) to long-term (7 and 10 years) psychological impact in individuals who agreed to perform the pre-symptomatic testing for 3 autosomal dominant late-onset diseases: HD, Machado-Joseph disease (MJD) and familial amyloid polyneuropathy (FAP). Method: The study included 203 subjects: 170 (84%) agreed to make the PST for FAP, 29 (14%) for HD and 4 (2%) for MJD. Subjects were mostly women (58%) and married (67%). Three cutoffs points were considered: 4 years (middle-term) and 7 and 10 years (long-term) indicating the time after receiving the PST results. Results: results showed that women and widows (oldest) participants presented the highest mean values for almost all BSI dimensions and th...
This cross-sectional study investigated depression as the middle- (4 years) and long-term (7 and ... more This cross-sectional study investigated depression as the middle- (4 years) and long-term (7 and 10 years) psychological impact of pre-symptomatic testing (PST) for 3 autosomal dominant late-onset diseases: Huntington’s disease (HD), Machado-Joseph disease (MJD) and familial amyloidotic polyneuropathy (FAP) TTR V30M. It included 203 subjects: 170 (83.7%) underwent the PST for FAP, 29 (14.3%) for HD and 4 (2%) for MJD. Of these 203, 73 were still asymptomatic carriers, 29 (14.5%) were symptomatic, 9 (4.5%) were FAP liver transplanted patients and 89 (44.5%) were non-carriers. Subjects were mainly women (58.1%) and married (66.5%). The Beck Depression Inventory (BDI) was used to evaluate depression. Scores were higher for symptomatic carriers and for those who have made one or more psychological support consultations over the years. For the formers, the mean scores pointed to mild depression. Asymptomatic carriers and non-carriers had similar scores but it was impossible to differenti...
Objective: To study anxiety as a variable of middle- and long-term psy-chological impact of pre-s... more Objective: To study anxiety as a variable of middle- and long-term psy-chological impact of pre-symptomatic testing (PST) for 3 autosomal dominant late-onset disorders: Huntington's disease (HD), Machado-Joseph disease (MJD) and familial amyloid polyneuropathy (FAP) TTR V30M. This topic addresses specific and significant knowledge to the Portuguese consultant population. Methods: This cross-sectional study included 203 participants: 170 (83.7%) underwent the PST for FAP, 29 (14.3%) for HD and 4 (2%) for MJD. Of the 203 participants, 73 (36.0%) were asymptomatic carriers, 29 (14.5%) were symptomatic carriers, 9 (4.5%) were FAP patients who have had a liver transplant and 89 (44.5%) were non-carrier; they were mostly women (58.1%) and married (66.5%). The anxiety variable was assessed using the Zung Self-Rating Anxiety Scale (SAS). Results: The anxiety scores were higher for the symptomatic carriers and for those who underwent psychological support consultations over the years; fo...
The psychological impact of pre-symptomatic testing for some late-onset diseases is still an impo... more The psychological impact of pre-symptomatic testing for some late-onset diseases is still an important topic of study, particularly in the Portuguese population, since there are not many studies published in this field. In a retrospective study, we have investigated the psychological impact, concerning depression indicators, of pre-symptomatic testing (PST) for 3 autosomal dominant late-onset diseases: Huntington disease (HD), Machado-Joseph disease (MJD) and familial amyloidotic polyneuropathy (FAP) ATTRV30M. The study included 686 subjects: 586 (85.4%) were at-risk for FAP ATTRV30M, 92 (13.4%) for HD and 8 (1.2%) for MJD. Among all, 352 received a mutation-carrier result, and 305 a non-carrier result. The majority were women (58.6%). Mean age was 36.3 years (SD, 11,8). Most (50.9%) were single, while 44.5% were married or living with a partner. The Beck Depression Inventory (BDI) was completed before testing and againthree weeks, six months and one year after results. Depression scores decreased significantly during the post-testing period, although carriers showed higher values than non-carriers.
Machado-Joseph disease [MJD, also spinocerebellar ataxia type 3 (SCA3)] and familial amyloid poly... more Machado-Joseph disease [MJD, also spinocerebellar ataxia type 3 (SCA3)] and familial amyloid polyneuropathy type I (FAP-I or ATTR V30M) are neurodegenerative disorders, inherited in an autosomal dominant fashion, which have a high prevalence in Portugal, probably due to a founder effect. MJD and FAP-I are late-onset diseases, with symptoms emerging usually during adulthood. CGPP, which is the national reference centre for these disorders, has a genetic lab that offers diagnostic, pre-symptomatic and prenatal testing and an outpatient clinic to counsel and follow relatives at risk for hereditary ataxias, FAP-I and Huntington disease (HD). The present work is a review of our 10-year experience with psychological counselling of individuals at risk for MJD and FAP-I. Persons at risk for FAP-I may show a better response to pre-symptomatic testing than those who are at risk for MJD and HD because of the availability of liver transplantation, which may improve their health and life expecta...
In this retrospective study, we have researched the psychological impact of pre-symptomatic testi... more In this retrospective study, we have researched the psychological impact of pre-symptomatic testing (PST) for 2 autosomal dominant late-onset diseases: Huntington disease (HD and familial amyloidotic polyneuropathy (FAP) V30M TTR. The study included 53 subjects: 40 (75.5%) were the offspring at risk for FAP and 13 (24.5%) for HD. Of these, 38 (73.1%) received the carrier result and 12 (23.1%) the noncarrier result; 3 of them did not want to know the result. The indicators taken for emotional distress were the subscales and global indexes of psychopathological Behavior Symptoms Inventory (BSI), applied in the pre-test and post-test, one-year after notification of results. Values decreased significantly one year after the implementation of the PST, regardless of the studied disease or test result; this seems to corroborate previous studies showing that testing does not increase pre-symptomatic levels of emotional disturbance in individuals. However, the subjects studied showed, for all subscales and global indexes of the BSI, significantly higher values than those of control groups.
MJD is the most frequent dominant ataxia and an incapacitating disorder. Onset is most frequently... more MJD is the most frequent dominant ataxia and an incapacitating disorder. Onset is most frequently during the reproductive years, and genetic counseling is its only means of prevention. The causative mutation--an expansion of a (CAG)n on chromosome 14q32.1--can now be directly detected. We now report the first two cases of prenatal diagnosis (PND). The first presented as a simultaneous request for predictive testing and PND at 14 weeks of pregnancy. Owing to time constraints, we performed a full protocol of counseling with shorter inter between sessions, while psycho-social evaluation of the other parent obstetric consults were also begun. We ensured that the couple wished termination if the fetus was a carrier, to avoid a presymptomatic test for the unborn child. We were thus able to deliver test results two weeks before PND. As the fetus carried an expanded allele (77 CAGs) inherited from his father, termination was performed and the couple received counselling, psychological and social support. The second case was the fetus of a carrier-mother that was diagnosed as non-carrier, also after amniocentesis.
The psychological impact of pre-symptomatic testing for some late-onset diseases is still an impo... more The psychological impact of pre-symptomatic testing for some late-onset diseases is still an important topic of study, particularly in the Portuguese population, since there are not many studies published in this field. In a retrospective study, we have investigated the psychological impact, concerning depression indicators, of pre-symptomatic testing (PST) for 3 autosomal dominant late-onset diseases: Huntington disease (HD), Machado-Joseph disease (MJD) and familial amyloidotic polyneuropathy (FAP) ATTRV30M. The study included 686 subjects: 586 (85.4%) were at-risk for FAP ATTRV30M, 92 (13.4%) for HD and 8 (1.2%) for MJD. Among all, 352 received a mutation-carrier result, and 305 a non-carrier result. The majority were women (58.6%). Mean age was 36.3 years (SD, 11,8). Most (50.9%) were single, while 44.5% were married or living with a partner.
In this retrospective study we have investigated the anxiety as an impact of pre-symptomatic test... more In this retrospective study we have investigated the anxiety as an impact of pre-symptomatic testing (PST) for 3 autosomal dominant late-onset diseases: Hunt-ington disease (HD), Machado-Joseph disease (MJD) and familial amyloidotic polyneuropathy (FAP) V30M TTR. The study included 686 subjects: 586 (85.4%) were the offspring at risk for FAP, 92 (13.4%) for HD and 8 (1.2%) to MJD. Of these, 352 received the car-rier result and 305 the non-carrier result. As indica-tor of anxiety distress was taken the Self-Rating An-xiety Scale of Zung (SAS), applied in the pre-test and the three post-test moments: three weeks, 6 months and one year after notification of test results. Values decreased significantly along the four evaluation mo-ments, regardless the studied disease or test result. For female population, SAS means cores revealed results of clinical anxiety at pre-test, only decreasing to non clinical scores a year after PST disclosure.
Uploads
Papers by susana ledo