RESUMO
BACKGROUND: The diagnostic workup for choreiform movement disorders including Huntington's disease (HD) and those mimicking HD like phenotype is complex. OBJECTIVE: The aim of the present study was to genetically define HD and HD-like presentations in an Indian cohort. We also describe HTT-CAG expansion manifesting as neuroferritinopathy-like disorder in four families from Punjab in India. MATERIALS AND METHODS: 159 patients clinically diagnosed as HD and HD-like presentations from various tertiary neurology clinics were referred to our centre (CSIR-IGIB) for genetic investigations. As a first tier test, CAG-TNR for HTT was performed and subsequently HD-negative samples were screened for JPH3 (HDL2), TBP (SCA17), ATN1 (DRPLA), PPP2R2B (SCA12) and GGGGCC expansion in C9orf72 gene. Four families presenting as neuroferritinopathy-like disorder were also investigated for HTT-CAG expansion. RESULTS: 94 of 159 (59%) patients were found to have expanded HTT-CAG repeats. Pathogenic repeat expansion in JPH3, TBP, ATN1 and C9orf72 were not found in HD negative cases. Two patients were positive for SCA12-CAG expansion in pathogenic length, whereas 5 cases harboured TBP-CAG repeats falling in reduced penetrance range of 41- 48 repeats for SCA17. Four unrelated families, presented with atypical chorea and brain MRI findings suggestive of basal ganglia abnormalities mimicking neuroferritinopathy were found to harbour HTT-CAG expansion. CONCLUSION: We present SCA12 as a new reported phenocopy of HD which should be considered for diagnostic workout along with SCA17 for HD-like syndromes. This study also illustrates the necessity, to consider evolving HD like phenotype, as a clinical diagnosis for cases with initial manifestations depicting neuroferritinopathy.
Assuntos
Transtornos Heredodegenerativos do Sistema Nervoso/diagnóstico , Doença de Huntington/diagnóstico , Distúrbios do Metabolismo do Ferro/diagnóstico , Distrofias Neuroaxonais/diagnóstico , Expansão das Repetições de Trinucleotídeos/genética , Adulto , Feminino , Testes Genéticos , Transtornos Heredodegenerativos do Sistema Nervoso/genética , Humanos , Proteína Huntingtina , Doença de Huntington/genética , Índia , Distúrbios do Metabolismo do Ferro/genética , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso , Distrofias Neuroaxonais/genética , Proteína Fosfatase 2 , Proteína de Ligação a TATA-BoxRESUMO
BACKGROUND: People with epilepsy (PWE) beginning in childhood often experience psychological and social hold-ups in addition to seizures. The hold-ups relate to education, employment, driving, and marriage. OBJECTIVE: The objective of this study was to document the impact of long-standing, childhood-onset epilepsy on sociopersonal accomplishments of adults pertaining to education, employment, marriage, and driving. METHODS: A prospective, questionnaire-based survey was undertaken in a hospital-based sample of PWE and their unaffected (by epilepsy) older siblings within the immediate/extended family unit. RESULTS: People with epilepsy were significantly more likely to abandon formal education after primary (6; 2.4% compared to none in controls) or secondary (69; 31.1% compared with controls 58; 26.1%) school, less likely to be currently married (97; 43.7%) when compared with their elder siblings (158; 71.2%) (Pâ¯=â¯0.0001), and less likely to be currently employed (103; 46.4%) (Pâ¯=â¯0.0001) or driving (111; 50%) (Pâ¯=â¯0.0001) compared with the older same-gender siblings (employed: 148; 66.7%; driving: 165; 74.3%). In multivariate models, having epilepsy and age were associated with employment status, whereas age and education and employment status were associated with both marriage and driving. CONCLUSION: Notwithstanding the influence of a number of socioeconomic and epilepsy-related variables, childhood-onset epilepsy stands apart in exerting a huge negative impact on educational achievement, employability, marital status, and driving in adulthood.