1/36. A new case of frontotemporal dementia and parkinsonism resulting from an intron 10 3-splice site mutation in the tau gene: clinical and pathological features.Hereditary frontotemporal dementia and parkinsonism (FTDP) linked to chromosome 17 (FTDP-17) constitutes a new form of tauopathy, and mutations in the tau gene have recently been reported in some affected families. This report presents clinical and neuropathological data from a member of a British family (SOT 254) with a history of dementia and movement disorder. The medical history of the affected patient, a woman aged 44 years, was reviewed, and a detailed post-mortem examination of the brain was undertaken. A panel of well characterized phosphorylation-dependent and independent anti-tau antibodies was used to assess tau pathology, and inclusions were examined by electron microscopy. Neuronal loss and gliosis were widely distributed, but most severe in neocortical regions, and were associated with abundant neuronal and glial tau inclusions which consisted of a mixture of paired helical filaments (PHFs), similar to those in Alzheimer's disease, and distinct twisted ribbon-like filaments. Genomic dna was obtained from post-mortem tissue from the index patient, and blood from two unaffected members of the same family. For the index case only, sequencing of intronic sequences flanking exon 10 of the tau gene identified a G to A transition at position 3 of the splice-donor site downstream of exon 10, identical to that reported in multiple system tauopathy with presenile dementia (MSTD). The clinical, neuropathological and genetic findings strongly suggest that SOT 254 represents a new example of FTDP-17 resulting from a mutation in the tau gene. These results are compared with those reported for other FTDP-17 families, i.e. for MSTD.- - - - - - - - - - ranking = 1keywords = family, member (Clic here for more details about this article) |
2/36. Neuronal intranuclear inclusion disease and juvenile parkinsonism.Juvenile parkinsonism (onset age <20 yrs) is uncommon and few cases with neuropathologic confirmation have been reported. We present the case of a 17-year-old boy who presented with asymmetric arm tremor and bulbar symptoms. His paternal great aunt had parkinsonism with onset at age 22 years. Examination revealed parkinsonism in the absence of additional neurologic signs except for delayed pupillary responses to light. He responded well to levodopa but developed motor fluctuations and disabling dyskinesias after 3 years of treatment. Following attempted withdrawal of levodopa at age 24 years, he developed severe aspiration pneumonia complicated by cardiorepiratory arrests and he died 6 months later. At autopsy, the dominant histologic feature was wide-spread neuronal hyaline intranuclear inclusions. Neuronal depletion was observed in the substantia nigra, locus ceruleus, and, to a lesser extent, in the frontal cortex, and inclusions were particularly prominent in these areas. Inclusions were immunoreactive for ubiquitin and were typical of those seen in neuronal intranuclear inclusion disease (NIID), a rare, multisytem neurodegenerative disease. NIID should be considered in the differential diagnosis of juvenile parkinsonism. A link between NIID and hereditary neurodegenerative disorders characterized by expanded polyglutamine tracts is supported by the similar appearance of intranuclear inclusions in both conditions and by a family history in some cases of NIID.- - - - - - - - - - ranking = 0.49317279310443keywords = family (Clic here for more details about this article) |
3/36. Clinical and pathologic abnormalities in a family with parkinsonism and parkin gene mutations.A Dutch family with autosomal recessive early-onset parkinsonism showed a heterozygous missense mutation in combination with a heterozygous exon deletion in the parkin gene. Although the main clinical syndrome consisted of parkinsonism, the proband clinically had additional mild gait ataxia and pathologically showed neuronal loss in parts of the spinocerebellar system, in addition to selective loss of dopaminergic neurons in the substantia nigra pars compacta. lewy bodies and neurofibrillary tangles were absent, but tau pathology was found.- - - - - - - - - - ranking = 2.4658639655221keywords = family (Clic here for more details about this article) |
4/36. Familial parkinsonism with synuclein pathology: clinical and PET studies of A30P mutation carriers.BACKGROUND: The authors identified the second known mutation in the alpha-synuclein(SNCA) gene, an alanine-to-proline exchange in amino acid position 30 (A30P), that cosegregates with the disease in one German family with autosomal dominantly inherited parkinsonism (ADP). The authors studied carriers of the A30P mutation to compare the phenotype of this mutation with idiopathic PD (IPD) and to assess nigrostriatal dopaminergic function in symptomatic and preclinical mutation carriers. methods: The pedigree of the A30P family spans five generations with five affected individuals. The authors performed detailed neurologic examinations followed by mutation analysis in 11 living individuals. In three mutation carriers, two individuals with definite PD and one person at risk for PD, they used L-[18]F-fluoro-3,4-dihydroxyphenylalanine (F-DOPA), [11]C-raclopride (RAC), and [18]F-fluorodeoxyglucose (FDG) PET to investigate presynaptic dopaminergic function, dopamine D2 receptors, and cerebral energy metabolism. The authors studied the cognitive functions of carriers of the A30P mutation using neuropsychological screening. RESULTS: PET studies revealed striatal presynaptic dopaminergic alterations consistent with sporadic IPD in two affected family members and no evidence for nigrostriatal dopaminergic dysfunction in one presymptomatic mutation carrier. Neuropsychological testing in four mutation carriers provided evidence for cognitive impairment as a frequent and early symptom of the A30P mutation; this is also supported by regional cerebral energy metabolism alterations in the clinically presymptomatic subject. CONCLUSIONS: The phenotype of the A30P mutation in the SNCA gene is similar to that of sporadic IPD, including a high variability of the age at disease onset, ranging from 54 to 76 years. The follow-up of presymptomatic carriers of the A30P mutation may give insight into preclinical disease stages and early manifestations of PD.- - - - - - - - - - ranking = 1.5496404967661keywords = family, family member, member (Clic here for more details about this article) |
5/36. frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17): PPND family. A longitudinal videotape demonstration.frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), characterized by an autosomal dominant inheritance pattern, has recently been recognized as a distinct entity that can display a confusingly broad clinical phenotype. The pallido-ponto-nigral degeneration (PPND) variant is the prototypical example of the parkinsonism-predominant pattern of FTDP-17. A longitudinal videotape demonstration of the clinical progression of this entity in a single individual, along with brief videotape segments from three additional affected individuals, is presented in order to facilitate recognition of this disorder.- - - - - - - - - - ranking = 1.9726911724177keywords = family (Clic here for more details about this article) |
6/36. Three parkin gene mutations in a sibship with autosomal recessive early onset parkinsonism.The objective was to describe a family with autosomal recessive, early onset parkinsonism, with affected siblings carrying three different exon rearrangements in the parkin gene.The living affected siblings were personally examined. Molecular genetic analyses included exon dosage of the parkin gene using a semiquantitative multiplex polymerase chain reaction (PCR) protocol and haplotype analysis.The index case was a compound heterozygote with a deletion of exon 5 and a duplication of exon 3. His affected sister was a compound heterozygote for a deletion of exon 5 and a deletion of exons 3-9. Haplotype analysis confirmed the presence of three mutant alleles at the parkin locus. The phenotype was early onset parkinsonism with marked response to levodopa, and a very slow, prolonged course.In conclusion, the frequency of mutations in the parkin gene in certain populations might be high enough to cause allelic heterogeneity in the same sibship.- - - - - - - - - - ranking = 0.49317279310443keywords = family (Clic here for more details about this article) |
7/36. Phenotypic characterisation of autosomal recessive PARK6-linked parkinsonism in three unrelated Italian families.The clinical features of nine patients (three women and six men) affected by PARK6-linked parkinsonism, belonging to three unrelated Italian families, are reported. The occurrence of affected men and women within one generation suggested an autosomal recessive mode of inheritance in all three families. Mean age at disease onset was 36 /- 4.6 years; all cases except one presented with asymmetrical signs, consisting of tremor and akinesia of one upper limb or unilateral short step gait. Affected individuals had a mean age of 57 /- 8.5 years, and average disease duration was 21 /- 7.8 years. Parkinsonian features included benign course, early onset of drug-induced dyskinesias, and a good and persistent response to levodopa. There were no other associated features (i.e., pyramidal or cerebellar signs, dysautonomia, or diurnal fluctuations unrelated to drug treatment). cognition was unaffected. The clinical picture was remarkably similar in all patients; no relevant family-related differences were found. PARK6 disease is a new form of early-onset parkinsonism without other atypical clinical features.- - - - - - - - - - ranking = 0.49317279310443keywords = family (Clic here for more details about this article) |
8/36. life-threatening parkinsonism induced by kava-kava.We present a 45-year-old female with severe parkinsonism induced by kava-kava. The patient, who had a family history of essential tremor, developed severe and persistent parkinsonism after days of treatment with kava extract for anxiety. The symptoms improved with anticholinergics. kava derivatives could produce severe parkinsonism in individuals with genetic susceptibility.- - - - - - - - - - ranking = 0.49317279310443keywords = family (Clic here for more details about this article) |
9/36. Familial diffuse lewy body disease, eye movement abnormalities, and distribution of pathology.BACKGROUND: Familial diffuse lewy body disease (DLBD) is rare and not yet associated with a defect in the synuclein gene. In the differential diagnosis of the parkinsonian syndromes, defects in vertical gaze tend to be identified with progressive supranuclear palsy. False-positive diagnosis of progressive supranuclear palsy can occur, and defects in vertical gaze have been reported in DLBD, although so far a pure vertical gaze palsy associated with pathological abnormalities in the substrate for vertical gaze has not been described. OBJECTIVES: To report the clinical and pathological findings in 2 siblings with DLBD, and to relate the distribution of the pathological abnormalities in the brainstem to centers for vertical gaze. MATERIALS: For several years, 2 Irish siblings experienced a progressive parkinsonism-dementia complex associated in one with a defect in vertical gaze and in both with visual hallucinations. RESULTS: In both patients, results of pathological examination revealed (1) Lewy bodies positive for ubiquitin and alpha-synuclein together with cell loss and gliosis in the substantia nigra, locus ceruleus, and neocortex; and (2) similar findings in the rostral interstitial nucleus of the medial longitudinal fasciculus, the posterior commissure, and the interstitial nucleus of Cajal (substrates for vertical gaze). CONCLUSIONS: Familial DLBD (not shown to be genetically as distinct from environmentally transmitted) has been shown to exist in an Irish family. Caution should be enjoined in the interpretation of defects in vertical gaze in the differential diagnosis of the parkinsonian syndromes.- - - - - - - - - - ranking = 0.49317279310443keywords = family (Clic here for more details about this article) |
10/36. Neuropathology of two members of a German-American kindred (family C) with late onset parkinsonism.We present genealogical and longitudinal clinical observations and autopsy findings of a previously reported kindred, family C (German-American), with late-onset autosomal dominant parkinsonism with evidence for linkage on chromosome 2p13. The clinical phenotype includes the cardinal features of idiopathic Parkinson's disease. In addition, postural tremor and dementia are detected in some individuals. Two members of the kindred, one affected and one unaffected have recently come to autopsy. The unaffected family member was an 82-year-old woman whose brain showed only mild age-related pathology and no evidence of subclinical lewy body disease. In contrast, the affected family member was an 83-year-old man whose brain had neuronal loss, gliosis and lewy bodies in the substantia nigra and other monoaminergic brain stem nuclei, as well as the basal forebrain and amygdala. lewy bodies and Lewy neurites had a distribution typical of cases of idiopathic Parkinson's disease. Thus, the clinical and pathological findings in this family with autosomal dominant parkinsonism are similar to those of sporadic Parkinson's disease.- - - - - - - - - - ranking = 1.6538986486968keywords = family, family member, member (Clic here for more details about this article) |
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