Discredited legacy: Stigma and familial amyloid polyneuropathy in Northwestern Portugal

Rationale Genetic inherited conditions may result in feelings of stigmatisation, mainly because of visible physical appearance and its transmissibility to offspring. Objective This article reports accounts of stigmatisation from Portuguese patients affected by the inherited neurodegenerative disease, familial amyloid polyneuropathy (FAP), living in the largest cluster of patients worldwide. Method We draw on semi-structured interviews conducted with individuals at-risk or affected by FAP, recruited through the national patients' association, about their experiences of stigmatisation related to the illness. Results Findings highlight the influence of a discrediting social context in the enactment of stigma. FAP was described as a source of devaluation and social distance and was permeated by beliefs of contagion in the community, especially in the past. The multigenerational nature of the illness within small communities was felt as a source of rejection for courtship and of devalued reproductive worth. Decisions to have (potentially affected) children seemed to be a target of implicit negative judgment. Dealing with stigma entailed restraint in talking about FAP especially outside the family, resistance to being treated as different, and social withdrawal. Some participants referred to recent substantial improvements in their social acceptance and a reduction in the intensity of the stigmatisation to which they are subject. Conclusion The pattern of stigma may have changed considerably within the past few decades, as medical information about the disease became more widespread, as new medications have been introduced and as clinical trials of other potential treatments have been established. Our findings report the social consequences of stigma towards this disease group and may help to understand how stigma is experienced in other heritable diseases

Risk perception in subjects at-risk for Familial Amyloidotic Polyneuropathy: Percepción del riesgo en sujetos con riesgo de Polineuropatía Amiloide Familiar

http://sherpa.ac.uk/romeo/issn/2011-2777/The aims of this study are to know if subjects at-risk were aware of their 50% risk for Familial Amyloidotic Polyneuropathy (FAP); to know the value of the subjective risk; to understand the association between sociodemographic characteristics and risk perception, and between the risk status and the subjective perception of risk. 174 subjects 50% atrisk for FAP were tested. 52.9% subjects at-risk were aware of their 50% risk condition. The mean value of the subjective risk was higher and closer to 50% when the subjects were aware of their 50% risk condition. Education was associated to a higher awareness of being at 50% risk. It seems that information on previous knowledge before performing the genetic counselling increases the subjective risk.Los objetivos de este estudio son saber si los sujetos en riesgo eran conscientes de su riesgo del 50% para la polineuropatía amiloide familiar (PAF); conocer el valor del riesgo subjetivo; y comprender la asociación entre las características sociodemográficas y la percepción del riesgo y entre el riesgo real y la percepción subjetiva del riesgo. Se examinaron 174 sujetos con riesgo de PAF del 50%. 52,9% de los sujetos en riesgo eran conscientes de su condición de riesgo del 50%. El valor medio del riesgo subjetivo fue mayor y más cercano al 50% cuando los sujetos eran conscientes de su condición de riesgo del 50%. La educación se asoció a una mayor conciencia de estar al 50% de riesgo. Parece que la información sobre los conocimientos previos antes de realizar el asesoramiento genético aumenta el riesgo subjetivo.info:eu-repo/semantics/publishedVersio

Motivation to perform presymptomatic testing in portuguese subjects at-risk for late-onset genetic diseases

http://sherpa.ac.uk/romeo/issn/1668-7027/The role of the clinical psychologist in the context of genetic counseling includes support for the process of decision-making for subjects at-risk, regardless of the decision that was made. For this, it is important to know the motivations behind these decisions. What may be considered advantageous and justifiable reasons to perform the PST for genetic diseases from the medical and public point of view, i.e., planning for the future, helping in the choice of a profession, family planning, improving quality of life and contributing to health, may not be recognized as such by the individual seeking the PST. This study addresses the motivation to perform the presymptomatic testing (PST) of subjects at-risk for 3 diseases, Familial Amyloid Polyneuropathy (FAP), Huntington's disease (HD) and Machado-Joseph disease (MJD), compared with the motivation to perform the PST for Hemochromatosis (HH). FAP, HD and MJD are three genetic (monogenic) autosomal dominant late-onset diseases (LONDs) with no cure. FAP is a progressive sensorimotor and autonomic neuropathy of adulthood. HD is characterized by a triad of clinical symptoms of chorea (motor, cognitive and psychiatric symptoms), emotional distress and cognitive decline. MJD is characterized by slowly progressive clumsiness in the arms and legs, a staggering lurching gait, sometimes mistaken for drunkenness, difficulty with speech and swallowing, involuntary eye movements, and may be accompanied by double vision or bulging eyes, and lower limb spasticity. HH is a disease in which too much iron accumulates in parenchymal organs, leading to iron overload and subsequent organ toxicity and failure. The study participants consisted in 213 subjects at genetic risk for FAP, HD and MJD and 31 subjects at genetic risk for HH, that were assessed through an interview to obtain sociodemographic data and the answer to one question about motivation to perform PST: “Which were the reasons that led you to perform the predictive test?" This study was carried out in Center for Predictive and Preventive Genetics (CGPP), Institute for Molecular and Cell Biology (IBMC), Porto, Portugal. This research used a mixed-method, since qualitative and quantitative techniques of data analysis were used. Before deciding to seek genetic counseling and to know their genetic status, subjects at-risk have naturally considered their motives and it was probably the pro-counseling reasons the ones dictating the motivation to perform the PST. This may suggest that in fact there is a prior self-selection to the test, i.e. only those considering to have emotional skills to go through the process, performing the test. Seven major categories were obtained. The most significant ones for FAP, HD and MJD were reasons related to the future, reasons related to others and reasons related to curiosity and to the need to know. For HH, the most important ones were reasons related to others and reasons related to the characteristics of the disease. The motivation of subjects at-risk to perform the PST for FAP, HD and MJD is external and unrelated to the disease, while the motivation of subjects at-risk to perform the PST for HH is related to the disease. Reasons related to others are a common motivation: as subjects at-risk for FAP, HD and MJD, subjects at-risk for HH also chose reasons related to others as one of the most important motivations to carry out the PST. These subjects also care about the fact that they can transmit the disease to their children and care about other family members which are already ill. The category reasons related to others includes subcategories that identify the person and the situation that led to the decision to perform a PST. Subjects at-risk are also concerned about the fact that they have to decide whether or not to have children and its economic implications.El papel del psicólogo clínico en el contexto del consejo genético incluye el apoyo al proceso de toma de decisiones para los sujetos en riesgo, independientemente de la cola se tomó la decisión. Este estudio aborda la motivación para realizar las pruebas pre-sintomáticas (PPS) de sujetos en situación de riesgo para tres enfermedades, polineuropatía amiloide familiar (PAF), la enfermedad de Huntington (EH) y la enfermedad de Machado-Joseph (EMJ) y comparar con la motivación para realizar la PPS para hemocromatosis (HH). La muestra consistió en 213 sujetos portugués que tenían riesgo genético para contraer las tres enfermedades y 31 sujetos en situación de riesgo genético para contraer la HH. Ellos fueron evaluados con una entrevista para obtener datos socio-demográficos y debían responder a una pregunta sobre la motivación para llevar a cabo las PPS. Se obtuvieron siete categorías principales. Las más significativas para PAF, EH y EMJ fueron razones relacionadas con el futuro, razones relacionadas con los demás y razones relacionadas con la curiosidad y la necesidad de conocer. Para HH, las más importantes fueron razones relacionadas con los demás y razones relacionadas con las características de la enfermedad. La motivación para realizar el PST de la PAF, EH y EMJ es externa y sin relación con la enfermedad, mientras que la motivación de los sujetos en situación de riesgo para la HH está relacionada con la enfermedad. Las razones relacionadas con los demás es una motivación común. Estos sujetos también se preocupan que pueden transmitir la enfermedad a sus hijos.info:eu-repo/semantics/publishedVersio

Depression as the Middle- and Long-Term Impact for Pre-Symptomatic Testing of Late-Onset Neurodegenerative Disorders: La Depresión como el Indicador de Impacto Psicológico a la Media y Largo Plazo de la Prueba Pre-Sintomática para Enfermedades de Aparición Tardía - A Depressão como Indicador do Impacto Psicológico a Médio e Longo Prazo do Teste Pré-Sintomático de Doenças Neurodegenerativas de Início Tardio

http://sherpa.ac.uk/romeo/search.php?issn=1413-389XThis 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 differentiate the psychological impact between the medium and long-term. For symptomatic carriers, there were significant differences between the middle- and long-term. The study indicates that depression occurs only when subjects had previously manifested the first symptoms of their neurologic disease.Este estudo transversal investigou a depressão como indicador do impacto psicológico do teste pré-sintomático (TPS) a médio (quatro anos) e longo prazo (de 7 a 10 anos) de doenças neurológicas de início tardio: a doença de Huntington (DH), doença de Machado-Joseph (DMJ) e polineuropatia amiloidótica familiar PAF (TTR V30M). 203 sujeitos participaram no estudo: 170 (83,7%) submetidos ao TPS para PAF, 29 (14,3%) para o DH e 4 (2%) para DMJ. Destes 203, 73 eram portadores assintomáticos, 29 (14,5%) já eram sintomáticos, 9 (4,5%) pacientes com PAF, já tinham realizado o transplante hepático e 89 (44,5%) eram não-portadores. A amostra era constituída maioritariamente por mulheres (58,1%) e por sujeitos casados (66,5%). Utilizou-se o Inventário da Depressão de Beck (BDI). Os scores mais elevados foram observados nos portadores sintomáticos e nos sujeitos que tinham realizado consultas de psicologia com scores indicadores de depressão leve. Os portadores assintomáticos e os não-portadores apresentaram médias semelhantes. Para os portadores sintomáticos, encontrámos diferenças signifi cativas entre o médio e o longo prazo. Este estudo conclui que a depressão pode ocorrer nos indivíduos que já manifestam os primeiros sintomas da respectiva doença neurológica.Este estudio transversal investigó la depresión a la media (4 años) y largo plazo (7 y 10 años) del impacto psicológico de la prueba pre-sintomática (PPS) para 3 enfermedades autosómicos, dominantes, de aparición tardía: la enfermedad de Huntington (EH), la enfermedad de Machado-Joseph (EMJ) y la polineuropatia amiloide familiare (PAF) o polineuropatia amiloide da transtiretina FAP (TTR V30M). Participaron 203 sujetos: 170 (83,7%) para PPS para PAF, 29 (14,3%) para EH y 4 (2%) para EMJ. De estos 203, 73 estaban todavía portador asintomático, 29 (14,5%) eran sintomáticos, 9 (4,5%) fueron PAF pacientes con trasplante hepático y 89 (44,5%) eran no-portadores. Eran en su mayoría mujeres (58,1%) y casados (66,5%). Se utilizó el Inventario de Depresión de Beck (IDB). Los puntajes fueron mayores para las portadoras sintomáticas y para aquellos que han hecho consultas de apoyo psicológico con puntuaciones medias de depresión leve. Los portadores asintomáticos y no portadores tuvieron puntajes similares. Para portadores sintomáticos, hubo diferencias signifi cativas entre el medio y largo plazo. Este estudio concluye que la depresión puede ocurrir en personas que ya muestran los primeros síntomas de la enfermedad neurológica.info:eu-repo/semantics/publishedVersio

Mid- and long-term anxiety levels associated with presymptomatic testing of Huntington's disease, Machado-Joseph disease, and familial amyloid polyneuropathy

http://sherpa.ac.uk/romeo/search.php?issn=1809-452XOBJECTIVE: To study anxiety as a variable of the mid- and long-term psychological impact of pre-symptomatic testing for three autosomal dominant late-onset disorders - Huntington's disease (HD), Machado-Joseph disease (MJD) and familial amyloid polyneuropathy (FAP) TTR V30M - in a Portuguese sample. METHODS: This cross-sectional study included 203 participants: 170 (83.7%) underwent pre-symptomatic testing 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 diagnosed with FAP and had a liver transplant, and 89 (44.5%) were non-carriers. Most were 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 symptomatic carriers and for those who underwent psychological support consultations over the years. For symptomatic carriers, the mean scores were superior to 40 points, which reflects clinical anxiety. CONCLUSION: Although it was not possible to differentiate between the mid- and long-term psychological impacts, this study supports the conclusion that the proximity to the age of symptoms onset might be a trigger for anxiety.info:eu-repo/semantics/publishedVersio

Pre-symptomatic testing for neurodegenerative disorders: Middle- to long-term psychopathological impact: Pruebas pre-sintomáticas de enfermedades neurodegenerativas: el impacto psicopatológico a largo plazo

http://sherpa.ac.uk/romeo/issn/0214-9915/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 the highest mean values correspond to the obsessive-compulsive BSI dimensions. Concerning the nature of the disease, MJD participants presented the highest mean values. No differences were found concerning the PST test results while participants are still asymptomatic. Psychopathology was only present in symptomatic carriers. Conclusions: The onset of the disease seems to assume the trigger for the presence of psychological disturbance in the subjects, regardless the time that has elapsed since the PST result communication or the individual carrier/non-carrier condition.Antecedentes: el presente estudio transversal investigó el impacto psicopatológico a medio (4 años) y a largo plazo (7 y 10 años) de la prueba pre-sintomática (PPS) para tres enfermedades autosómicas dominantes de aparición tardía: enfermedad de Huntington EH, la enfermedad de Machado-Joseph (EMJ) y la polineuropatía amiloide familiar (PAF). Método: participaron 203 sujetos: 170 (84 %) realizaron el PPS para PAF, 29 (14 %) para EH y 4 (2 %) para EMJ. La muestra, en su mayoría, estuvo compuesta por mujeres (58 %) y por personas casadas (67 %). Fueron considerados como puntos de corte los 4, 7 y 10 años después de haber recibido el resultado de la PPS. Resultados: las mujeres y los viudos presentan las medias más altas. Los participantes con EMJ presentaron las medias más elevadas. No se encontraron diferencias significativas en lo concerniente a los resultados de PPS. La perturbación psicológica fue escasamente observada en los sujetos portadores que ya evidenciaban síntomas. Conclusiones: la aparición de los primeros síntomas parece constituir el detonante para la existencia de perturbaciones psicológicas, independientemente del intervalo de tiempo sucedido desde la comunicación de los resultados de la PPS o de la condición genética (portador/no portador).info:eu-repo/semantics/publishedVersio

Rare occurrence of severe blindness and deafness in Friedreich ataxia: a case report

Background: Friedreich ataxia is the most frequent hereditary ataxia worldwide. Subclinical visual and auditory involvement has been recognized in these patients, with co-occurrence of severe blindness and deafness being rare. Case report: We describe a patient, homozygous for a 873 GAA expansion in the FXN gene, whose first symptoms appeared by the age of 8. At 22 years-old he developed sensorineural deafness, and at 26 visual impairment. Deafness had a progressive course over 11 years, until a stage of extreme severity which hindered communication. Visual acuity had a catastrophic deterioration, with blindness 3 years after visual impairment was first noticed. Audiograms documented progressive sensorineural deafness, most striking for low frequencies. Visual evoked potentials disclosed bilaterally increased P100 latency. He passed away at the age of 41 years old, at a stage of extreme disability, blind and deaf, in addition to the complete phenotype of a patient with Friedreich ataxia of more than 30 years duration. Discussion: Severe vision loss and extreme deafness has been described in very few patients with Friedreich ataxia. Long duration, severe disease and large expanded alleles may account for such an extreme phenotype; nonetheless, the role of factors as modifying genes warrants further investigation in this subset of patients.info:eu-repo/semantics/publishedVersio

O bem-estar psicológico em indivíduos de risco para doenças neurológicas hereditárias de aparecimento tardio e controlos

No âmbito do protocolo do teste preditivo para doenças neurogenéticas de aparecimento tardio (Doença de Huntington, Doença de Machdo-Joseph e Polineuropatia Amiloidótica Familiar) aplicado a sujeitos em risco para estas doenças, investigamos o bem estar psicológico destes sujeitos. Averiguar se o bem estar psicológico dos sujeitos em risco, comparativamente com a população geral, é mais ou menos elevado. The Psychological General Well Being (PGWB) Index ( Escala de Bem Estar Psicológico Geral) foi desenvolvida com o objectivo de oferecer um índice que medisse as auto representações dos estados emocionais ou afectivos intrapessoais que reflectisse a noção subjectiva de bem estar ou distress. Comparamos os resultados do grupo de sujeitos em risco com o grupo de controlo: Existem diferenças significativas em relação aos factores ansiedade e bem estar positivo. O grupo em risco apresenta menos ansiedade e maior bem estar positivo. O grupo de risco tem indicadores de bem estar psicológico mais elevados do que o grupo de controlo. Seria de esperar que os sujeitos em risco de doença neurogenética de aparecimento tardio apresentassem valores mais baixos no que diz respeito ao bem estar psicológico geral, uma vez que estão relativamente conscientes do risco que correm de serem portadores duma doença desse tipo. Contudo, não é isso que verificamos, pelo contrário, o grupo de risco apresenta um maior bem estar psicológico em relação ao grupo de controlo. Concluímos que o grupo em risco de ser portador de gene de doença neurogenética de aparecimento tardio apresenta globalmente um maior bem estar psicológico do que o grupo de controlo. Os dados obtidos apontam para duas hipóteses: a) a de estarmos perante uma atitude defensiva e de negação por parte dos indivíduos de risco; b) a de estarmos perante indivíduos mais resistentes do ponto de vista psicológico, o que poderá ter motivado a auto-selecção para aderirem ao Teste Preditivo. ------ ABSTRACT ------- Psychological issues are important for counselling and intervention in late-onset diseases (Huntington Disease, Machado Joseph Disease and), namely in the process of adjustment to the results of genetic testing. Our aim was to evaluate psychological wellbeing in persons coming for presymptomatic testing comparing with normal population. The Psychological General Well Being (PGWB) Schedule was developed for the purpose of providing na index that could be used to measure self-representations of intrapersonal affective or emotional states reflecting a sense of subjective wellbeing or distress. We compared the results between the group of individuals at-risk and the control group: there are significative differences regarding the anxiety and positive wellbeing factors. The group at-risk presents less anxiety and more positive wellbeing. The group at-risk shows higher psychologycal wellbeing indicators than the control group. One may have expected that individuals at-risk who came for pre-symptomatic testing were more concerned about their health and showed more adverse indicators regarding their psychological wellbeing, since they are more aware of the risk of being or not a carrier of one of those diseases. Our results, however, proved to be different: the group at-risk presents less anxiety and more positive wellbeing and shows higher psychologycal wellbeing indicators than the control group. Facing those results we may suggest two possible explanations(a) a defensive and denial attitude from the group of individuals at-risk, and/or that (b) these are psychologically more resilient, what may have motivated adhesion to pre-symptomatic testing, through their own auto-selection

Between responsibility and desire: Accounts of reproductive decisions from those at risk for or affected by late-onset neurological diseases

This paper explores ways in which genetic risk foregrounds forms of responsibility while dealing with reproduction. We analyzed individual and family semi-structured interviews (n = 35) with people at-risk for or affected by transthyretin-related familial amyloid polyneuropathy (TTR-FAP) and Machado-Joseph disease (MJD), which are late-onset neurological diseases. Although generally considered as rare diseases, some areas in Portugal present the world's highest frequency for MJD and TTR-FAP. Thematic analysis of the data revealed that participants drew on various – sometimes ambivalent and competing – understandings of their genetic risk and their wish to have children. Some participants perceived the avoidance of genetic risk to be responsible behavior, while, for others, responsibility entailed accepting risks because they prioritized values such as parenthood, family relationships and the value of life, above any question of genetic disease. Some participants shared accounts that were fraught with ambivalence, repentance and guilt, especially when children were born before participants knew of their own or their partner's risk. Participants’ accounts also showed they make continued efforts to see themselves as responsible persons and to appear responsible in the eyes of others. We discuss findings in the context of participants’ negotiation between genetic risk and their sense of responsibility toward themselves and others; we conclude that “genetic responsibility” is present not only in accounts of those who chose not to have children but also in those who make an informed decision to have at-risk children

Motor and cognitive deficits in the heterozygous leaner mouse, a Cav2.1 voltage-gated Ca2+ channel mutant

Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.neurobiolaging.The leaner mutation in mice affects the Ca(v)2.1 voltage-gated calcium channel alpha(1A)-subunit gene (Cacna1a), causing a reduction in calcium currents predominantly in Purkinje cells. This reduction in calcium currents causes severe progressive cerebellar ataxia, beginning around postnatal day 10, in homozygous leaner mice (tg(la)/tg(la)), while their heterozygous littermates (tg(la)/+) present no obvious behavioral deficits. In humans, heterozygous mutations in the Cacna1a orthologous gene produce a broad range of neurological manifestations. To evaluate the phenotypic status of the tg(la)/+ animals, we assessed motor performance and cognition, at different ages, in these mutant mice. We were able to observe age-dependent impairment in motor and cognitive tasks; balance and motor learning deficits were found in demanding tasks on the rotarod and on the hanging wire test, while spatial learning and memory impairment was observed in the Morris water maze. Progressive dysfunction in escape reflexes, indicative of neurological impairment, was also present in tg(la)/+ animals. Although not presenting major motor alterations, tg(la)/+ mice show age-dependent motor and cognitive deficits.We would like to thank Carolina Lemos for her help with statistical analysis and Victor Mendes for image technical assistance. This work was supported by research grants POCTI/MGI/34517/00, POCTI/NSE/45352/2002 and POCI/SAU-MMO/56387/2004, FCT (Fundação para a Ciência e Tecnologia) and co-funded by FEDER. I.A. is recipient of a scholarship from FCT, Portugal