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Nancy B Spinner - One of the best experts on this subject based on the ideXlab platform.
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ring Chromosome 20
European Journal of Medical Genetics, 2012Co-Authors: Robert Daber, Laura K Conlin, Laura D Leonard, Maria Paola Canevini, Aglaia Vignoli, Syed A Hosain, Lawrence W Brown, Nancy B SpinnerAbstract:Ring Chromosome 20 syndrome is a rare chromosomal disorder characterized by refractory epilepsy, with seizures in wakefulness and sleep, behavioral problems and mild to severe cognitive impairment. Facial dysmorphism or other congenital malformations are rarely reported making it difficult to diagnose the syndrome based on clinical findings alone. Therefore, diagnosis requires cytogenetic testing. More than 100 cases have been published since the initial report in 1972. In some patients, the ring (20) is found in all cells analyzed and in these cases, the ring is almost always accompanied by deletions of 20pter and/or 20qter. However, in the majority of cases the ring is present in only a proportion of cells, with two normal 20's in the remaining cells (mosaicism), and in these cases, no deletions of Chromosome 20 have been observed. Patients with supernumerary r(20) Chromosomes have also been identified, but these individuals do not generally have seizures and are not discussed in this review. Characterization by fluorescence in situ hybridization and array-based analysis has shed insight into the molecular composition and possible mechanisms of ring formation, in both the mosaic and non-mosaic patients. The age of onset of seizures correlates with the percentage of cells with the ring in mosaic patients. While the underlying etiology of the phenotype is still not understood, evidence is accumulating which suggests the deletion of candidate genes on Chromosome 20 is not responsible. Cytogenetic analysis, rather than chromosomal microarray analysis is recommended for diagnosis of this syndrome, as the mosaic cases do not have copy number alterations and are therefore not identified by array-based analysis.
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ring Chromosome 20 epilepsy syndrome an overview
Journal of Pediatric Epilepsy, 2012Co-Authors: Syed A Hosain, Laura K Conlin, Nancy B SpinnerAbstract:The ring Chromosome 20 [r(20)], epilepsy syndrome is a relatively under-diagnosed epilepsy syndrome that has a striking association with seizures, which is not seen with other morphological aberrations of Chromosome 20. This syndrome is characterized by medically intractable complex partial epilepsy, subtle nocturnal frontal seizures, behavioral problems and mild mental impairment. In contrast to other epilepsy syndromes with chromosomal aberrations, dysmorphism (major or minor congenital malformations) and developmental delays are rarely reported. This lack of dysmorhism and relatively normal development in early life leads to delay in diagnosis. Additionally chromosomal testing is rarely considered in a patient with severe early onset epilepsy who does not have dysmorphic features, but this is the usual phenotype of r(20) epilepsy syndrome. More than 60 cases of r(20) have been reported in the literature. To date there is still no published data on the incidence and prevalence of this syndrome. This disorder appears to be pan-ethnic and non-gender specific. Cases of this syndrome have been identified in different parts of the world involving different ethnicities. Epilepsy in r(20) is often intractable with frontal lobe features. Non-convulsive status epilepticus and nocturnal seizures are frequently noted as are frontal lobe epileptiform electroencephalography abnormalities. Structural brain imaging is normal in most cases and is non-contributory. Definitive diagnosis can only be made by chromosomal analysis with mosaic screening. With more widespread cytogenetic chromosomal karyotyping in non-etiological cases of epilepsy, more cases of r(20) will undoubtedly be recognized.
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molecular analysis of ring Chromosome 20 syndrome reveals two distinct groups of patients
Journal of Medical Genetics, 2011Co-Authors: Laura K Conlin, Syed A Hosain, Samuel F Berkovic, Whitney Kramer, Anne L Hutchinson, Harold Riethman, Hakon Hakonarson, John C Mulley, Ingrid E Scheffer, Nancy B SpinnerAbstract:Background The ring Chromosome 20 syndrome (R20) is a rare genetic disorder associated with a refractory electroclinical epilepsy syndrome and variably expressed comorbidities of intellectual disability and dysmorphism. Methods To understand the structure and composition of the ring Chromosome 20 (r(20)) in this patient cohort, blood specimens from 28 affected individuals were analysed by cytogenetic, fluorescence in situ hybridisation, and/or high resolution whole genome single nucleotide polymorphism array analysis. Results These studies revealed two distinct groups of patients. Group 1 (N=21) was mosaic for the r(20) and a normal cell line with no detectable deletions or duplications of Chromosome 20 in either cell line. The mosaic nature of these rings suggests a postzygotic origin with formation of the ring by fusion of the telomeric regions with no apparent loss of subtelomeric or telomeric DNA. Group 2 (N=7) had non-mosaic ring Chromosomes with a deletion at one or both ends of the Chromosome, near the ring fusion point. The non-mosaic nature of these rings is consistent with a meiotic origin. The age of onset of seizures was significantly lower in the non-mosaic patients (group 2, median age of onset 2.1 years) than in the mosaic patients (group 1, median age of onset 6.0 years). Patients from group 2 had more extensive comorbidities. Conclusions These studies demonstrate that r(20) is molecularly heterogeneous and formed by two distinct mechanisms, which, in turn, produce different phenotypic spectrums.
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two siblings with alternate unbalanced recombinants derived from a large cryptic maternal pericentric inversion of Chromosome 20
American Journal of Medical Genetics Part A, 2010Co-Authors: Cheryl Descipio, Laura K Conlin, Nancy B Spinner, Harold Riethman, Jennifer J D Morrissette, Dinah Clark, Maninder Kaur, James Coplan, Ian D KrantzAbstract:: Two brothers, with dissimilar clinical features, were each found to have different abnormalities of Chromosome 20 by subtelomere fluorescence in situ hybridization (FISH). The proband had deletion of 20p subtelomere and duplication of 20q subtelomere, while his brother was found to have a duplication of 20p subtelomere and deletion of 20q subtelomere. Parental cytogenetic studies were initially thought to be normal, both by G-banding and by subtelomere FISH analysis. Since Chromosome 20 is a metacentric Chromosome and an inversion was suspected, we used anchored FISH to assist in identifying a possible inversion. This approach employed concomitant hybridization of a FISH probe to the short (p) arm of Chromosome 20 with the 20q subtelomere probe. We identified a cytogenetically non-visible, mosaic pericentric inversion of one of the maternal Chromosome 20 homologs, providing a mechanistic explanation for the chromosomal abnormalities present in these brothers. Array comparative genomic hybridization (CGH) with both a custom-made BAC and cosmid-based subtelomere specific array (TEL array) and a commercially available SNP-based array confirmed and further characterized these rearrangements, identifying this as the largest pericentric inversion of Chromosome 20 described to date. TEL array data indicate that the 20p breakpoint is defined by BAC RP11-978M13, approximately 900 kb from the pter; SNP array data reveal this breakpoint to occur within BAC RP11-978M13. The 20q breakpoint is defined by BAC RP11-93B14, approximately 1.7 Mb from the qter, by TEL array; SNP array data refine this breakpoint to within a gap between BACs on the TEL array (i.e., between RP11-93B14 and proximal BAC RP11-765G16).
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Mosaic paternal uniparental (iso)disomy for Chromosome 20 associated with multiple anomalies.
American journal of medical genetics. Part A, 2004Co-Authors: Charles P Venditti, Piper Hunt, Alan Donnenfeld, Elaine Zackai, Nancy B SpinnerAbstract:Uniparental disomy for a number of human Chromosomes is associated with clinical abnormalities. We report a child with a complex chromosomal rearrangement involving Chromosome 20 (45,XY,psu dic (20;20)(p13;p13)) and paternal uniparental isodisomy for Chromosome 20 in peripheral blood and bone marrow. This patient had multiple congenital abnormalities including microtia/anotia, micrencephaly, congenital heart disease, neuronal subependymal heterotopias, and colonic agangliosis. Molecular studies on DNA from peripheral blood demonstrated paternal uniparental inheritance of Chromosome 20. However, fibroblasts demonstrated a mosaic karyotype, with one cell line having 45 Chromosomes, including the pseudodicentric Chromosome 20 (75% of cells), and a second cell line having 46 Chromosomes, including the pseudodicentric Chromosome 20, and a normal Chromosome 20 (trisomy 20) (25% of cells). FISH experiments using a sub-telomeric probe that maps approximately 120 kb from the 20p telomere, showed that both copies of these sequences were present on the rearranged Chromosome, consistent with deletion of a very small interval. This leads us to suggest that in addition to trisomy 20 mosaicism, paternal uniparental disomy for Chromosome 20 could contribute to his clinical phenotype.
Aglaia Vignoli - One of the best experts on this subject based on the ideXlab platform.
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epilepsy in ring Chromosome 20 syndrome
Epilepsy Research, 2016Co-Authors: Aglaia Vignoli, Elena Zambrelli, Massimo Mastrangelo, Katherine Turner, Francesca Bisulli, Francesca Darra, Carmen Barba, Lucio Giordano, V Chiesa, Stefania BovaAbstract:Objective Ring Chromosome 20 syndrome is characterized by severe, drug resistant childhood onset epilepsy, often accompanied by cognitive impairment. We characterized the electro-clinical phenotype and the long-term course of epilepsy in a large series. Methods We reviewed the electro-clinical phenotype of 25 patients (aged 8-59 years), and assessed the relationship between epilepsy severity and clinical and/or genetic variables. We also searched for reports of patients diagnosed with r(20) syndrome in the literature, included those whose clinical information was sufficiently accurate, and compared their clinical features with the ones of our patients. Results Epilepsy exhibited an age dependent course. When seizure onset occurred in childhood (21 patients), terrifying hallucinations associated with focal motor seizures, often sleep-related (8 patients), or dyscognitive seizures (13 patients), were prominent features, often evolving into epileptic encephalopathy associated with non-convulsive status epilepticus (11 patients). In the long-term, progressive stabilization of drug resistant epilepsy associated with non-convulsive status epilepticus, focal seizures with motor and autonomic features, and eyelid myoclonia were noticed. Epilepsy onset in adolescence (3 patients) was accompanied by a milder developmental course, dyscognitive seizures and non-convulsive status epilepticus, and no cognitive decline. Only three older patients became seizure free (>5 years) We found statistically significant correlations between age at epilepsy onset and cognitive level. Although in the study cohort the relationship between r(20) ratio, age at epilepsy onset and cognitive level was non-statistically significant, it reached significance evaluating the larger cohort of patients previously published. Significance In ring(20) syndrome, epilepsy has an age dependent course and a worse outcome when age at seizure onset is earlier. The r(20) ratio and severity of cognitive impairment appear to be directly related to each other and inversely correlated with the age at epilepsy onset.
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sleep in ring Chromosome 20 syndrome a peculiar electroencephalographic pattern
Functional Neurology, 2013Co-Authors: Elena Zambrelli, Aglaia Vignoli, Lino Nobili, Giuseppe Didato, Massimo Mastrangelo, Katherine Turner, Maria Paola CaneviniAbstract:Ring Chromosome 20 [r(20)] syndrome is a chromosomal disorder characterized by epilepsy and intellectual disability. Distinctive electroclinical features and wakefulness EEG patterns have been described. The EEG features of sleep have not yet been evaluated. We studied the pattern of sleep in six patients aged 2-59 years who underwent at least one polysomnographic recording. Their sleep pattern evolution is described as deterioration ranging from normal to destructured NREM/REM sleep. NREM sleep alterations were observed from childhood and were more evident in adulthood. EEG abnormalities detected during wakefulness persisted, with morphological changes, during sleep. During NREM sleep all the subjects presented high amplitude delta sequences with a sharply contoured or notched appearance, prevalent over frontal regions. The theta rhythm of wakefulness was seen to persist during REM sleep. Ring Chromosome 20 syndrome shows sleep alterations that seem to be age-related. A potential role of cortical and thalamocortical dysfunction is discussed.
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ring Chromosome 20
European Journal of Medical Genetics, 2012Co-Authors: Robert Daber, Laura K Conlin, Laura D Leonard, Maria Paola Canevini, Aglaia Vignoli, Syed A Hosain, Lawrence W Brown, Nancy B SpinnerAbstract:Ring Chromosome 20 syndrome is a rare chromosomal disorder characterized by refractory epilepsy, with seizures in wakefulness and sleep, behavioral problems and mild to severe cognitive impairment. Facial dysmorphism or other congenital malformations are rarely reported making it difficult to diagnose the syndrome based on clinical findings alone. Therefore, diagnosis requires cytogenetic testing. More than 100 cases have been published since the initial report in 1972. In some patients, the ring (20) is found in all cells analyzed and in these cases, the ring is almost always accompanied by deletions of 20pter and/or 20qter. However, in the majority of cases the ring is present in only a proportion of cells, with two normal 20's in the remaining cells (mosaicism), and in these cases, no deletions of Chromosome 20 have been observed. Patients with supernumerary r(20) Chromosomes have also been identified, but these individuals do not generally have seizures and are not discussed in this review. Characterization by fluorescence in situ hybridization and array-based analysis has shed insight into the molecular composition and possible mechanisms of ring formation, in both the mosaic and non-mosaic patients. The age of onset of seizures correlates with the percentage of cells with the ring in mosaic patients. While the underlying etiology of the phenotype is still not understood, evidence is accumulating which suggests the deletion of candidate genes on Chromosome 20 is not responsible. Cytogenetic analysis, rather than chromosomal microarray analysis is recommended for diagnosis of this syndrome, as the mosaic cases do not have copy number alterations and are therefore not identified by array-based analysis.
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Chromosome 20 ring a chromosomal disorder associated with a particular electroclinical pattern
Epilepsia, 1998Co-Authors: Maria Paola Canevini, Aglaia Vignoli, V Sgro, Orsetta Zuffardi, R Canger, Romeo Carrozzo, Elena Rossi, David H Ledbetter, Fabio Minicucci, A PiazziniAbstract:Summary: Purpose: The Chromosome 20 ring [r(20)] is a rare chromosomal disorder without clear phenotypical markers. We describe the electroclinical pattern in a group of patients with r(20). Methods: We observed 3 patients (a boy, patient 1; his mother, patient 2; and an unrelated man, patient 3), performing prolonged video-EEG and cytogenetic studies and fluorescent in situ hybridization (FISH) with Chromosome-specific telomeric probes. Results: All 3 patients had a very similar abnormal electroclinical pattern characterized by long bursts or trains of rhythmic theta waves, which were sharply contoured or had a notched appearance (with no detectable clinical correlate), and generalized spike waves (SW) associated with seizures of probable frontotemporal origin (SFT). In all 3 patients, the cytogenetic analysis of T lymphocytes showed mosaicism with a normal cell line and a second cell line with a Chromosome 20, although the latter was little represented in patients 2 and 3. A few cells with a single Chromosome 20 were also found. The same cytogenetic findings were confirmed in the lymphoblastoid cell line of patient 1 and in the fibroblasts of patient 3. FISH with Chromosome-specific telomeric probes and TTAGGG sequences demonstrated the integrity of the ring Chromosomes. Conclusions: The clinical picture of these patients appears to be related to the instability of the r(20)-generating cells monosomic for Chromosome 20 and is thus haploinsufficient for a gene. In these patients, the electroclinical pattern of theta waves (probably unrelated to epilepsy) and the SW and SFT, even with mild mental retardation (MR) or no MR and without dysmorphic features, suggest that the r(20) syndrome may be present.
Laura K Conlin - One of the best experts on this subject based on the ideXlab platform.
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ring Chromosome 20
European Journal of Medical Genetics, 2012Co-Authors: Robert Daber, Laura K Conlin, Laura D Leonard, Maria Paola Canevini, Aglaia Vignoli, Syed A Hosain, Lawrence W Brown, Nancy B SpinnerAbstract:Ring Chromosome 20 syndrome is a rare chromosomal disorder characterized by refractory epilepsy, with seizures in wakefulness and sleep, behavioral problems and mild to severe cognitive impairment. Facial dysmorphism or other congenital malformations are rarely reported making it difficult to diagnose the syndrome based on clinical findings alone. Therefore, diagnosis requires cytogenetic testing. More than 100 cases have been published since the initial report in 1972. In some patients, the ring (20) is found in all cells analyzed and in these cases, the ring is almost always accompanied by deletions of 20pter and/or 20qter. However, in the majority of cases the ring is present in only a proportion of cells, with two normal 20's in the remaining cells (mosaicism), and in these cases, no deletions of Chromosome 20 have been observed. Patients with supernumerary r(20) Chromosomes have also been identified, but these individuals do not generally have seizures and are not discussed in this review. Characterization by fluorescence in situ hybridization and array-based analysis has shed insight into the molecular composition and possible mechanisms of ring formation, in both the mosaic and non-mosaic patients. The age of onset of seizures correlates with the percentage of cells with the ring in mosaic patients. While the underlying etiology of the phenotype is still not understood, evidence is accumulating which suggests the deletion of candidate genes on Chromosome 20 is not responsible. Cytogenetic analysis, rather than chromosomal microarray analysis is recommended for diagnosis of this syndrome, as the mosaic cases do not have copy number alterations and are therefore not identified by array-based analysis.
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ring Chromosome 20 epilepsy syndrome an overview
Journal of Pediatric Epilepsy, 2012Co-Authors: Syed A Hosain, Laura K Conlin, Nancy B SpinnerAbstract:The ring Chromosome 20 [r(20)], epilepsy syndrome is a relatively under-diagnosed epilepsy syndrome that has a striking association with seizures, which is not seen with other morphological aberrations of Chromosome 20. This syndrome is characterized by medically intractable complex partial epilepsy, subtle nocturnal frontal seizures, behavioral problems and mild mental impairment. In contrast to other epilepsy syndromes with chromosomal aberrations, dysmorphism (major or minor congenital malformations) and developmental delays are rarely reported. This lack of dysmorhism and relatively normal development in early life leads to delay in diagnosis. Additionally chromosomal testing is rarely considered in a patient with severe early onset epilepsy who does not have dysmorphic features, but this is the usual phenotype of r(20) epilepsy syndrome. More than 60 cases of r(20) have been reported in the literature. To date there is still no published data on the incidence and prevalence of this syndrome. This disorder appears to be pan-ethnic and non-gender specific. Cases of this syndrome have been identified in different parts of the world involving different ethnicities. Epilepsy in r(20) is often intractable with frontal lobe features. Non-convulsive status epilepticus and nocturnal seizures are frequently noted as are frontal lobe epileptiform electroencephalography abnormalities. Structural brain imaging is normal in most cases and is non-contributory. Definitive diagnosis can only be made by chromosomal analysis with mosaic screening. With more widespread cytogenetic chromosomal karyotyping in non-etiological cases of epilepsy, more cases of r(20) will undoubtedly be recognized.
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molecular analysis of ring Chromosome 20 syndrome reveals two distinct groups of patients
Journal of Medical Genetics, 2011Co-Authors: Laura K Conlin, Syed A Hosain, Samuel F Berkovic, Whitney Kramer, Anne L Hutchinson, Harold Riethman, Hakon Hakonarson, John C Mulley, Ingrid E Scheffer, Nancy B SpinnerAbstract:Background The ring Chromosome 20 syndrome (R20) is a rare genetic disorder associated with a refractory electroclinical epilepsy syndrome and variably expressed comorbidities of intellectual disability and dysmorphism. Methods To understand the structure and composition of the ring Chromosome 20 (r(20)) in this patient cohort, blood specimens from 28 affected individuals were analysed by cytogenetic, fluorescence in situ hybridisation, and/or high resolution whole genome single nucleotide polymorphism array analysis. Results These studies revealed two distinct groups of patients. Group 1 (N=21) was mosaic for the r(20) and a normal cell line with no detectable deletions or duplications of Chromosome 20 in either cell line. The mosaic nature of these rings suggests a postzygotic origin with formation of the ring by fusion of the telomeric regions with no apparent loss of subtelomeric or telomeric DNA. Group 2 (N=7) had non-mosaic ring Chromosomes with a deletion at one or both ends of the Chromosome, near the ring fusion point. The non-mosaic nature of these rings is consistent with a meiotic origin. The age of onset of seizures was significantly lower in the non-mosaic patients (group 2, median age of onset 2.1 years) than in the mosaic patients (group 1, median age of onset 6.0 years). Patients from group 2 had more extensive comorbidities. Conclusions These studies demonstrate that r(20) is molecularly heterogeneous and formed by two distinct mechanisms, which, in turn, produce different phenotypic spectrums.
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two siblings with alternate unbalanced recombinants derived from a large cryptic maternal pericentric inversion of Chromosome 20
American Journal of Medical Genetics Part A, 2010Co-Authors: Cheryl Descipio, Laura K Conlin, Nancy B Spinner, Harold Riethman, Jennifer J D Morrissette, Dinah Clark, Maninder Kaur, James Coplan, Ian D KrantzAbstract:: Two brothers, with dissimilar clinical features, were each found to have different abnormalities of Chromosome 20 by subtelomere fluorescence in situ hybridization (FISH). The proband had deletion of 20p subtelomere and duplication of 20q subtelomere, while his brother was found to have a duplication of 20p subtelomere and deletion of 20q subtelomere. Parental cytogenetic studies were initially thought to be normal, both by G-banding and by subtelomere FISH analysis. Since Chromosome 20 is a metacentric Chromosome and an inversion was suspected, we used anchored FISH to assist in identifying a possible inversion. This approach employed concomitant hybridization of a FISH probe to the short (p) arm of Chromosome 20 with the 20q subtelomere probe. We identified a cytogenetically non-visible, mosaic pericentric inversion of one of the maternal Chromosome 20 homologs, providing a mechanistic explanation for the chromosomal abnormalities present in these brothers. Array comparative genomic hybridization (CGH) with both a custom-made BAC and cosmid-based subtelomere specific array (TEL array) and a commercially available SNP-based array confirmed and further characterized these rearrangements, identifying this as the largest pericentric inversion of Chromosome 20 described to date. TEL array data indicate that the 20p breakpoint is defined by BAC RP11-978M13, approximately 900 kb from the pter; SNP array data reveal this breakpoint to occur within BAC RP11-978M13. The 20q breakpoint is defined by BAC RP11-93B14, approximately 1.7 Mb from the qter, by TEL array; SNP array data refine this breakpoint to within a gap between BACs on the TEL array (i.e., between RP11-93B14 and proximal BAC RP11-765G16).
Mark Leppert - One of the best experts on this subject based on the ideXlab platform.
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Seizure characteristics in Chromosome 20 benign familial neonatal convulsions
Neurology, 1993Co-Authors: Gabriel M. Ronen, Teodoro O. Rosales, Mary B Connolly, V E Anderson, Mark LeppertAbstract:We studied a kindred of 69 affected individuals with the autosomal dominant epileptic syndrome of benign familial neonatal convulsions, linked to Chromosome 20. Forty-two percent had their seizure onset on day 3, while remission took place in 68% during the first 6 weeks. Seizures were brief and the phenotype was of a mixed seizure type, starting with tonic posture, ocular symptoms, apnea, and other autonomic features. The seizure often progressed to clonic movements and motor automatisms. The postictal state was brief, and interictally the neonates looked well. The ictal EEG pattern with generalized suppression of amplitude on onset may be relatively unique. Neurocognitive outcome was usually normal, but the risk for subsequent epilepsy was 16%. Most of the later epilepsy was generalized tonic or tonic-clonic, and some seizures were provoked, raising the possibility of an unusual form of reflex epilepsy.
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Seizure characteristics in Chromosome 20 benign familial neonatal convulsions
Neurology, 1993Co-Authors: Gabriel M. Ronen, Teodoro O. Rosales, Mary B Connolly, V E Anderson, Mark LeppertAbstract:We studied a kindred of 69 affected individuals with the autosomal dominant epileptic syndrome of benign familial neonatal convulsions, linked to Chromosome 20. Forty-two percent had their seizure onset on day 3, while remission took place in 68% during the first 6 weeks. Seizures were brief and the phenotype was of a mixed seizure type, starting with tonic posture, ocular symptoms, apnea, and other autonomic features. The seizure often progressed to clonic movements and motor automatisms. The postictal state was brief, and interictally the neonates looked well. The ictal EEG pattern with generalized suppression of amplitude on onset may be relatively unique. Neurocognitive outcome was usually normal, but the risk for subsequent epilepsy was 16%. Most of the later epilepsy was generalized tonic or tonic-clonic, and some seizures were provoked, raising the possibility of an unusual form of reflex epilepsy.
Maria Paola Canevini - One of the best experts on this subject based on the ideXlab platform.
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sleep in ring Chromosome 20 syndrome a peculiar electroencephalographic pattern
Functional Neurology, 2013Co-Authors: Elena Zambrelli, Aglaia Vignoli, Lino Nobili, Giuseppe Didato, Massimo Mastrangelo, Katherine Turner, Maria Paola CaneviniAbstract:Ring Chromosome 20 [r(20)] syndrome is a chromosomal disorder characterized by epilepsy and intellectual disability. Distinctive electroclinical features and wakefulness EEG patterns have been described. The EEG features of sleep have not yet been evaluated. We studied the pattern of sleep in six patients aged 2-59 years who underwent at least one polysomnographic recording. Their sleep pattern evolution is described as deterioration ranging from normal to destructured NREM/REM sleep. NREM sleep alterations were observed from childhood and were more evident in adulthood. EEG abnormalities detected during wakefulness persisted, with morphological changes, during sleep. During NREM sleep all the subjects presented high amplitude delta sequences with a sharply contoured or notched appearance, prevalent over frontal regions. The theta rhythm of wakefulness was seen to persist during REM sleep. Ring Chromosome 20 syndrome shows sleep alterations that seem to be age-related. A potential role of cortical and thalamocortical dysfunction is discussed.
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ring Chromosome 20
European Journal of Medical Genetics, 2012Co-Authors: Robert Daber, Laura K Conlin, Laura D Leonard, Maria Paola Canevini, Aglaia Vignoli, Syed A Hosain, Lawrence W Brown, Nancy B SpinnerAbstract:Ring Chromosome 20 syndrome is a rare chromosomal disorder characterized by refractory epilepsy, with seizures in wakefulness and sleep, behavioral problems and mild to severe cognitive impairment. Facial dysmorphism or other congenital malformations are rarely reported making it difficult to diagnose the syndrome based on clinical findings alone. Therefore, diagnosis requires cytogenetic testing. More than 100 cases have been published since the initial report in 1972. In some patients, the ring (20) is found in all cells analyzed and in these cases, the ring is almost always accompanied by deletions of 20pter and/or 20qter. However, in the majority of cases the ring is present in only a proportion of cells, with two normal 20's in the remaining cells (mosaicism), and in these cases, no deletions of Chromosome 20 have been observed. Patients with supernumerary r(20) Chromosomes have also been identified, but these individuals do not generally have seizures and are not discussed in this review. Characterization by fluorescence in situ hybridization and array-based analysis has shed insight into the molecular composition and possible mechanisms of ring formation, in both the mosaic and non-mosaic patients. The age of onset of seizures correlates with the percentage of cells with the ring in mosaic patients. While the underlying etiology of the phenotype is still not understood, evidence is accumulating which suggests the deletion of candidate genes on Chromosome 20 is not responsible. Cytogenetic analysis, rather than chromosomal microarray analysis is recommended for diagnosis of this syndrome, as the mosaic cases do not have copy number alterations and are therefore not identified by array-based analysis.
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Chromosome 20 ring a chromosomal disorder associated with a particular electroclinical pattern
Epilepsia, 1998Co-Authors: Maria Paola Canevini, Aglaia Vignoli, V Sgro, Orsetta Zuffardi, R Canger, Romeo Carrozzo, Elena Rossi, David H Ledbetter, Fabio Minicucci, A PiazziniAbstract:Summary: Purpose: The Chromosome 20 ring [r(20)] is a rare chromosomal disorder without clear phenotypical markers. We describe the electroclinical pattern in a group of patients with r(20). Methods: We observed 3 patients (a boy, patient 1; his mother, patient 2; and an unrelated man, patient 3), performing prolonged video-EEG and cytogenetic studies and fluorescent in situ hybridization (FISH) with Chromosome-specific telomeric probes. Results: All 3 patients had a very similar abnormal electroclinical pattern characterized by long bursts or trains of rhythmic theta waves, which were sharply contoured or had a notched appearance (with no detectable clinical correlate), and generalized spike waves (SW) associated with seizures of probable frontotemporal origin (SFT). In all 3 patients, the cytogenetic analysis of T lymphocytes showed mosaicism with a normal cell line and a second cell line with a Chromosome 20, although the latter was little represented in patients 2 and 3. A few cells with a single Chromosome 20 were also found. The same cytogenetic findings were confirmed in the lymphoblastoid cell line of patient 1 and in the fibroblasts of patient 3. FISH with Chromosome-specific telomeric probes and TTAGGG sequences demonstrated the integrity of the ring Chromosomes. Conclusions: The clinical picture of these patients appears to be related to the instability of the r(20)-generating cells monosomic for Chromosome 20 and is thus haploinsufficient for a gene. In these patients, the electroclinical pattern of theta waves (probably unrelated to epilepsy) and the SW and SFT, even with mild mental retardation (MR) or no MR and without dysmorphic features, suggest that the r(20) syndrome may be present.