The Experts below are selected from a list of 1947 Experts worldwide ranked by ideXlab platform
Mariaceu Moreira - One of the best experts on this subject based on the ideXlab platform.
-
chapter 10 recessive ataxia plus oculomotor apraxia syndromes
Blue Books of Neurology, 2007Co-Authors: Michel Koenig, Mariaceu MoreiraAbstract:Publisher Summary Ataxia with oculomotor apraxia (AOA) is a newly recognized group of recessive ataxias that associate ataxia due to cerebellar atrophy with peripheral Sensorimotor Neuropathy. Unlike what the name suggests, oculomotor apraxia is not an absolute feature of AOA but is a useful diagnostic aid when present. This chapter discusses recessive ataxia plus oculomotor apraxia syndromes. Molecular genetic studies have delineated a novel group of recessive ataxias defined by the association of cerebellar atrophy and peripheral Sensorimotor Neuropathy. This group includes ataxia with oculomotor apraxia form 1, defined by late hypoalbuminemia and hypercholesterolemia; ataxia with oculomotor apraxia form 2, defined by moderately elevated serum α-fetoprotein (AFP); ataxia-telangiectasia-like disease without elevated serum AFP; and spinocerebellar ataxia with Neuropathy (SCAN1), also associated with late hypoalbuminemia. For all four inherited diseases, the gene encodes for a nuclear protein (aprataxin, senataxin, MRE11, and tyrosyl-DNA phosphodiesterase, respectively), which is or may be involved in DNA repair, although the disease causing mutations do not result in cancer predisposition.
-
Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2
Nature Genetics, 2004Co-Authors: Mariaceu Moreira, Sandra Klur, José-carlos Moniz, Andrea H. Németh, Christine Tranchant, Patrick Aubourg, Mitsunori Watanabe, Meriem Tazir, Ludger Schols, Massimo PandolfoAbstract:Ataxia-ocular apraxia 2 (AOA2) was recently identified as a new autosomal recessive ataxia. We have now identified causative mutations in 15 families, which allows us to clinically define this entity by onset between 10 and 22 years, cerebellar atrophy, axonal Sensorimotor Neuropathy, oculomotor apraxia and elevated alpha-fetoprotein (AFP). Ten of the fifteen mutations cause premature termination of a large DEAxQ-box helicase, the human ortholog of yeast Sen1p, involved in RNA maturation and termination.
-
cerebellar ataxia with oculomotor apraxia type 1 clinical and genetic studies
Brain, 2003Co-Authors: Mariaceu Moreira, Celine Chamayou, Marie-odile Habert, F. Ochsner, Thierry Kuntzer, Geneviève Demarquay, Gérard Said, Sophie Rivaudpechoux, Marc Tardieu, Christian TannierAbstract:Summary Ataxia with ocular motor apraxia type 1 (AOA1) is an autosomal recessive cerebellar ataxia (ARCA) associated with oculomotor apraxia, hypoalbuminaemia and hypercholesterolaemia. The gene APTX, which encodes aprataxin, has been identified recently. We studied a large series of 158 families with non-Friedreich progressive ARCA. We identified 14 patients (nine families) with five different missense or truncating mutations in the aprataxin gene (W279X, A198V, D267G, W279R, IVS5+1), four of which were new. We determined the relative frequency of AOA1 which is 5%. Mutation carriers underwent detailed neurological, neuropsychological, electrophysiological, oculographic and biological examinations, as well as brain imaging. The mean age at onset was 6.8 6 4.8 years (range 2‐18 years). Cerebellar ataxia with cerebellar atrophy on MRI and severe axonal Sensorimotor Neuropathy were present in all patients. In contrast, oculomotor apraxia (86%), hypoalbuminaemia (83%) and hypercholesterolaemia (75%) were variable. Choreic movements were frequent at onset (79%), but disappeared in the course of the disease in most cases. However, a remarkably severe and persistent choreic phenotype was associated with one of the mutations (A198V). Cognitive impairment was always present. Ocular saccade initiation was normal, but their duration was increased by the succession of multiple hypometric saccades that could clinically be confused with ‘slow saccades’. We emphasize the phenotypic variability over the course of the disease. Cerebellar ataxia and/or chorea predominate at onset, but later on they are often partially masked by severe Neuropathy, which is the most typical symptom in young adults. The presence of chorea, Sensorimotor Neuropathy, oculomotor anomalies, biological abnormalities, cerebellar atrophy on MRI and absence of the Babinski sign can help to distinguish AOA1 from Friedreich’s ataxia on a clinical basis. The frequency of chorea at onset suggests that this diagnosis should also be considered in children with chorea who do not carry the IT15 mutation responsible for Huntington’s disease.
Sinead M Murphy - One of the best experts on this subject based on the ideXlab platform.
-
expanding the phenotype of slc12a6 associated Sensorimotor Neuropathy
Case Reports, 2021Co-Authors: Petya Bogdanovamihaylova, Patricia Mcnamara, Sarah Burtonjones, Sinead M MurphyAbstract:Hereditary motor and sensory Neuropathy with agenesis of the corpus callosum (HMSN/ACC) is a rare autosomal recessive condition characterised by early-onset severe progressive Neuropathy, variable degrees of ACC and cognitive impairment. Mutations in SLC12A6 (solute carrier family 12, member 6) encoding the K+-Cl- transporter KCC3 have been identified as the genetic cause of HMSN/ACC. We describe fraternal twins with compound heterozygous mutations in SLC12A6 and much milder phenotype than usually described. Neither of our patients requires assistance to walk. The female twin is still running and has a normal intellect. Charcot-Marie-Tooth Examination Score 2 was 8/28 in the brother and 5/28 in the sister. Neurophysiology demonstrated a length-dependent Sensorimotor Neuropathy. MRI brain showed normal corpus callosum. Genetic analysis revealed compound heterozygous mutations in SLC12A6, including a whole gene deletion. These cases expand the clinical and genetic phenotype of this rare condition and highlight the importance of careful clinical phenotyping.
-
waardenburg syndrome a rare cause of inherited Neuropathy due to sox10 mutation
Journal of The Peripheral Nervous System, 2017Co-Authors: Petya Bogdanovamihaylova, Sinead M Murphy, Michael D Alexander, Raymond P MurphyAbstract:Waardenburg syndrome (WS) is a rare disorder comprising sensorineural deafness and pigmentation abnormalities. Four distinct subtypes are defined based on the presence or absence of additional symptoms. Mutations in six genes have been described in WS. SOX10 mutations are usually associated with a more severe phenotype of WS with peripheral demyelinating Neuropathy, central dysmyelinating leukodystrophy, and Hirschsprung disease. Here we report a 32-year-old man with a novel heterozygous missense variant in SOX10 gene, who presented with congenital deafness, Hirschsprung disease, iris heterochromia, foot deformity, and intermediate conduction velocity length-dependent Sensorimotor Neuropathy. This case highlights that the presence of other non-neuropathic features in a patient with presumed hereditary Neuropathy should alert the clinician to possible atypical rare causes.
-
bag3 mutations another cause of giant axonal Neuropathy
Journal of The Peripheral Nervous System, 2012Co-Authors: Fatima Jaffer, Alexander M. Rossor, Sinead M Murphy, Mariacristina Scoto, Estelle Healy, Sebastian Brandner, R Phadke, Duygu Selcen, Heinz JungbluthAbstract:: Mutations in Bcl-2 associated athanogene-3 (BAG3) are a rare cause of myofibrillar myopathy, characterised by rapidly progressive proximal and axial myopathy, cardiomyopathy and respiratory compromise. Neuropathy has been documented neurophysiologically in previously reported cases of BAG3-associated myofibrillar myopathy and in some cases giant axons were observed on nerve biopsies; however, Neuropathy was not thought to be a dominant feature of the disease. In the context of inherited Neuropathy, giant axons are typically associated with autosomal recessive giant axonal Neuropathy caused by gigaxonin mutations but have also been reported in association with NEFL- and SH3TC2-associated Charcot-Marie-Tooth disease. Here, we describe four patients with heterozygous BAG3 mutations with clinical evidence of a Sensorimotor Neuropathy, with predominantly axonal features on neurophysiology. Three patients presented with a significant Neuropathy. Muscle magnetic resonance imaging (MRI) in one patient revealed mild to moderate atrophy without prominent selectivity. Examination of sural nerve biopsies in two patients demonstrated giant axons. This report confirms the association of giant axonal Neuropathy with BAG3-associated myofibrillar myopathy, and highlights that Neuropathy may be a significant feature.
D. Michel - One of the best experts on this subject based on the ideXlab platform.
-
paraneoplastic peripheral Neuropathy associated with anti hu antibodies a clinical and electrophysiological study of 20 patients
Journal of The Peripheral Nervous System, 2002Co-Authors: Jeanphilippe Camdessanche, Jérome Honnorat, Philippe Petiot, P Convers, Christophe Vial, Jean-christophe Antoine, D. MichelAbstract:Summary Although paraneoplastic subacute sensory neuronopathy is the most frequent presentation of peripheral neuropa- thy in patients with anti-Hu antibodies, other neuropa- thies have been reported. In order to investigate the clinical and electrophysiological manifestations of neu- ropathies associated with anti-Hu antibodies, we con- ducted a retrospective study of 20 patients. For the electrophysiological study, each nerve was classified as normal, demyelinating, axonal/neuronal or axonal/ demyelinating. Peripheral Neuropathy was the present- ing symptom in 95% of patients. CNS and autonomic Neuropathy were present in 40% and 30% of patients, respectively. The course of the Neuropathy was acute, mimicking Guillain-Barresyndrome in one patient (5%), and subacute (55%) or progressive (40%) in the others. Clinically, the Neuropathy was sensory (70%), Sensorimotor (25%) or motor (5%). At onset, symptoms were symmetrical (65%), asymmetrical (25%) or multi- focal (10%). Pain was a predominant manifestation (80%). Amyotrophia and fasciculations were rare. The median Rankin's score was 2, three patients having an indolent form. Electrophysiology showed the axonal/ neuronal pattern to be the most frequent (46.9% of studied nerves); an axonal/demyelinating or demyelinat- ing pattern being seen in 18.3% and 4.9% of nerves, respectively. The axonal/neuronal pattern was more fre- quent in sensory nerves and the mixed axonal/demyeli- nating pattern more frequent in motor nerves (P < 0.01). A higher proportion of abnormal nerves correlated with a progressive course (P < 0.05) or a Rankin's score between 3 and 5 (P < 0.01). In patients with sensory Neuropathy, 88.5% of sensory nerves were abnormal, mostly with an axonal/neuronal pattern. In addition, 47% of motor nerves were abnormal so that only four out of 14 patients with a clinically pure sensory neuro- pathy (28.6%) had an electrophysiological pattern typ- ical of sensory neuronopathy. In patients with a Sensorimotor Neuropathy, 96.6% of sensory and 71% of motor nerves were abnormal. The only statistical differ- ence between sensory and Sensorimotor neuropathies was that patients with Sensorimotor Neuropathy had more frequent motor nerve involvement (P < 0.05) with- out differences concerning the distribution of the abnor- mal patterns. Needle neuromyography showed only limited evidence of motor neurone degeneration in both sensory and Sensorimotor Neuropathy. The present work shows that the typical clinical and electrophysiolo- gical pattern of subacute sensory neuronopathy is rarely encountered in patients with anti-Hu antibody and that motor nerve involvement is frequently seen, even in the absence of a motor deficit. In addition to their potential pathophysiological involvement in the mechanism of the paraneoplastic Neuropathy, these findings have practical consequences for the diagnosis of the disorder.
-
paraneoplastic peripheral Neuropathy associated with anti hu antibodies a clinical and electrophysiological study of 20 patients
Brain, 2002Co-Authors: Jeanphilippe Camdessanche, Jérome Honnorat, Philippe Petiot, P Convers, Christophe Vial, Jean-christophe Antoine, D. MichelAbstract:Although paraneoplastic subacute sensory neuronopathy is the most frequent presentation of peripheral Neuropathy in patients with anti‐Hu antibodies, other neuropathies have been reported. In order to investigate the clinical and electrophysiological manifestations of neuropathies associated with anti‐Hu antibodies, we conducted a retrospective study of 20 patients. For the electrophysiological study, each nerve was classified as normal, demyelinating, axonal/neuronal or axonal/demyelinating. Peripheral Neuropathy was the presenting symptom in 95% of patients. CNS and autonomic Neuropathy were present in 40% and 30% of patients, respectively. The course of the Neuropathy was acute, mimicking Guillain–Barre syndrome in one patient (5%), and subacute (55%) or progressive (40%) in the others. Clinically, the Neuropathy was sensory (70%), Sensorimotor (25%) or motor (5%). At onset, symptoms were symmetrical (65%), asymmetrical (25%) or multifocal (10%). Pain was a predominant manifestation (80%). Amyotrophia and fasciculations were rare. The median Rankin’s score was 2, three patients having an indolent form. Electrophysiology showed the axonal/neuronal pattern to be the most frequent (46.9% of studied nerves); an axonal/demyelinating or demyelinating pattern being seen in 18.3% and 4.9% of nerves, respectively. The axonal/neuronal pattern was more frequent in sensory nerves and the mixed axonal/demyelinating pattern more frequent in motor nerves ( P < 0.01). A higher proportion of abnormal nerves correlated with a progressive course ( P < 0.05) or a Rankin’s score between 3 and 5 ( P < 0.01). In patients with sensory Neuropathy, 88.5% of sensory nerves were abnormal, mostly with an axonal/neuronal pattern. In addition, 47% of motor nerves were abnormal so that only four out of 14 patients with a clinically pure sensory Neuropathy (28.6%) had an electrophysiological pattern typical of sensory neuronopathy. In patients with a Sensorimotor Neuropathy, 96.6% of sensory and 71% of motor nerves were abnormal. The only statistical difference between sensory and Sensorimotor neuropathies was that patients with Sensorimotor Neuropathy had more frequent motor nerve involvement ( P < 0.05) without differences concerning the distribution of the abnormal patterns. Needle neuromyography showed only limited evidence of motor neurone degeneration in both sensory and Sensorimotor Neuropathy. The present work shows that the typical clinical and electrophysiological pattern of subacute sensory neuronopathy is rarely encountered in patients with anti‐Hu antibody and that motor nerve involvement is frequently seen, even in the absence of a motor deficit. In addition to their potential pathophysiological involvement in the mechanism of the paraneoplastic Neuropathy, these findings have practical consequences for the diagnosis of the disorder. Received May 21, 2001. Revised July 31, 2001. Accepted August 13, 2001.
Mary D. King - One of the best experts on this subject based on the ideXlab platform.
-
atypical presentation of ataxia oculomotor apraxia type 1
Developmental Medicine & Child Neurology, 2006Co-Authors: Amre Shahwan, Malcolm A R Taylor, Therese Nestor, Stephanie Ryan, Philip J Byrd, Mary D. KingAbstract:A subgroup of autosomal recessive cerebellar ataxias (ARCAs) associated with oculomotor apraxia (OMA) and other variable features has been reported. Ataxia-oculomotor apraxia types 1 and 2 (AOA1 and AOA2) belong to this subgroup and have been described in adults with early onset cerebellar ataxia. AOA1 is associated with oculomotor apraxia, severe Sensorimotor Neuropathy, choreiform movements, cognitive impairment, and cerebellar atrophy at an early age. We describe a male child with AOA1 who is homozygous for the G837A (W279X) mutation in the APTX gene. He presented at the age of 3 years 6 months with some atypical features including absence of OMA, chorea, and cerebellar atrophy. These manifestations, in addition to peripheral Neuropathy, appeared at 8 years of age. We highlight the importance of considering the diagnosis of AOA1 in children with early-onset cerebellar ataxia, once other well-known disorders such as Friedreich's ataxia and ataxia-telangiectasia have been excluded.
Tulio E Bertorini - One of the best experts on this subject based on the ideXlab platform.
-
mitochondrial neurogastrointestinal encephalomyopathy mngie clinical biochemical and genetic features of an autosomal recessive mitochondrial disorder
Neurology, 1994Co-Authors: Michio Hirano, Anne Lombès, Eduardo Bonilla, G Silvestri, D M Blake, Carlo Minetti, Arthur P Hays, Robert E Lovelace, Ian J Butler, Tulio E BertoriniAbstract:We studied the clinical, biochemical, and genetic features of eight patients with the autosomal recessive mitochondrial syndrome mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). MNGIE is clinically characterized by ophthalmoparesis, peripheral Neuropathy, leukoencephalopathy, gastrointestinal symptoms (recurrent nausea, vomiting, or diarrhea) with intestinal dysmotility, and histologically abnormal mitochondria in muscle. Brain MRI scans were consistent with leukodystrophy in seven patients examined. Nerve conduction and EMG studies were compatible with a Sensorimotor Neuropathy; quantitative EMG of two patients suggested a myogenic process. Muscle mitochondrial enzyme analysis revealed a partial defect of cytochrome c oxidase activity in five patients; three had additional respiratory chain enzyme defects. Two patients had isolated complex I defects, and one had normal respiratory chain function. Southern blot analysis revealed multiple deletions of mitochondrial DNA in four of eight patients.
