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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. Assessment of efficacy of treatment. A tool for patient self-assessment of the effect of treatment on social and mental health aspects of the disorder has been proposed .Agents/Circumstances to AvoidThe following should be avoided:Foods with a high content of precursors of trimethylamine or inhibitors of FMO3 enzyme activity, including seafood (fish, cephalopods, and crustaceans), eggs, offal, legumes, brassicas, and soya products. Avoid or eat in moderation.Food supplements and "health" foods that contain high doses of the trimethylamine precursors choline and lecithinDrugs that are metabolized by the FMO3 enzyme; for example, the antipsychotic clozapine; the monoamine oxidase B inhibitor deprenyl; the anti-histamine ranitidine; the anti-estrogen tamoxifen; and the nonsteroidal anti-inflammatories benzydamine and sulindac . These compete for residual FMO3 activity. As well as exacerbating the condition, reduced metabolism of the drug may | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. eat in moderation.Food supplements and "health" foods that contain high doses of the trimethylamine precursors choline and lecithinDrugs that are metabolized by the FMO3 enzyme; for example, the antipsychotic clozapine; the monoamine oxidase B inhibitor deprenyl; the anti-histamine ranitidine; the anti-estrogen tamoxifen; and the nonsteroidal anti-inflammatories benzydamine and sulindac . These compete for residual FMO3 activity. As well as exacerbating the condition, reduced metabolism of the drug may cause adverse effects.Factors that promote sweating (e.g., exercise, stress, emotional upsets)Evaluation of Relatives at RiskSee Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.Pregnancy ManagementCholine, which is essential for nerve and brain development in the fetus, should not be over-restricted in pregnant women with primary trimethylaminuria.Therapies Under InvestigationSearch ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1103/ | 35RYEZ4 | Primary Trimethylaminuria | C0342739 | 3 | primary trimethylaminuria. , reduced metabolism of the drug may cause adverse effects.Factors that promote sweating (e.g., exercise, stress, emotional upsets)Evaluation of Relatives at RiskSee Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.Pregnancy ManagementCholine, which is essential for nerve and brain development in the fetus, should not be over-restricted in pregnant women with primary trimethylaminuria.Therapies Under InvestigationSearch ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. SummaryClinical characteristics.Progressive myoclonic epilepsy type 1(EPM1) is a neurodegenerative disorder characterized by onset from age six to 15 years, stimulus-sensitive myoclonus, and tonic-clonic epileptic seizures. Some years after the onset, ataxia, incoordination, intentional tremor, and dysarthria develop. Individuals with EPM1 are cognitively mostly within the normal range, but show emotional lability and depression. The epileptic seizures are usually well controlled by antiseizure medications, but the myoclonic jerks are progressive, action activated, and treatment resistant, and can be severely disabling.Diagnosis/testing.The diagnosis of EPM1 is established in a proband with suggestive findings and either biallelic abnormal CCC-CGC-CCC-GCG dodecamer repeat expansions in CSTB or compound heterozygosity for a CSTB dodecamer repeat expansion and a CSTB sequence variant (i.e., single-nucleotide variant or indel) | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. controlled by antiseizure medications, but the myoclonic jerks are progressive, action activated, and treatment resistant, and can be severely disabling.Diagnosis/testing.The diagnosis of EPM1 is established in a proband with suggestive findings and either biallelic abnormal CCC-CGC-CCC-GCG dodecamer repeat expansions in CSTB or compound heterozygosity for a CSTB dodecamer repeat expansion and a CSTB sequence variant (i.e., single-nucleotide variant or indel) identified by molecular genetic testing.Management.Treatment of manifestations: Symptomatic pharmacologic and rehabilitative management, including psychosocial support, are the mainstay of care; valproic acid, the first drug of choice, diminishes myoclonus and the frequency of generalized seizures; clonazepam, approved by FDA for the treatment of myoclonic seizures, is an add-on therapy; high-dose piracetam is used to treat myoclonus; levetiracetam, brivaracetam, | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. , single-nucleotide variant or indel) identified by molecular genetic testing.Management.Treatment of manifestations: Symptomatic pharmacologic and rehabilitative management, including psychosocial support, are the mainstay of care; valproic acid, the first drug of choice, diminishes myoclonus and the frequency of generalized seizures; clonazepam, approved by FDA for the treatment of myoclonic seizures, is an add-on therapy; high-dose piracetam is used to treat myoclonus; levetiracetam, brivaracetam, and perampanel appear to be effective for both myoclonus and generalized seizures. Topiramate and zonisamide may also be used as add-on therapy.Surveillance: Lifelong clinical follow up including evaluation of drug treatment and rehabilitation.Agents/circumstances to avoid: Phenytoin aggravates neurologic symptoms or even accelerates cerebellar degeneration; sodium channel blockers (carbamazepine, oxcarbazepine), GABAergic drugs (tiagabine, vigabatrin), and gabapentin | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. cetam, brivaracetam, and perampanel appear to be effective for both myoclonus and generalized seizures. Topiramate and zonisamide may also be used as add-on therapy.Surveillance: Lifelong clinical follow up including evaluation of drug treatment and rehabilitation.Agents/circumstances to avoid: Phenytoin aggravates neurologic symptoms or even accelerates cerebellar degeneration; sodium channel blockers (carbamazepine, oxcarbazepine), GABAergic drugs (tiagabine, vigabatrin), and gabapentin and pregabalin may aggravate myoclonus and myoclonic seizures.Genetic counseling.EPM1 is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once both CSTB pathogenic variants in a family are known, carrier testing for at-risk relatives, prenatal testing for pregnancies | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. e, vigabatrin), and gabapentin and pregabalin may aggravate myoclonus and myoclonic seizures.Genetic counseling.EPM1 is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once both CSTB pathogenic variants in a family are known, carrier testing for at-risk relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible.DiagnosisSuggestive FindingsThe diagnosis of progressive myoclonic epilepsy type 1 (EPM1) is suspected in a previously healthy child age six to 15 years who manifests the following:Involuntary, action-activated myoclonic jerks AND/OR generalized tonic-clonic seizuresPhotosensitive, generalized spike-and-wave and polyspike-and-wave paroxysms on EEGAbnor | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. at-risk relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible.DiagnosisSuggestive FindingsThe diagnosis of progressive myoclonic epilepsy type 1 (EPM1) is suspected in a previously healthy child age six to 15 years who manifests the following:Involuntary, action-activated myoclonic jerks AND/OR generalized tonic-clonic seizuresPhotosensitive, generalized spike-and-wave and polyspike-and-wave paroxysms on EEGAbnormal EEG (always abnormal, even before the onset of manifestations). The background activity is labile and may be slower than normal. Photosensitivity is marked.A gradual worsening of the neurologic manifestations (myoclonus and ataxia), difficulties running, playing sports, using stairsNormal brain MRIEstablishing the DiagnosisThe diagnosis of EPM1 disease is established in a proband with suggestive findings and either biallelic abnormal CCC-CGC-CCC-GC | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. -wave paroxysms on EEGAbnormal EEG (always abnormal, even before the onset of manifestations). The background activity is labile and may be slower than normal. Photosensitivity is marked.A gradual worsening of the neurologic manifestations (myoclonus and ataxia), difficulties running, playing sports, using stairsNormal brain MRIEstablishing the DiagnosisThe diagnosis of EPM1 disease is established in a proband with suggestive findings and either biallelic abnormal CCC-CGC-CCC-GCG dodecamer repeat expansions in CSTB or compound heterozygosity for a CSTB dodecamer repeat expansion and a CSTB sequence variant (i.e., single-nucleotide variant or indel) identified by molecular genetic testing (see Table 1).Note: Pathogenic dodecamer repeat expansions in CSTB
cannot be detected by sequence-based multigene panels, exome sequencing, or genome sequencing.Repeat sizesNormal. 2 to 3 dodecamer repeats | [
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] |
gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. abnormal CCC-CGC-CCC-GCG dodecamer repeat expansions in CSTB or compound heterozygosity for a CSTB dodecamer repeat expansion and a CSTB sequence variant (i.e., single-nucleotide variant or indel) identified by molecular genetic testing (see Table 1).Note: Pathogenic dodecamer repeat expansions in CSTB
cannot be detected by sequence-based multigene panels, exome sequencing, or genome sequencing.Repeat sizesNormal. 2 to 3 dodecamer repeatsUncertain significance. 12-17 dodecamer repeats (unstable, but not clinically characterized)Pathogenic (full penetrance). ≥30 dodecamer repeatsNote: The dodecamer repeat sequence is CCC-CGC-CCC-GCG. Repeats of 4-11 and 18-29 have not been observed.Molecular genetic testing relies on targeted analysis to characterize the number of CSTB CCC-CGC-CCC-GCG dodecamer repeats (see | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. rmal. 2 to 3 dodecamer repeatsUncertain significance. 12-17 dodecamer repeats (unstable, but not clinically characterized)Pathogenic (full penetrance). ≥30 dodecamer repeatsNote: The dodecamer repeat sequence is CCC-CGC-CCC-GCG. Repeats of 4-11 and 18-29 have not been observed.Molecular genetic testing relies on targeted analysis to characterize the number of CSTB CCC-CGC-CCC-GCG dodecamer repeats (see Table 7).Table 1. Molecular Genetic Testing Used in Progressive Myoclonic Epilepsy Type 1View in own windowGene 1Method 2, 3Proportion of Probands with a Pathogenic Variant Detectable by MethodCSTBTargeted analysis for the dodecamer expansion~90% 4, 5Sequence analysis 6~10% 41. See Table A. Genes and Databases for chromosome locus and protein.2. See Table 7 for specific methods to characterize the number of | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. CCC-GCG dodecamer repeats (see Table 7).Table 1. Molecular Genetic Testing Used in Progressive Myoclonic Epilepsy Type 1View in own windowGene 1Method 2, 3Proportion of Probands with a Pathogenic Variant Detectable by MethodCSTBTargeted analysis for the dodecamer expansion~90% 4, 5Sequence analysis 6~10% 41. See Table A. Genes and Databases for chromosome locus and protein.2. See Table 7 for specific methods to characterize the number of dodecamer (CCC-CGC-CCC-GCG) repeats in CSTB.3. Sequence-based multigene panels, exome sequencing, and genome sequencing cannot detect pathogenic repeat expansions in this gene.4. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole- | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. 7 for specific methods to characterize the number of dodecamer (CCC-CGC-CCC-GCG) repeats in CSTB.3. Sequence-based multigene panels, exome sequencing, and genome sequencing cannot detect pathogenic repeat expansions in this gene.4. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.5. Lalioti et al , Joensuu et al 6. ~99% in Finnish individuals Clinical CharacteristicsClinical DescriptionIn more than half of individuals with progressive myoclonic epilepsy type 1 (EPM1) the first manifestation is involuntary myoclonic jerks . The myoclonic jerks are action activated and stimulus sensitive and may be provoked | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.5. Lalioti et al , Joensuu et al 6. ~99% in Finnish individuals Clinical CharacteristicsClinical DescriptionIn more than half of individuals with progressive myoclonic epilepsy type 1 (EPM1) the first manifestation is involuntary myoclonic jerks . The myoclonic jerks are action activated and stimulus sensitive and may be provoked by light, physical exertion, and stress. They occur predominantly in the proximal muscles of the extremities and are asynchronous; they may be focal or multifocal and may generalize to a series of myoclonic seizures or even status myoclonicus (continuous myoclonic jerks involving a semi-loss of consciousness).During the first five to ten years, the symptoms/myoclonic jerks characteristically progress and about one third of affected individuals become severely incapacita | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. action activated and stimulus sensitive and may be provoked by light, physical exertion, and stress. They occur predominantly in the proximal muscles of the extremities and are asynchronous; they may be focal or multifocal and may generalize to a series of myoclonic seizures or even status myoclonicus (continuous myoclonic jerks involving a semi-loss of consciousness).During the first five to ten years, the symptoms/myoclonic jerks characteristically progress and about one third of affected individuals become severely incapacitated (wheelchair bound). Although the myoclonic jerks are disabling and resistant to therapy, the individual usually learns to tolerate them over time, if psychosocial support is good and depression not too severe.In almost half of individuals, the first manifestation is tonic-clonic seizures. There may also be absence, psychomotor, and/or focal motor seizures. Epileptic seizures, infrequent in the early stages of the disease, often increase in frequency during the ensuing | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. third of affected individuals become severely incapacitated (wheelchair bound). Although the myoclonic jerks are disabling and resistant to therapy, the individual usually learns to tolerate them over time, if psychosocial support is good and depression not too severe.In almost half of individuals, the first manifestation is tonic-clonic seizures. There may also be absence, psychomotor, and/or focal motor seizures. Epileptic seizures, infrequent in the early stages of the disease, often increase in frequency during the ensuing three to seven years. Later they may cease entirely with appropriate antiepileptic drug treatment. In rare cases, tonic-clonic seizures do not occur.Neurologic findings initially appear normal; however, experienced observers usually note recurrent, almost imperceptible myoclonus, especially in response to photic stimuli or other stimuli (threat, clapping of hands, nose tapping, reflexes) or to action (movements made during neurologic examination) or to cognitive stimuli (task demanding cognitive | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. disease, often increase in frequency during the ensuing three to seven years. Later they may cease entirely with appropriate antiepileptic drug treatment. In rare cases, tonic-clonic seizures do not occur.Neurologic findings initially appear normal; however, experienced observers usually note recurrent, almost imperceptible myoclonus, especially in response to photic stimuli or other stimuli (threat, clapping of hands, nose tapping, reflexes) or to action (movements made during neurologic examination) or to cognitive stimuli (task demanding cognitive and psychomotor processing). Some years after the onset, ataxia, incoordination, intentional tremor, and dysarthria develop.Cognitive performance, especially memory, is mostly within the normal range. However, affected individuals may exhibit poor performance in time-limited tests dependent on motor functions.The disease course is inevitably progressive; however, the rate of deterioration – especially in terms of walking capacity – appears to vary even within the same family. Generalized | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. ) or to cognitive stimuli (task demanding cognitive and psychomotor processing). Some years after the onset, ataxia, incoordination, intentional tremor, and dysarthria develop.Cognitive performance, especially memory, is mostly within the normal range. However, affected individuals may exhibit poor performance in time-limited tests dependent on motor functions.The disease course is inevitably progressive; however, the rate of deterioration – especially in terms of walking capacity – appears to vary even within the same family. Generalized tonic-clonic seizures are usually controlled with treatment, but myoclonic jerks may become severe, appear in series, and inhibit normal activities . Myoclonic jerks may also be subcortical in origin and therefore difficult to control . The individual becomes depressed and progression ensues. Education is often interrupted because of emotional, social, and intellectual problems.In the past, life span was shortened; many individuals died eight to 15 years after the onset of disease, usually | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. to vary even within the same family. Generalized tonic-clonic seizures are usually controlled with treatment, but myoclonic jerks may become severe, appear in series, and inhibit normal activities . Myoclonic jerks may also be subcortical in origin and therefore difficult to control . The individual becomes depressed and progression ensues. Education is often interrupted because of emotional, social, and intellectual problems.In the past, life span was shortened; many individuals died eight to 15 years after the onset of disease, usually before age 30 years. With better pharmacologic, physiotherapeutic, and psychosocial supportive treatment, life expectancy is comparable to controls up to age 40 years, but is poorer over the long term. Death occurs mainly due to respiratory infections .Genotype-Phenotype CorrelationsIndividuals with pathogenic variants in CSTB usually develop similar disease manifestations. There is evidence that correlation exists between the length of the expanded dodecamer repeat and the age of onset or disease severity . However, disease severity | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. 15 years after the onset of disease, usually before age 30 years. With better pharmacologic, physiotherapeutic, and psychosocial supportive treatment, life expectancy is comparable to controls up to age 40 years, but is poorer over the long term. Death occurs mainly due to respiratory infections .Genotype-Phenotype CorrelationsIndividuals with pathogenic variants in CSTB usually develop similar disease manifestations. There is evidence that correlation exists between the length of the expanded dodecamer repeat and the age of onset or disease severity . However, disease severity also varies among affected individuals within a family with apparently similar repeat-size expansions.Moreover, EPM1 resulting from compound heterozygosity for a dodecamer repeat expansion and a sequence variant (i.e., single-nucleotide variant or indel) often presents with earlier age of onset, more severe myoclonus, and seizures that may be drug resistant . It has been also suggested that compound heterozygosity causes a more severe EPM1 phenotype in affected males than females, but the | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. onset or disease severity . However, disease severity also varies among affected individuals within a family with apparently similar repeat-size expansions.Moreover, EPM1 resulting from compound heterozygosity for a dodecamer repeat expansion and a sequence variant (i.e., single-nucleotide variant or indel) often presents with earlier age of onset, more severe myoclonus, and seizures that may be drug resistant . It has been also suggested that compound heterozygosity causes a more severe EPM1 phenotype in affected males than females, but the numbers are small .Recently, homozygous stop-codon and frameshift pathogenic variants in CSTB were associated with infantile-onset progressive disorders with unexplained severe developmental delay, microcephaly, and hypomyelination . The incidence in Finland is estimated at 1:20,000 births.Differential DiagnosisAt the onset of progressive myoclonic epilepsy type 1 (EPM1), juvenile myoclonic epilepsy (JME) (OMIM PS254770) – which has | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. phenotype in affected males than females, but the numbers are small .Recently, homozygous stop-codon and frameshift pathogenic variants in CSTB were associated with infantile-onset progressive disorders with unexplained severe developmental delay, microcephaly, and hypomyelination . The incidence in Finland is estimated at 1:20,000 births.Differential DiagnosisAt the onset of progressive myoclonic epilepsy type 1 (EPM1), juvenile myoclonic epilepsy (JME) (OMIM PS254770) – which has a more favorable outcome – should be considered as a diagnostic alternative. Individuals with JME have a normal neurologic examination and undisturbed background of the EEG.Other disorders to consider in the differential diagnosis of EPM1 are summarized in Table 2.Table 2. Genes of Interest in the Differential Diagnosis of Progressive Myoclonic Epilepsy Type 1View in own windowGene(s)DisorderMOIClinical Characteristics of Differential Diagnosis DisorderOverlapping w/EPM1Dis | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. IM PS254770) – which has a more favorable outcome – should be considered as a diagnostic alternative. Individuals with JME have a normal neurologic examination and undisturbed background of the EEG.Other disorders to consider in the differential diagnosis of EPM1 are summarized in Table 2.Table 2. Genes of Interest in the Differential Diagnosis of Progressive Myoclonic Epilepsy Type 1View in own windowGene(s)DisorderMOIClinical Characteristics of Differential Diagnosis DisorderOverlapping w/EPM1Distinguishing from EPM1EPM2ANHLRC1PME, Lafora typeARPMEFocal occipital seizures & fragmentary, symmetric, or generalized myoclonus beginning in previously healthy individualsLater onset (age 8-19 yrs); rapid disease progression; death ~10 yrs after diagnosisPrior to the availability of molecular genetic testing, histologic findings on skin biopsy established the diagnosis.GOSR2EPM6 (OMIM 614018 | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. DisorderOverlapping w/EPM1Distinguishing from EPM1EPM2ANHLRC1PME, Lafora typeARPMEFocal occipital seizures & fragmentary, symmetric, or generalized myoclonus beginning in previously healthy individualsLater onset (age 8-19 yrs); rapid disease progression; death ~10 yrs after diagnosisPrior to the availability of molecular genetic testing, histologic findings on skin biopsy established the diagnosis.GOSR2EPM6 (OMIM 614018)AREarly-onset ataxia (average age 2 yrs) followed by action myoclonus & seizures later in childhoodIndependent ambulation lost in 2nd decadeEarlier onset; scoliosis (develops by adolescence)KCNC1EPM7 (OMIM 616187)ADResembles EPM1 at disease onset 1Presents at age 6-15 yrs w/myoclonus (sometimes reported as tremor)The later disease course is characterized by moderate- | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. EPM6 (OMIM 614018)AREarly-onset ataxia (average age 2 yrs) followed by action myoclonus & seizures later in childhoodIndependent ambulation lost in 2nd decadeEarlier onset; scoliosis (develops by adolescence)KCNC1EPM7 (OMIM 616187)ADResembles EPM1 at disease onset 1Presents at age 6-15 yrs w/myoclonus (sometimes reported as tremor)The later disease course is characterized by moderate-to-severe incapacitating myoclonus, infrequent tonic-clonic seizures, ataxia, & mild (if any) cognitive decline.EPM7 & EPM1 have a remarkably similar clinical presentation. EPM7 may have a somewhat more severe progression than EPM1 in its early phases.MT-TFMT-TIMT-TKMT-TL1MT-TPMERRFMatPMEOnset usually in childhood, after normal | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. The later disease course is characterized by moderate-to-severe incapacitating myoclonus, infrequent tonic-clonic seizures, ataxia, & mild (if any) cognitive decline.EPM7 & EPM1 have a remarkably similar clinical presentation. EPM7 may have a somewhat more severe progression than EPM1 in its early phases.MT-TFMT-TIMT-TKMT-TL1MT-TPMERRFMatPMEOnset usually in childhood, after normal early developmentBrain MRI often shows brain atrophy & basal ganglia calcification.Muscle biopsy typically shows RRF.SCARB2Action myoclonus - renal failure syndromeARTypically presents at ages 15-25 yrs; may present w/neurologic symptoms (e.g., tremor, action myoclonus, seizures, ataxia) 2May present w/proteinuria that progresses to renal failureAD = autosomal dominant; AR = autosomal recessive; Mat = maternal; MERRF = | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. MEOnset usually in childhood, after normal early developmentBrain MRI often shows brain atrophy & basal ganglia calcification.Muscle biopsy typically shows RRF.SCARB2Action myoclonus - renal failure syndromeARTypically presents at ages 15-25 yrs; may present w/neurologic symptoms (e.g., tremor, action myoclonus, seizures, ataxia) 2May present w/proteinuria that progresses to renal failureAD = autosomal dominant; AR = autosomal recessive; Mat = maternal; MERRF = myoclonic epilepsy with ragged red fibers; MOI = mode of inheritance; PME = progressive myoclonic epilepsy; RRF = ragged red fibers1. Muona et al 2. Action myoclonus - renal failure syndrome typically comprises a continuum of two major (and ultimately fatal) manifestations: progressive myoclonic epilepsy and renal failure; however, in some instances, the kidneys are not involved. Neurologic manifestations can appear before, simultaneously, or after the renal manifestations | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. ; Mat = maternal; MERRF = myoclonic epilepsy with ragged red fibers; MOI = mode of inheritance; PME = progressive myoclonic epilepsy; RRF = ragged red fibers1. Muona et al 2. Action myoclonus - renal failure syndrome typically comprises a continuum of two major (and ultimately fatal) manifestations: progressive myoclonic epilepsy and renal failure; however, in some instances, the kidneys are not involved. Neurologic manifestations can appear before, simultaneously, or after the renal manifestations.ManagementEvaluations Following Initial DiagnosisTo establish the extent of disease and needs in an individual diagnosed with progressive myoclonic epilepsy type 1 (EPM1), the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to the diagnosis) are recommended.Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with EPM1View in own windowSystem/ConcernEvaluationCommentNeurologicNeurologic assessment of myoclonus, | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. before, simultaneously, or after the renal manifestations.ManagementEvaluations Following Initial DiagnosisTo establish the extent of disease and needs in an individual diagnosed with progressive myoclonic epilepsy type 1 (EPM1), the evaluations summarized in Table 3 (if not performed as part of the evaluation that led to the diagnosis) are recommended.Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with EPM1View in own windowSystem/ConcernEvaluationCommentNeurologicNeurologic assessment of myoclonus, incl myoclonus at rest, w/action, & in response to stimuliUse standardized UMRS.Seizure type & frequencyObtain baseline EEG before initiation of antiseizure therapy (when EEG is most characteristic).Cerebellar motor dysfunction (gait & postural ataxia, dysmetria, dysdiadochokinesis, tremor, dysarthria, nystagmus, saccades & smooth pursuit)Use standardized scale to establish baseline | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. gicNeurologic assessment of myoclonus, incl myoclonus at rest, w/action, & in response to stimuliUse standardized UMRS.Seizure type & frequencyObtain baseline EEG before initiation of antiseizure therapy (when EEG is most characteristic).Cerebellar motor dysfunction (gait & postural ataxia, dysmetria, dysdiadochokinesis, tremor, dysarthria, nystagmus, saccades & smooth pursuit)Use standardized scale to establish baseline for ataxia (SARA, ICARS, or BARS).Musculoskeletal /Activities of dailylivingBy physical medicine & rehabilitation/OT/PTTo assess gross motor & fine motor skills, gait, ambulation, need for adaptive devices, need for ongoing PT/OTSpeechFor those w/dysarthria: speech & language evalConsider referral to speech & language pathologist.CognitiveNeuropsych | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. smooth pursuit)Use standardized scale to establish baseline for ataxia (SARA, ICARS, or BARS).Musculoskeletal /Activities of dailylivingBy physical medicine & rehabilitation/OT/PTTo assess gross motor & fine motor skills, gait, ambulation, need for adaptive devices, need for ongoing PT/OTSpeechFor those w/dysarthria: speech & language evalConsider referral to speech & language pathologist.CognitiveNeuropsychologistCognitive eval to establish baselinePsychiatricPsychiatristEvaluate as needed for depression & supportive therapy.Development /SchoolperformanceDevelopmental assessmentTo incl motor, adaptive, cognitive, & speech/language evalEvaluation for special educationGeneticcounselingBy genetics professionals 1To inform affected individuals & their families about the nature, MOI, & implications of EPM1 to facilitate medical | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. amp; language pathologist.CognitiveNeuropsychologistCognitive eval to establish baselinePsychiatricPsychiatristEvaluate as needed for depression & supportive therapy.Development /SchoolperformanceDevelopmental assessmentTo incl motor, adaptive, cognitive, & speech/language evalEvaluation for special educationGeneticcounselingBy genetics professionals 1To inform affected individuals & their families about the nature, MOI, & implications of EPM1 to facilitate medical & personal decision makingFamily support/resourcesAssess:
Use of community or online resources such as Parent to Parent and patient organizations;Need for social work involvement for parental support;Need for home nursing referral.To facilitate peer support for patients & familiesBARS = Brief Ataxia Rating Scale; ICARS = International Cooperative Ataxia Rating Scale; MOI = mode of inheritance; OT = occupational therapist/therapy; PT = physical therapist/ | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. amp; implications of EPM1 to facilitate medical & personal decision makingFamily support/resourcesAssess:
Use of community or online resources such as Parent to Parent and patient organizations;Need for social work involvement for parental support;Need for home nursing referral.To facilitate peer support for patients & familiesBARS = Brief Ataxia Rating Scale; ICARS = International Cooperative Ataxia Rating Scale; MOI = mode of inheritance; OT = occupational therapist/therapy; PT = physical therapist/therapy; SARA = Scale for the Assessment and Rating of Ataxia; UMRS = Unified Myoclonus Rating Scale1. Medical geneticist, certified genetic counselor, or certified advanced genetic nurseTreatment of ManifestationsTable 4. Treatment of Manifestations in Individuals with EPM1View in own windowManifestation/ConcernTreatmentConsiderations/OtherMyoclonusPharmacologicValproic acidFirst drug of choice; diminishes myoclonus & | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. therapist/therapy; PT = physical therapist/therapy; SARA = Scale for the Assessment and Rating of Ataxia; UMRS = Unified Myoclonus Rating Scale1. Medical geneticist, certified genetic counselor, or certified advanced genetic nurseTreatment of ManifestationsTable 4. Treatment of Manifestations in Individuals with EPM1View in own windowManifestation/ConcernTreatmentConsiderations/OtherMyoclonusPharmacologicValproic acidFirst drug of choice; diminishes myoclonus & frequency of generalized seizuresClonazepamFDA-approved for treatment of myoclonic seizures; used as add-on therapy 1High-dose piracetamUseful in treatment of myoclonus 2Levetiracetam, brivaracetam, 3 perampanel 4Appears effective for both myoclonus & generalized seizuresTopiramate & zonisamideMay be used as add-on therapiesN-acetylcysteineVari | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. t drug of choice; diminishes myoclonus & frequency of generalized seizuresClonazepamFDA-approved for treatment of myoclonic seizures; used as add-on therapy 1High-dose piracetamUseful in treatment of myoclonus 2Levetiracetam, brivaracetam, 3 perampanel 4Appears effective for both myoclonus & generalized seizuresTopiramate & zonisamideMay be used as add-on therapiesN-acetylcysteineVariable results 5Vagus nerve stimulationReduces seizures & significantly improves cerebellar function on neurologic exam 6OtherAvoid extreme stimuli (lights, noises, stress).SeizuresAntiseizure medicationActivities of daily livingPT/OTPT (balance exercises, gait training, muscle strengthening) to maintain mobility & function 1OT to optimize ADL (incl use of adaptive devices, e.g., weighted eating utensils & | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. add-on therapiesN-acetylcysteineVariable results 5Vagus nerve stimulationReduces seizures & significantly improves cerebellar function on neurologic exam 6OtherAvoid extreme stimuli (lights, noises, stress).SeizuresAntiseizure medicationActivities of daily livingPT/OTPT (balance exercises, gait training, muscle strengthening) to maintain mobility & function 1OT to optimize ADL (incl use of adaptive devices, e.g., weighted eating utensils & dressing hooks)Consider adaptive devices to maintain/improve independence in mobility (e.g., canes, walkers, motorized chairs).Home adaptations to prevent falls (e.g., grab bars, raised toilet seats) & improve mobility (e.g., ramps to accommodate motorized chairs)Developmental delay / Intellectual disabilitySee Developmental Delay / Intellectual Disability Management Issues.Dys | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. ., weighted eating utensils & dressing hooks)Consider adaptive devices to maintain/improve independence in mobility (e.g., canes, walkers, motorized chairs).Home adaptations to prevent falls (e.g., grab bars, raised toilet seats) & improve mobility (e.g., ramps to accommodate motorized chairs)Developmental delay / Intellectual disabilitySee Developmental Delay / Intellectual Disability Management Issues.DysarthriaSpeech & language therapyConsider alternative communication methods as needed (e.g., writing pads & digital devices).DysphagiaFeeding therapy programs to improve nutrition & dysphagia & reduce aspiration riskVideo esophagram may help define best food consistency.Education re strategies to mitigate aspirationPEG tube in advanced casesWeightNutrition assessmentConsider nutritional & vitamin supplementation to meet | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. Developmental Delay / Intellectual Disability Management Issues.DysarthriaSpeech & language therapyConsider alternative communication methods as needed (e.g., writing pads & digital devices).DysphagiaFeeding therapy programs to improve nutrition & dysphagia & reduce aspiration riskVideo esophagram may help define best food consistency.Education re strategies to mitigate aspirationPEG tube in advanced casesWeightNutrition assessmentConsider nutritional & vitamin supplementation to meet dietary needsAvoid obesity, which can exacerbate difficulties w/ambulation & mobilityFamily support/resourcesPsychotherapy, peer supportADL = activities of daily living; OT = occupational therapy; PEG = percutaneous endoscopic gastrostomy; PT = physical therapy1. Shahwan et al 2. Koskiniemi et al 3. Kälviäinen et al 4. Crespel et al 5. Edwards et al 6. Smith | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. r nutritional & vitamin supplementation to meet dietary needsAvoid obesity, which can exacerbate difficulties w/ambulation & mobilityFamily support/resourcesPsychotherapy, peer supportADL = activities of daily living; OT = occupational therapy; PEG = percutaneous endoscopic gastrostomy; PT = physical therapy1. Shahwan et al 2. Koskiniemi et al 3. Kälviäinen et al 4. Crespel et al 5. Edwards et al 6. Smith et al Developmental Delay / Intellectual Disability Management IssuesThe following information represents typical management recommendations for school-age individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider:Individualized education plan (IEP) services | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. 5. Edwards et al 6. Smith et al Developmental Delay / Intellectual Disability Management IssuesThe following information represents typical management recommendations for school-age individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life. Some issues to consider:Individualized education plan (IEP) services:An IEP provides specially designed instruction and related services to children who qualify.IEP services will be reviewed annually to determine whether any changes are needed.As required by special education law, children should be in the least restrictive environment feasible at school and included in general education as much as possible and when appropriate.PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. :Individualized education plan (IEP) services:An IEP provides specially designed instruction and related services to children who qualify.IEP services will be reviewed annually to determine whether any changes are needed.As required by special education law, children should be in the least restrictive environment feasible at school and included in general education as much as possible and when appropriate.PT, OT, and speech services will be provided in the IEP to the extent that the need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21.A 504 plan (Section 504: a US federal statute that | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. need affects the child's access to academic material. Beyond that, private supportive therapies based on the affected individual's needs may be considered. Specific recommendations regarding type of therapy can be made by a developmental pediatrician.As a child enters the teen years, a transition plan should be discussed and incorporated in the IEP. For those receiving IEP services, the public school district is required to provide services until age 21.A 504 plan (Section 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text.Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. 504: a US federal statute that prohibits discrimination based on disability) can be considered for those who require accommodations or modifications such as front-of-class seating, assistive technology devices, classroom scribes, extra time between classes, modified assignments, and enlarged text.Developmental Disabilities Administration (DDA) enrollment is recommended. DDA is a US public agency that provides services and support to qualified individuals. Eligibility differs by state but is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.SurveillanceTable 5. Recommended Surveillance for Individuals with EPM1View in own windowSystem/ConcernEvaluationFrequencyMyoclonusSeverity of myoclonus using UMRSAt least annuallySeizuresSeizure type & frequencyCerebellar involvementClinical evalPer symptom progressionDysa | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. is typically determined by diagnosis and/or associated cognitive/adaptive disabilities.Families with limited income and resources may also qualify for supplemental security income (SSI) for their child with a disability.SurveillanceTable 5. Recommended Surveillance for Individuals with EPM1View in own windowSystem/ConcernEvaluationFrequencyMyoclonusSeverity of myoclonus using UMRSAt least annuallySeizuresSeizure type & frequencyCerebellar involvementClinical evalPer symptom progressionDysarthriaNeed for alternative communication method or speech therapyDysphagiaAssess aspiration risk & feeding methodsWeight / Nutritional statusMonitor BMI.Consult a nutritionist.High-calorie supplementationActivities of daily livingClinically to evaluate rehabilitation planAt least annuallySchool performanceInterviewCognitive /PsychiatricEvaluate mood, signs of psychosis, & cognitive complaints to identify need for pharmacologic & psychotherapeutic interventions | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. Clinical evalPer symptom progressionDysarthriaNeed for alternative communication method or speech therapyDysphagiaAssess aspiration risk & feeding methodsWeight / Nutritional statusMonitor BMI.Consult a nutritionist.High-calorie supplementationActivities of daily livingClinically to evaluate rehabilitation planAt least annuallySchool performanceInterviewCognitive /PsychiatricEvaluate mood, signs of psychosis, & cognitive complaints to identify need for pharmacologic & psychotherapeutic interventions.Per symptom progression & development of psychiatric symptomsFamily support/resourcesInterviewAnnuallyBMI = body mass index; UMRS = Unified Myoclonus Rating ScaleAgents/Circumstances to AvoidPhenytoin should be avoided, as it has been found to have aggravating side effects on the associated neurologic symptoms, and may even accelerate cerebellar degeneration .Sodium channel blockers (carbamazepine, oxcarbazepine, phenytoin) and GABAergic drugs (tiagabine | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. for pharmacologic & psychotherapeutic interventions.Per symptom progression & development of psychiatric symptomsFamily support/resourcesInterviewAnnuallyBMI = body mass index; UMRS = Unified Myoclonus Rating ScaleAgents/Circumstances to AvoidPhenytoin should be avoided, as it has been found to have aggravating side effects on the associated neurologic symptoms, and may even accelerate cerebellar degeneration .Sodium channel blockers (carbamazepine, oxcarbazepine, phenytoin) and GABAergic drugs (tiagabine, vigabatrin) as well as gabapentin and pregabalin should in general be avoided as they may aggravate myoclonus and myoclonic seizures .Evaluation of Relatives at RiskSee Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.Therapies Under InvestigationSearch ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1142/ | V9L3B1X | Progressive Myoclonic Epilepsy Type 1 | C0751785 | 4 | progressive myoclonic epilepsy type 1. ) and GABAergic drugs (tiagabine, vigabatrin) as well as gabapentin and pregabalin should in general be avoided as they may aggravate myoclonus and myoclonic seizures .Evaluation of Relatives at RiskSee Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.Therapies Under InvestigationSearch ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder. | [
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medlineplus | https://medlineplus.gov/genetics/condition/pallister-hall-syndrome/ | 05KYlXB | Pallister-Hall syndrome | C0265220 | 5 | pallister-hall syndrome. Pallister-Hall syndrome is a disorder that affects the development of many parts of the body. Most people with this condition have extra fingers and/or toes (polydactyly), and the skin between some fingers or toes may be fused (cutaneous syndactyly). An abnormal growth in the brain called a hypothalamic hamartoma is characteristic of this disorder. In many cases, these growths do not cause any health problems; however, some hypothalamic hamartomas lead to seizures or hormone abnormalities that can be life-threatening in infancy. Other features of Pallister-Hall syndrome include a malformation of the airway called a bifid epiglottis, an obstruction of the anal opening (imperforate anus), and kidney abnormalities. Although the signs and symptoms of this disorder vary from mild to severe, only a small percentage of affected people have serious complications.FrequencyThis condition is very rare; its prevalence is unknown.CausesMutations in the GLI | [
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medlineplus | https://medlineplus.gov/genetics/condition/pallister-hall-syndrome/ | 05KYlXB | Pallister-Hall syndrome | C0265220 | 5 | pallister-hall syndrome. hamartomas lead to seizures or hormone abnormalities that can be life-threatening in infancy. Other features of Pallister-Hall syndrome include a malformation of the airway called a bifid epiglottis, an obstruction of the anal opening (imperforate anus), and kidney abnormalities. Although the signs and symptoms of this disorder vary from mild to severe, only a small percentage of affected people have serious complications.FrequencyThis condition is very rare; its prevalence is unknown.CausesMutations in the GLI3 gene cause Pallister-Hall syndrome. This gene provides instructions for making a protein that controls gene expression, which is a process that regulates whether genes are turned on or off in particular cells. By interacting with certain genes at specific times during development, the GLI3 protein plays a role in the normal shaping (patterning) of many organs and tissues before birth.Mutations that cause Pallister-Hall syndrome typically lead to the production of an abnormally short | [
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medlineplus | https://medlineplus.gov/genetics/condition/pallister-hall-syndrome/ | 05KYlXB | Pallister-Hall syndrome | C0265220 | 5 | pallister-hall syndrome. is unknown.CausesMutations in the GLI3 gene cause Pallister-Hall syndrome. This gene provides instructions for making a protein that controls gene expression, which is a process that regulates whether genes are turned on or off in particular cells. By interacting with certain genes at specific times during development, the GLI3 protein plays a role in the normal shaping (patterning) of many organs and tissues before birth.Mutations that cause Pallister-Hall syndrome typically lead to the production of an abnormally short version of the GLI3 protein. Unlike the normal GLI3 protein, which can turn target genes on or off, the short protein can only turn off (repress) target genes. Researchers are working to determine how this change in the protein's function affects early development. It is uncertain how GLI3 mutations can cause polydactyly, hypothalamic hamartoma, and the other features of Pallister-Hall syndrome.Learn more about the gene associated with Pallist | [
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medlineplus | https://medlineplus.gov/genetics/condition/pallister-hall-syndrome/ | 05KYlXB | Pallister-Hall syndrome | C0265220 | 5 | pallister-hall syndrome. typically lead to the production of an abnormally short version of the GLI3 protein. Unlike the normal GLI3 protein, which can turn target genes on or off, the short protein can only turn off (repress) target genes. Researchers are working to determine how this change in the protein's function affects early development. It is uncertain how GLI3 mutations can cause polydactyly, hypothalamic hamartoma, and the other features of Pallister-Hall syndrome.Learn more about the gene associated with Pallister-Hall syndrome
GLI3
Inheritance PatternThis condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits a mutation in the GLI3 gene from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family. | [
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medlineplus | https://medlineplus.gov/genetics/condition/pallister-hall-syndrome/ | 05KYlXB | Pallister-Hall syndrome | C0265220 | 5 | pallister-hall syndrome. Learn more about the gene associated with Pallister-Hall syndrome
GLI3
Inheritance PatternThis condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits a mutation in the GLI3 gene from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family. | [
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orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=431361 | joB2RR6 | Progressive encephalopathy with leukodystrophy due to DECR deficiency | C1857252 | 6 | progressive encephalopathy with leukodystrophy due to decr deficiency. Progressive encephalopathy with leukodystrophy due to DECR deficiency is a rare mitochondrial disease, which presents with neonatal hypotonia, central nervous system abnormalities (ventriculomegaly, corpus callosum hypoplasia, cerebellar atrophy), acquired microcephaly, failure to thrive, developmental delay and intermittent lactic acidosis provoked by catabolic stress (e.g. infection). Hyperlysinemia and elevated C10:2 carnitine can be detected in plasma. Later on, epilepsy, cerebellar ataxia, renal tubular acidosis, severe encephalopathy, dystonia, spastic quadriplegia and other complications may develop. | [
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wikipedia | https://en.wikipedia.org/wiki/2,4_Dienoyl-CoA_reductase_deficiency | jPnzDzW | 2,4 Dienoyl-CoA reductase deficiency | C1857252 | 7 | 2,4 dienoyl-coa reductase deficiency. 2,4 Dienoyl-CoA reductase deficiencyOther namesDECRD
2,4 Dienoyl-CoA reductase deficiency is an inborn error of metabolism resulting in defective fatty acid oxidation caused by a deficiency of the enzyme 2,4 Dienoyl-CoA reductase. Lysine degradation is also affected in this disorder leading to hyperlysinemia. The disorder is inherited in an autosomal recessive manner, meaning an individual must inherit mutations in NADK2, located at 5p13.2 from both of their parents. NADK2 encodes the mitochondrial NAD kinase. A defect in this enzyme leads to deficient mitochondrial nicotinamide adenine dinucleotide phosphate levels. 2,4 Dienoyl-CoA reductase, but also lysine degradation are performed by NADP-dependent oxidoreductases explaining how NADK2 deficiency can lead to multiple enzyme defects.
2,4-Dienoyl-CoA reductase deficiency was initially described in 1990 based on a single case of a black female who presented | [
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wikipedia | https://en.wikipedia.org/wiki/2,4_Dienoyl-CoA_reductase_deficiency | jPnzDzW | 2,4 Dienoyl-CoA reductase deficiency | C1857252 | 7 | 2,4 dienoyl-coa reductase deficiency. in NADK2, located at 5p13.2 from both of their parents. NADK2 encodes the mitochondrial NAD kinase. A defect in this enzyme leads to deficient mitochondrial nicotinamide adenine dinucleotide phosphate levels. 2,4 Dienoyl-CoA reductase, but also lysine degradation are performed by NADP-dependent oxidoreductases explaining how NADK2 deficiency can lead to multiple enzyme defects.
2,4-Dienoyl-CoA reductase deficiency was initially described in 1990 based on a single case of a black female who presented with persistent hypotonia. Laboratory investigations revealed elevated lysine, low levels of carnitine and an abnormal acylcarnitine profile in urine and blood. The abnormal acylcarnitine species was eventually identified as 2-trans,4-cis-decadienoylcarnitine, an intermediate of linoleic acid metabolism. The index case died of respiratory failure at four months of age. Postmortem enzyme analysis on liver and muscle samples revealed decreased 2,4-die | [
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wikipedia | https://en.wikipedia.org/wiki/2,4_Dienoyl-CoA_reductase_deficiency | jPnzDzW | 2,4 Dienoyl-CoA reductase deficiency | C1857252 | 7 | 2,4 dienoyl-coa reductase deficiency. in 1990 based on a single case of a black female who presented with persistent hypotonia. Laboratory investigations revealed elevated lysine, low levels of carnitine and an abnormal acylcarnitine profile in urine and blood. The abnormal acylcarnitine species was eventually identified as 2-trans,4-cis-decadienoylcarnitine, an intermediate of linoleic acid metabolism. The index case died of respiratory failure at four months of age. Postmortem enzyme analysis on liver and muscle samples revealed decreased 2,4-dienoyl-CoA reductase activity when compared to normal controls. A second case with failure to thrive, developmental delay, lactic acidosis and severe encephalopathy was reported in 2014.
2,4-Dienoyl-CoA reductase deficiency was included as a secondary condition in the American College of Medical Genetics Recommended Uniform Panel for newborn screening. Its status as a secondary condition means there was not enough evidence of benefit to include it as a primary target, | [
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wikipedia | https://en.wikipedia.org/wiki/2,4_Dienoyl-CoA_reductase_deficiency | jPnzDzW | 2,4 Dienoyl-CoA reductase deficiency | C1857252 | 7 | 2,4 dienoyl-coa reductase deficiency. analysis on liver and muscle samples revealed decreased 2,4-dienoyl-CoA reductase activity when compared to normal controls. A second case with failure to thrive, developmental delay, lactic acidosis and severe encephalopathy was reported in 2014.
2,4-Dienoyl-CoA reductase deficiency was included as a secondary condition in the American College of Medical Genetics Recommended Uniform Panel for newborn screening. Its status as a secondary condition means there was not enough evidence of benefit to include it as a primary target, but it may be detected during the screening process or as part of a differential diagnosis when detecting conditions included as primary target. Despite its inclusion in newborn screening programs in several states for a number of years, no cases have been identified via neonatal screening.
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wikipedia | https://en.wikipedia.org/wiki/2,4_Dienoyl-CoA_reductase_deficiency | jPnzDzW | 2,4 Dienoyl-CoA reductase deficiency | C1857252 | 7 | 2,4 dienoyl-coa reductase deficiency. not enough evidence of benefit to include it as a primary target, but it may be detected during the screening process or as part of a differential diagnosis when detecting conditions included as primary target. Despite its inclusion in newborn screening programs in several states for a number of years, no cases have been identified via neonatal screening.
References
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wikipedia | https://en.wikipedia.org/wiki/2,4_Dienoyl-CoA_reductase_deficiency | jPnzDzW | 2,4 Dienoyl-CoA reductase deficiency | C1857252 | 7 | 2,4 dienoyl-coa reductase deficiency. output code.cs1-code{color:inherit;background:inherit;border:none;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{font-size:100%}.mw-parser-output .cs1-maint{display:none;color:#33aa33;margin-left:0.3em}.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern | [
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wikipedia | https://en.wikipedia.org/wiki/2,4_Dienoyl-CoA_reductase_deficiency | jPnzDzW | 2,4 Dienoyl-CoA reductase deficiency | C1857252 | 7 | 2,4 dienoyl-coa reductase deficiency. 1-maint{display:none;color:#33aa33;margin-left:0.3em}.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}"222745 2,4-DIENOYL-CoA REDUCTASE 1; DECR1". Johns Hopkins University. Retrieved 2013-12-01.
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wikipedia | https://en.wikipedia.org/wiki/2,4_Dienoyl-CoA_reductase_deficiency | jPnzDzW | 2,4 Dienoyl-CoA reductase deficiency | C1857252 | 7 | 2,4 dienoyl-coa reductase deficiency. }.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}"222745 2,4-DIENOYL-CoA REDUCTASE 1; DECR1". Johns Hopkins University. Retrieved 2013-12-01.
^ a b Sander, Houten; Denis, Simone; te Brinke, Heleen; Jongejan, Aldo; van Kampen, Antoine H.C.; Bradley, Edward J.; Baas, Frank; Hennekam, Raoul C.M.; Millington, David S.; Young, Sarah P.; | [
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wikipedia | https://en.wikipedia.org/wiki/2,4_Dienoyl-CoA_reductase_deficiency | jPnzDzW | 2,4 Dienoyl-CoA reductase deficiency | C1857252 | 7 | 2,4 dienoyl-coa reductase deficiency. Johns Hopkins University. Retrieved 2013-12-01.
^ a b Sander, Houten; Denis, Simone; te Brinke, Heleen; Jongejan, Aldo; van Kampen, Antoine H.C.; Bradley, Edward J.; Baas, Frank; Hennekam, Raoul C.M.; Millington, David S.; Young, Sarah P.; Frazier, Dianne M.; Gucsavas-Calikoglu, Muge; Wanders, Ronald J.A. (2014). "Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia". Human Molecular Genetics. 23 (18): 5009–5016. doi:10.109 | [
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wikipedia | https://en.wikipedia.org/wiki/2,4_Dienoyl-CoA_reductase_deficiency | jPnzDzW | 2,4 Dienoyl-CoA reductase deficiency | C1857252 | 7 | 2,4 dienoyl-coa reductase deficiency. , David S.; Young, Sarah P.; Frazier, Dianne M.; Gucsavas-Calikoglu, Muge; Wanders, Ronald J.A. (2014). "Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia". Human Molecular Genetics. 23 (18): 5009–5016. doi:10.1093/hmg/ddu218. PMID 24847004.
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wikipedia | https://en.wikipedia.org/wiki/2,4_Dienoyl-CoA_reductase_deficiency | jPnzDzW | 2,4 Dienoyl-CoA reductase deficiency | C1857252 | 7 | 2,4 dienoyl-coa reductase deficiency. ): 5009–5016. doi:10.1093/hmg/ddu218. PMID 24847004.
^ Morris, Andrew A.M.; Spiekerkoetter, Ute (2012). "Disorders of Mitochondrial Fatty Acid Oxidation and Related Metabolic Pathways". In Saudubray, Jean-Marie; van den Berghe, Georges; Walter, John H. (eds.). Inborn Metabolic Diseases: Diagnosis and Treatment (5th ed.). New York: Springer. pp. 201–216. ISBN 978-3-642-15719-6.
^ Watson, M. S.; Mann, M. Y.; Lloyd-Puryear, M. A.; Rinaldo, P.; Howell, R. R. (2006). | [
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wikipedia | https://en.wikipedia.org/wiki/2,4_Dienoyl-CoA_reductase_deficiency | jPnzDzW | 2,4 Dienoyl-CoA reductase deficiency | C1857252 | 7 | 2,4 dienoyl-coa reductase deficiency. ter, John H. (eds.). Inborn Metabolic Diseases: Diagnosis and Treatment (5th ed.). New York: Springer. pp. 201–216. ISBN 978-3-642-15719-6.
^ Watson, M. S.; Mann, M. Y.; Lloyd-Puryear, M. A.; Rinaldo, P.; Howell, R. R. (2006). "Executive Summary". Genetics in Medicine. 8 (Suppl 1): 1S–252S. doi:10.1097/01.gim.0000223891.82390.ad. PMC 3111605. PMID 16783161.
^ American College of Medical Genetics Newborn Screening Expert Group (2006). "Newborn screening: Toward a uniform screening panel and system--executive summary" | [
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wikipedia | https://en.wikipedia.org/wiki/2,4_Dienoyl-CoA_reductase_deficiency | jPnzDzW | 2,4 Dienoyl-CoA reductase deficiency | C1857252 | 7 | 2,4 dienoyl-coa reductase deficiency. .; Howell, R. R. (2006). "Executive Summary". Genetics in Medicine. 8 (Suppl 1): 1S–252S. doi:10.1097/01.gim.0000223891.82390.ad. PMC 3111605. PMID 16783161.
^ American College of Medical Genetics Newborn Screening Expert Group (2006). "Newborn screening: Toward a uniform screening panel and system--executive summary". Pediatrics. 117 (5 Pt 2): S296–S307. doi:10.1542/peds.2005-2633I. PMID 16735256.
^ "2,4-Dienoyl-CoA Reductase Deficiency". Baby's First Test. Retrieved 2013-12-30.
External links
ClassificationDOMIM: 222745MeSH: C565624
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wikipedia | https://en.wikipedia.org/wiki/2,4_Dienoyl-CoA_reductase_deficiency | jPnzDzW | 2,4 Dienoyl-CoA reductase deficiency | C1857252 | 7 | 2,4 dienoyl-coa reductase deficiency. : Toward a uniform screening panel and system--executive summary". Pediatrics. 117 (5 Pt 2): S296–S307. doi:10.1542/peds.2005-2633I. PMID 16735256.
^ "2,4-Dienoyl-CoA Reductase Deficiency". Baby's First Test. Retrieved 2013-12-30.
External links
ClassificationDOMIM: 222745MeSH: C565624
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wikipedia | https://en.wikipedia.org/wiki/2,4_Dienoyl-CoA_reductase_deficiency | jPnzDzW | 2,4 Dienoyl-CoA reductase deficiency | C1857252 | 7 | 2,4 dienoyl-coa reductase deficiency. 222745MeSH: C565624
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wikipedia | https://en.wikipedia.org/wiki/2,4_Dienoyl-CoA_reductase_deficiency | jPnzDzW | 2,4 Dienoyl-CoA reductase deficiency | C1857252 | 7 | 2,4 dienoyl-coa reductase deficiency. font-size:114%;margin:0 4em}.mw-parser-output .infobox .navbar{font-size:100%}.mw-parser-output .navbox .navbar{display:block;font-size:100%}.mw-parser-output .navbox-title .navbar{float:left;text-align:left;margin-right:0.5em}vteInborn error of lipid metabolism: fatty-acid metabolism disordersSynthesis
Biotinidase deficiency (BTD)
DegradationAcyltransport
Carnitine
CPT1
CPT2
CDSP
CACTD
Adrenoleukodystrophy (ALD)
BetaoxidationGeneral
Acyl CoA dehydrogenase
Short-chain SCADD
Medium-chain MCADD
Long-chain 3-hydroxy LCHAD
Very long-chain VLCADD
Mitochondrial trifunctional protein deficiency (MTPD): Acute fatty liver | [
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wikipedia | https://en.wikipedia.org/wiki/2,4_Dienoyl-CoA_reductase_deficiency | jPnzDzW | 2,4 Dienoyl-CoA reductase deficiency | C1857252 | 7 | 2,4 dienoyl-coa reductase deficiency. left;margin-right:0.5em}vteInborn error of lipid metabolism: fatty-acid metabolism disordersSynthesis
Biotinidase deficiency (BTD)
DegradationAcyltransport
Carnitine
CPT1
CPT2
CDSP
CACTD
Adrenoleukodystrophy (ALD)
BetaoxidationGeneral
Acyl CoA dehydrogenase
Short-chain SCADD
Medium-chain MCADD
Long-chain 3-hydroxy LCHAD
Very long-chain VLCADD
Mitochondrial trifunctional protein deficiency (MTPD): Acute fatty liver of pregnancy
Unsaturated
2,4 Dienoyl-CoA reductase deficiency (DECRD)
Odd chain
Propionic acidemia (PCC deficiency)
Other
3-hydroxyacyl-coenzyme A dehydrogenase deficiency (HADHD)
Glutaric acidemia type 2 (MADD)
Toacetyl-CoA
Malonic aciduria (MCD)
Aldehyde
Sjögren–Larsson syndrome (SLS)
<!--
NewPP limit report
Parsed by mw1373
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wikipedia | https://en.wikipedia.org/wiki/2,4_Dienoyl-CoA_reductase_deficiency | jPnzDzW | 2,4 Dienoyl-CoA reductase deficiency | C1857252 | 7 | 2,4 dienoyl-coa reductase deficiency. Mitochondrial trifunctional protein deficiency (MTPD): Acute fatty liver of pregnancy
Unsaturated
2,4 Dienoyl-CoA reductase deficiency (DECRD)
Odd chain
Propionic acidemia (PCC deficiency)
Other
3-hydroxyacyl-coenzyme A dehydrogenase deficiency (HADHD)
Glutaric acidemia type 2 (MADD)
Toacetyl-CoA
Malonic aciduria (MCD)
Aldehyde
Sjögren–Larsson syndrome (SLS)
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Cached time: 20210110224510
Cache expiry: 2592000
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Real time usage: 0.384 seconds
Preprocessor visited node count: 1127/1000000
Post‐expand include size: 44440/2097152 bytes
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wikipedia | https://en.wikipedia.org/wiki/2,4_Dienoyl-CoA_reductase_deficiency | jPnzDzW | 2,4 Dienoyl-CoA reductase deficiency | C1857252 | 7 | 2,4 dienoyl-coa reductase deficiency. -
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wikipedia | https://en.wikipedia.org/wiki/2,4_Dienoyl-CoA_reductase_deficiency | jPnzDzW | 2,4 Dienoyl-CoA reductase deficiency | C1857252 | 7 | 2,4 dienoyl-coa reductase deficiency. 52 bytes
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wikipedia | https://en.wikipedia.org/wiki/2,4_Dienoyl-CoA_reductase_deficiency | jPnzDzW | 2,4 Dienoyl-CoA reductase deficiency | C1857252 | 7 | 2,4 dienoyl-coa reductase deficiency. >
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wikipedia | https://en.wikipedia.org/wiki/2,4_Dienoyl-CoA_reductase_deficiency | jPnzDzW | 2,4 Dienoyl-CoA reductase deficiency | C1857252 | 7 | 2,4 dienoyl-coa reductase deficiency. e_web
14.97% 52.972 1 Template:Medical_resources
13.44% 47.559 3 Template:Navbox
11.33% 40.112 1 Template:Fatty-acid_metabolism_disorders
8.63% 30.548 2 Template:Hlist
8.43% 29.832 3 Template:Cite_journal
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gard | https://rarediseases.info.nih.gov/diseases/1855/dicarboxylic-aminoaciduria | JnElMZm | Dicarboxylic aminoaciduria | C1857253 | 8 | dicarboxylic aminoaciduria. Dicarboxylic aminoaciduria is a rare metabolic disorder characterized by the excessive loss of aspartate and glutamate in urine. Symptoms have varied greatly among the few reported cases. Dicarboxylic aminoaciduria is caused by mutations in the SLC1A1 gene. It is inherited in an autosomal recessive fashion. | [
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orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2195 | wo7m8p6 | Dicarboxylic aminoaciduria | C1857253 | 9 | dicarboxylic aminoaciduria. Dicarboxylicaminoaciduria is characterised by infantile-onset hypoglycaemia and hyperprolinaemia associated, in certain cases, with intellectual deficit.
Epidemiology
Less than 10 cases have been reported to date.
Etiology
Defects in renal and intestinal glutamate and aspartate transport were also reported, suggesting that anomalies of the EAAC1 transporter, involved in the transport of these two amino acids, are the underlying cause of this syndrome. | [
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wikipedia | https://en.wikipedia.org/wiki/Diastrophic_dysplasia | YJWxNNZ | Diastrophic dysplasia | C1857255 | 10 | diastrophic dysplasia. This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.Find sources: "Diastrophic dysplasia" – news · newspapers · books · scholar · JSTOR (July 2008) (Learn how and when to remove this template message)
Diastrophic dysplasiaOther namesDTDSpecialtyMedical genetics
Diastrophic dysplasia is an autosomal recessive dysplasia which affects cartilage and bone development. ("Diastrophism" is a general word referring to a twisting.) Diastrophic dysplasia is due to mutations in the SLC26A2 gene.
Affected individuals have short stature with very short arms and legs and joint problems that restrict mobility.
Contents
1 Signs and symptoms
2 Genetic
3 Prevalence
4 See also
5 References
6 External links
Signs and symptoms
This condition is also characterized by an unusual clubfoot with twisting of the metatarsals, inward- and upward-turning foot, tarsus varus and | [
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wikipedia | https://en.wikipedia.org/wiki/Diastrophic_dysplasia | YJWxNNZ | Diastrophic dysplasia | C1857255 | 10 | diastrophic dysplasia. . ("Diastrophism" is a general word referring to a twisting.) Diastrophic dysplasia is due to mutations in the SLC26A2 gene.
Affected individuals have short stature with very short arms and legs and joint problems that restrict mobility.
Contents
1 Signs and symptoms
2 Genetic
3 Prevalence
4 See also
5 References
6 External links
Signs and symptoms
This condition is also characterized by an unusual clubfoot with twisting of the metatarsals, inward- and upward-turning foot, tarsus varus and inversion adducted appearances. Furthermore, they classically present with scoliosis (progressive curvature of the spine) and unusually positioned thumbs (hitchhiker thumbs). About half of infants with diastrophic dysplasia are born with an opening in the roof of the mouth called a cleft palate. Swelling of the external ears is also common in newborns and can lead to thickened, deformed ears.
The signs and symptoms of diastrophic dysplasia are similar to those of another skeletal disorder called ate | [
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wikipedia | https://en.wikipedia.org/wiki/Diastrophic_dysplasia | YJWxNNZ | Diastrophic dysplasia | C1857255 | 10 | diastrophic dysplasia. foot, tarsus varus and inversion adducted appearances. Furthermore, they classically present with scoliosis (progressive curvature of the spine) and unusually positioned thumbs (hitchhiker thumbs). About half of infants with diastrophic dysplasia are born with an opening in the roof of the mouth called a cleft palate. Swelling of the external ears is also common in newborns and can lead to thickened, deformed ears.
The signs and symptoms of diastrophic dysplasia are similar to those of another skeletal disorder called atelosteogenesis, type 2; however diastrophic dysplasia tends to be less severe.
Genetic
Diastrophic dysplasia has an autosomal recessive pattern of inheritance.
It is one of a spectrum of skeletal disorders caused by mutations in the SLC26A2 gene. The protein encoded by this gene is essential for the normal development of cartilage and for its conversion to bone. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to | [
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wikipedia | https://en.wikipedia.org/wiki/Diastrophic_dysplasia | YJWxNNZ | Diastrophic dysplasia | C1857255 | 10 | diastrophic dysplasia. of another skeletal disorder called atelosteogenesis, type 2; however diastrophic dysplasia tends to be less severe.
Genetic
Diastrophic dysplasia has an autosomal recessive pattern of inheritance.
It is one of a spectrum of skeletal disorders caused by mutations in the SLC26A2 gene. The protein encoded by this gene is essential for the normal development of cartilage and for its conversion to bone. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, but in adulthood this tissue continues to cover and protect the ends of bones and is present in the nose and external ears. Mutations in the SLC26A2 gene alter the structure of developing cartilage, preventing bones from forming properly and resulting in the skeletal problems characteristic of diastrophic dysplasia.
This condition is an autosomal recessive disorder, meaning that the defective gene is located on an autosome, and both parents must carry one copy of the defective gene in order to have a | [
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wikipedia | https://en.wikipedia.org/wiki/Diastrophic_dysplasia | YJWxNNZ | Diastrophic dysplasia | C1857255 | 10 | diastrophic dysplasia. Most cartilage is later converted to bone, but in adulthood this tissue continues to cover and protect the ends of bones and is present in the nose and external ears. Mutations in the SLC26A2 gene alter the structure of developing cartilage, preventing bones from forming properly and resulting in the skeletal problems characteristic of diastrophic dysplasia.
This condition is an autosomal recessive disorder, meaning that the defective gene is located on an autosome, and both parents must carry one copy of the defective gene in order to have a child born with the disorder. The parents of a child with an autosomal recessive disorder are usually not affected by the disorder.
Prevalence
Diastrophic dysplasia affects about one in 100,000 births.
See also
Achondrogenesis type 1B
References
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wikipedia | https://en.wikipedia.org/wiki/Diastrophic_dysplasia | YJWxNNZ | Diastrophic dysplasia | C1857255 | 10 | diastrophic dysplasia. gene in order to have a child born with the disorder. The parents of a child with an autosomal recessive disorder are usually not affected by the disorder.
Prevalence
Diastrophic dysplasia affects about one in 100,000 births.
See also
Achondrogenesis type 1B
References
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wikipedia | https://en.wikipedia.org/wiki/Diastrophic_dysplasia | YJWxNNZ | Diastrophic dysplasia | C1857255 | 10 | diastrophic dysplasia. -visible-error{font-size:100%}.mw-parser-output .cs1-maint{display:none;color:#33aa33;margin-left:0.3em}.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}Hästbacka J, Sistonen P, Kaitila I, Weiff | [
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wikipedia | https://en.wikipedia.org/wiki/Diastrophic_dysplasia | YJWxNNZ | Diastrophic dysplasia | C1857255 | 10 | diastrophic dysplasia. kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}Hästbacka J, Sistonen P, Kaitila I, Weiffenbach B, Kidd KK, De La Chapelle A (December 1991). "A linkage map spanning the locus for diastrophic dysplasia (DTD)". Genomics. 11 (4): 968–973. doi:10.1016/0888-7543(91)90021-6. PMID 1783404.
^ "diastrophic - Definition from the Merriam-Webster Online Dictionary | [
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