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omim | https://www.omim.org/entry/252270 | YNNWRxG | MONOSOMY 7 OF BONE MARROW | C1854978 | 31,748 | monosomy 7 of bone marrow. A number sign (#) is used with this entry because loss of chromosome 7 or deletion of genes on chromosome 7q are associated with development of myelodysplastic syndrome and acute myelogenous leukemia (AML). One putative candidate gene in this region is EZH2 (601573).
Description
Monosomy 7 or partial deletion of the long arm of chromosome 7 (7q-) is a frequent cytogenetic finding in the bone marrow of patients with myelodysplasia (MDS) and acute myelogenous leukemia (AML). Furthermore, monosomy 7 or 7q- is the most frequent abnormality of karyotype in cases of AML that occur after cytotoxic cancer therapy or occupational exposure to mutagens. The age distribution of de novo cases shows peaks in the first and fifth decades. Monosomy 7 is found in about 5% of de novo and 40% of secondary cases of AML. These findings suggest that loss of certain genes at this region is an important event in the development of myelodysplasia ( | [
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omim | https://www.omim.org/entry/252270 | YNNWRxG | MONOSOMY 7 OF BONE MARROW | C1854978 | 31,748 | monosomy 7 of bone marrow. and acute myelogenous leukemia (AML). Furthermore, monosomy 7 or 7q- is the most frequent abnormality of karyotype in cases of AML that occur after cytotoxic cancer therapy or occupational exposure to mutagens. The age distribution of de novo cases shows peaks in the first and fifth decades. Monosomy 7 is found in about 5% of de novo and 40% of secondary cases of AML. These findings suggest that loss of certain genes at this region is an important event in the development of myelodysplasia (summary by Shannon et al., 1989).
Clinical Features
Childhood bone marrow monosomy 7 has been observed in 2 or more sibs at least 7 times, according to Shannon et al. (1989). The segment that is deleted in common in these cases is 7q22-q34. Shannon et al. (1989) studied 3 families, each with 2 cases with bone marrow monosomy 7. The first family | [
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] |
omim | https://www.omim.org/entry/252270 | YNNWRxG | MONOSOMY 7 OF BONE MARROW | C1854978 | 31,748 | monosomy 7 of bone marrow. important event in the development of myelodysplasia (summary by Shannon et al., 1989).
Clinical Features
Childhood bone marrow monosomy 7 has been observed in 2 or more sibs at least 7 times, according to Shannon et al. (1989). The segment that is deleted in common in these cases is 7q22-q34. Shannon et al. (1989) studied 3 families, each with 2 cases with bone marrow monosomy 7. The first family was ascertained through a 6-year-old girl with AML and bone marrow monosomy 7. Her 5-year-old brother, who shared HLA antigens, was found during evaluation for donation of bone marrow to have mild thrombocytopenia, erythrocyte macrocytosis, and a minor subpopulation of bone marrow cells with monosomy 7. He went on to develop AML. The second family had 2 sisters, aged 16 and 17 years, with myelodysplasia and monos | [
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omim | https://www.omim.org/entry/252270 | YNNWRxG | MONOSOMY 7 OF BONE MARROW | C1854978 | 31,748 | monosomy 7 of bone marrow. bone marrow monosomy 7. The first family was ascertained through a 6-year-old girl with AML and bone marrow monosomy 7. Her 5-year-old brother, who shared HLA antigens, was found during evaluation for donation of bone marrow to have mild thrombocytopenia, erythrocyte macrocytosis, and a minor subpopulation of bone marrow cells with monosomy 7. He went on to develop AML. The second family had 2 sisters, aged 16 and 17 years, with myelodysplasia and monosomy 7. The third family, like the first, was ascertained through a child with AML and monosomy 7 whose brother was found to have bone marrow monosomy 7 when he was evaluated as a possible transplant donor. Gilchrist et al. (1990) described 2 brothers, aged 3 and 5 years, with myelodysplasia and leukemia syndrome associated with monosomy 7. Since bone marrow transplantation is the only effective treatment of MLSM7, the | [
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omim | https://www.omim.org/entry/252270 | YNNWRxG | MONOSOMY 7 OF BONE MARROW | C1854978 | 31,748 | monosomy 7 of bone marrow. and 17 years, with myelodysplasia and monosomy 7. The third family, like the first, was ascertained through a child with AML and monosomy 7 whose brother was found to have bone marrow monosomy 7 when he was evaluated as a possible transplant donor. Gilchrist et al. (1990) described 2 brothers, aged 3 and 5 years, with myelodysplasia and leukemia syndrome associated with monosomy 7. Since bone marrow transplantation is the only effective treatment of MLSM7, the familial occurrence should be kept in mind when searching for a donor. Kwong et al. (2000) described a family with 3 sibs affected by AML in whom monosomy 7 was demonstrated. The family showed several unusual features, including the late onset of AML (34 and 37 years of age in 2 of the sibs) and the presence of an antecedent myelodysplastic phase before leukemia developed. By fluorescence in situ hybridization, the monosomy 7 clone was | [
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omim | https://www.omim.org/entry/252270 | YNNWRxG | MONOSOMY 7 OF BONE MARROW | C1854978 | 31,748 | monosomy 7 of bone marrow. only effective treatment of MLSM7, the familial occurrence should be kept in mind when searching for a donor. Kwong et al. (2000) described a family with 3 sibs affected by AML in whom monosomy 7 was demonstrated. The family showed several unusual features, including the late onset of AML (34 and 37 years of age in 2 of the sibs) and the presence of an antecedent myelodysplastic phase before leukemia developed. By fluorescence in situ hybridization, the monosomy 7 clone was shown to be capable of partial maturation, which was consistent with the biologic behavior of myelodysplasia. They pointed to the earlier report of Mitelman and Heim (1992), and the reports of familial cases by Larsen and Schimke (1976), Chitambar et al. (1983), Carroll et al. (1985), and Paul et al. (1987), among others. Minelli et al | [
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omim | https://www.omim.org/entry/252270 | YNNWRxG | MONOSOMY 7 OF BONE MARROW | C1854978 | 31,748 | monosomy 7 of bone marrow. situ hybridization, the monosomy 7 clone was shown to be capable of partial maturation, which was consistent with the biologic behavior of myelodysplasia. They pointed to the earlier report of Mitelman and Heim (1992), and the reports of familial cases by Larsen and Schimke (1976), Chitambar et al. (1983), Carroll et al. (1985), and Paul et al. (1987), among others. Minelli et al. (2001) described 2 sisters with a myelodysplastic syndrome associated with partial monosomy 7. Trisomy 8 was also present in 1 of the sisters, who later developed acute myeloid leukemia of the M0 FAB-type and died, whereas the other sister died with no evolution into AML. The authors found that the parental origin of the deleted chromosome 7 was different in the 2 sisters, thus confirming that familial monosomy 7 is not explained by a germline | [
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omim | https://www.omim.org/entry/252270 | YNNWRxG | MONOSOMY 7 OF BONE MARROW | C1854978 | 31,748 | monosomy 7 of bone marrow. , among others. Minelli et al. (2001) described 2 sisters with a myelodysplastic syndrome associated with partial monosomy 7. Trisomy 8 was also present in 1 of the sisters, who later developed acute myeloid leukemia of the M0 FAB-type and died, whereas the other sister died with no evolution into AML. The authors found that the parental origin of the deleted chromosome 7 was different in the 2 sisters, thus confirming that familial monosomy 7 is not explained by a germline mutation of a possible tumor suppressor gene. Similar results were obtained in 2 other families of the 12 reported in the literature. Noteworthy was the association with a mendelian disorder in 3 of the 12 monosomy 7 families, which suggested that a mutator gene, capable of inducing both karyotype instability and a mendelian disorder, may act to induce chromosome 7 anomalies in the marrow.
Mapping
Reasoning along the lines of the Knudson model of oncogenesis, Shannon et | [
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omim | https://www.omim.org/entry/252270 | YNNWRxG | MONOSOMY 7 OF BONE MARROW | C1854978 | 31,748 | monosomy 7 of bone marrow. monosomy 7 is not explained by a germline mutation of a possible tumor suppressor gene. Similar results were obtained in 2 other families of the 12 reported in the literature. Noteworthy was the association with a mendelian disorder in 3 of the 12 monosomy 7 families, which suggested that a mutator gene, capable of inducing both karyotype instability and a mendelian disorder, may act to induce chromosome 7 anomalies in the marrow.
Mapping
Reasoning along the lines of the Knudson model of oncogenesis, Shannon et al. (1989) used probes that mapped to chromosome 7q22-q34 to investigate 3 families with monosomy 7. It was demonstrated that different parental chromosomes 7 were retained in the leukemic bone marrows of the sibs of these families; thus, a familial predisposition to myelodysplasia could not be located within the consistently deleted segment. In the first family studied, markers on proximal 7q showed that the leukemic chromosome 7 came from the mother in both | [
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omim | https://www.omim.org/entry/252270 | YNNWRxG | MONOSOMY 7 OF BONE MARROW | C1854978 | 31,748 | monosomy 7 of bone marrow. model of oncogenesis, Shannon et al. (1989) used probes that mapped to chromosome 7q22-q34 to investigate 3 families with monosomy 7. It was demonstrated that different parental chromosomes 7 were retained in the leukemic bone marrows of the sibs of these families; thus, a familial predisposition to myelodysplasia could not be located within the consistently deleted segment. In the first family studied, markers on proximal 7q showed that the leukemic chromosome 7 came from the mother in both sibs, but in 1 sib a somatic recombination had occurred, resulting in paternal derivation of the distal part of 7q in leukemic cells. In further studies of 3 pairs of sibs, Shannon et al. (1992) found no overlapping region where all 3 pairs retained DNA derived from the same paternal or maternal chromosome, suggesting that there may not be a familial disposition to the disorder resulting from germline events. However, the findings suggested that there may | [
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] |
omim | https://www.omim.org/entry/252270 | YNNWRxG | MONOSOMY 7 OF BONE MARROW | C1854978 | 31,748 | monosomy 7 of bone marrow. leukemic chromosome 7 came from the mother in both sibs, but in 1 sib a somatic recombination had occurred, resulting in paternal derivation of the distal part of 7q in leukemic cells. In further studies of 3 pairs of sibs, Shannon et al. (1992) found no overlapping region where all 3 pairs retained DNA derived from the same paternal or maternal chromosome, suggesting that there may not be a familial disposition to the disorder resulting from germline events. However, the findings suggested that there may be multiple somatic events involving 7q in the pathogenesis of myelodysplasia.
Molecular Genetics
Using microarray-based comparative genomic hybridization (CGH) analysis, Asou et al. (2009) identified a common microdeletion involving chromosome 7q21.2-q21.3 in 8 of 21 JMML patients with normal karyotype. The microdeletion was verified by quantitative PCR analysis and involved 3 contiguous genes, SAMD9 (610456), SAM | [
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] |
omim | https://www.omim.org/entry/252270 | YNNWRxG | MONOSOMY 7 OF BONE MARROW | C1854978 | 31,748 | monosomy 7 of bone marrow. . However, the findings suggested that there may be multiple somatic events involving 7q in the pathogenesis of myelodysplasia.
Molecular Genetics
Using microarray-based comparative genomic hybridization (CGH) analysis, Asou et al. (2009) identified a common microdeletion involving chromosome 7q21.2-q21.3 in 8 of 21 JMML patients with normal karyotype. The microdeletion was verified by quantitative PCR analysis and involved 3 contiguous genes, SAMD9 (610456), SAMD9L (611170), and HEPACAM2 (614133). These 3 genes were heterozygously deleted at high frequency in both adult and childhood myeloid leukemia and were commonly lost with larger deletions of chromosome 7 in 15 of 61 adult MDS/AML patients. Nikoloski et al. (2010) identified heterozygous acquired (somatic) deletions and at chromosome 7q36.1 encompassing the EZH2 (601573) | [
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omim | https://www.omim.org/entry/252270 | YNNWRxG | MONOSOMY 7 OF BONE MARROW | C1854978 | 31,748 | monosomy 7 of bone marrow. 9 (610456), SAMD9L (611170), and HEPACAM2 (614133). These 3 genes were heterozygously deleted at high frequency in both adult and childhood myeloid leukemia and were commonly lost with larger deletions of chromosome 7 in 15 of 61 adult MDS/AML patients. Nikoloski et al. (2010) identified heterozygous acquired (somatic) deletions and at chromosome 7q36.1 encompassing the EZH2 (601573) and CUL1 (603134) genes in bone marrow cells derived from 13 of 102 individuals with myelodysplastic syndromes, including refractory anemia (RA). Two additional affected individuals had uniparental disomy (UPD) of this region. Genomic analysis of the remaining allele in 1 patient showed no aberrations in CUL1, but a truncating mutation in EZH2. Further sequencing of the EZH2 gene identified somatic mutations in 8 (26%) of 126 | [
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omim | https://www.omim.org/entry/252270 | YNNWRxG | MONOSOMY 7 OF BONE MARROW | C1854978 | 31,748 | monosomy 7 of bone marrow. encompassing the EZH2 (601573) and CUL1 (603134) genes in bone marrow cells derived from 13 of 102 individuals with myelodysplastic syndromes, including refractory anemia (RA). Two additional affected individuals had uniparental disomy (UPD) of this region. Genomic analysis of the remaining allele in 1 patient showed no aberrations in CUL1, but a truncating mutation in EZH2. Further sequencing of the EZH2 gene identified somatic mutations in 8 (26%) of 126 individuals, including the original 102 individuals. Three individuals had biallelic mutations. Collectively, 23% of affected individuals had deletions and/or point mutations in the EZH2 gene, and 40% of these individuals also had defects in the TET2 gene (612839). Individuals with defects at chromosome 7q showed significantly worse survival compared to those without these defects. The findings suggested that EZH2 may act as a tumor suppressor gene in some cases, | [
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omim | https://www.omim.org/entry/252270 | YNNWRxG | MONOSOMY 7 OF BONE MARROW | C1854978 | 31,748 | monosomy 7 of bone marrow. mutations in 8 (26%) of 126 individuals, including the original 102 individuals. Three individuals had biallelic mutations. Collectively, 23% of affected individuals had deletions and/or point mutations in the EZH2 gene, and 40% of these individuals also had defects in the TET2 gene (612839). Individuals with defects at chromosome 7q showed significantly worse survival compared to those without these defects. The findings suggested that EZH2 may act as a tumor suppressor gene in some cases, and likely influences epigenetic modifications that may lead to cancer, since EZH2 functions as a histone methyltransferase. Ernst et al. (2010) found that 9 of 12 individuals with myelodysplastic/myeloproliferative neoplasms and acquired UPD encompassing chromosome 7q36 also had a homozygous EZH2 mutation. Further sequencing of 614 individuals with myeloid disorders revealed 49 monoallelic or biallelic EZH2 mutations in 42 individuals; the mutations were found most commonly in those with | [
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omim | https://www.omim.org/entry/252270 | YNNWRxG | MONOSOMY 7 OF BONE MARROW | C1854978 | 31,748 | monosomy 7 of bone marrow. as a tumor suppressor gene in some cases, and likely influences epigenetic modifications that may lead to cancer, since EZH2 functions as a histone methyltransferase. Ernst et al. (2010) found that 9 of 12 individuals with myelodysplastic/myeloproliferative neoplasms and acquired UPD encompassing chromosome 7q36 also had a homozygous EZH2 mutation. Further sequencing of 614 individuals with myeloid disorders revealed 49 monoallelic or biallelic EZH2 mutations in 42 individuals; the mutations were found most commonly in those with myelodysplastic/myeloproliferative neoplasms (27 of 219, 12%) and in those with myelofibrosis (4 of 30, 13%). Several patients had refractory anemia, suggesting that somatic acquisition of these abnormalities may be an early event in the disease process. The mutations identified resulted in premature chain termination or direct abrogation of histone methyltransferase activity, suggesting that EZH2 can act as a tumor suppressor for myeloid malignancies. Makishima et al. (2010 | [
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omim | https://www.omim.org/entry/252270 | YNNWRxG | MONOSOMY 7 OF BONE MARROW | C1854978 | 31,748 | monosomy 7 of bone marrow. the mutations were found most commonly in those with myelodysplastic/myeloproliferative neoplasms (27 of 219, 12%) and in those with myelofibrosis (4 of 30, 13%). Several patients had refractory anemia, suggesting that somatic acquisition of these abnormalities may be an early event in the disease process. The mutations identified resulted in premature chain termination or direct abrogation of histone methyltransferase activity, suggesting that EZH2 can act as a tumor suppressor for myeloid malignancies. Makishima et al. (2010) analyzed the EZH2 gene in 344 patients with myeloid malignancies, of whom 15 had UDP7q, 30 had del(7q), and 299 had no loss of heterozygosity of chromosome 7. They found 4 different EZH2 mutations in 3 (20%) of 15 patients with UDP7q and in 2 (7%) of 30 patients with del(7q); in 1 patient without LOH7q, a heterozygous frameshift mutation was identified | [
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] |
omim | https://www.omim.org/entry/252270 | YNNWRxG | MONOSOMY 7 OF BONE MARROW | C1854978 | 31,748 | monosomy 7 of bone marrow. . Makishima et al. (2010) analyzed the EZH2 gene in 344 patients with myeloid malignancies, of whom 15 had UDP7q, 30 had del(7q), and 299 had no loss of heterozygosity of chromosome 7. They found 4 different EZH2 mutations in 3 (20%) of 15 patients with UDP7q and in 2 (7%) of 30 patients with del(7q); in 1 patient without LOH7q, a heterozygous frameshift mutation was identified. All were somatic mutations located in exon 18 or 19, coding for the SET domain of the EZH2 gene.
History
The occurrence of mosaicism for trisomy 7 in normal tissues (kidney, liver, brain), as found by Mittelman (1989), is noteworthy, as is the occurrence of uniparental disomy involving chromosome 7 and leading to cystic fibrosis (see 219700).
Inheritance
- ?Autosomal recessive
Lab
- Bone marrow | [
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omim | https://www.omim.org/entry/252270 | YNNWRxG | MONOSOMY 7 OF BONE MARROW | C1854978 | 31,748 | monosomy 7 of bone marrow. 7q, a heterozygous frameshift mutation was identified. All were somatic mutations located in exon 18 or 19, coding for the SET domain of the EZH2 gene.
History
The occurrence of mosaicism for trisomy 7 in normal tissues (kidney, liver, brain), as found by Mittelman (1989), is noteworthy, as is the occurrence of uniparental disomy involving chromosome 7 and leading to cystic fibrosis (see 219700).
Inheritance
- ?Autosomal recessive
Lab
- Bone marrow monosomy 7 or deletion of the long arm of chromosome 7 (7q22-q34)
Heme
- Myelodysplasia and acute myelogenous leukemia (AML)
- Thrombocytopenia
- Erythrocyte macrocytosis
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orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=230851 | 7Rgwomn | Cardiac-valvular Ehlers-Danlos syndrome | C1857034 | 31,749 | cardiac-valvular ehlers-danlos syndrome. A rare form of Ehlers-Danlos syndrome (EDS) characterized by soft skin, skin hyperextensibility, easy bruisability, atrophic scar formation, joint hypermobility and severe, progressive cardiac valvular defects comprising mitral and/or aortic valve insufficiency. | [
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wikipedia | https://en.wikipedia.org/wiki/Sch%C3%B6pf%E2%80%93Schulz%E2%80%93Passarge_syndrome | D4orkjY | Schöpf–Schulz–Passarge syndrome | C1857069 | 31,750 | schöpf–schulz–passarge syndrome. Schöpf–Schulz–Passarge syndromeOther namesEyelid cysts, Palmoplantar keratoderma, Hypodontia, and HypotrichosisSpecialtyMedical genetics
Schöpf–Schulz–Passarge syndrome is an autosomal recessive condition with punctate symmetric palmoplantar keratoderma, with the keratoderma and fragility of the nails beginning around age 12.:513 In addition to palmoplantar keratoderma, other symptoms include hypodontia, hypotrichosis, nail dystrophies, and eyelid cysts (apocrine hidrocystomas). Patients may also develop syringofibroadenoma and squamous cell carcinomas.
It was characterized in 1971.
It has been associated with WNT10A.
See also
Palmoplantar keratoderma
List of cutaneous conditions
List of dental abnormalities associated with cutaneous conditions
List of cutaneous neoplasms associated with systemic syndromes
References
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wikipedia | https://en.wikipedia.org/wiki/Sch%C3%B6pf%E2%80%93Schulz%E2%80%93Passarge_syndrome | D4orkjY | Schöpf–Schulz–Passarge syndrome | C1857069 | 31,750 | schöpf–schulz–passarge syndrome. to palmoplantar keratoderma, other symptoms include hypodontia, hypotrichosis, nail dystrophies, and eyelid cysts (apocrine hidrocystomas). Patients may also develop syringofibroadenoma and squamous cell carcinomas.
It was characterized in 1971.
It has been associated with WNT10A.
See also
Palmoplantar keratoderma
List of cutaneous conditions
List of dental abnormalities associated with cutaneous conditions
List of cutaneous neoplasms associated with systemic syndromes
References
^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser- | [
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wikipedia | https://en.wikipedia.org/wiki/Sch%C3%B6pf%E2%80%93Schulz%E2%80%93Passarge_syndrome | D4orkjY | Schöpf–Schulz–Passarge syndrome | C1857069 | 31,750 | schöpf–schulz–passarge syndrome. conditions
List of cutaneous neoplasms associated with systemic syndromes
References
^ Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .id-lock-free a,.mw-parser-output .citation .cs1-lock-free a{background:linear-gradient(transparent,transparent),url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no- | [
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wikipedia | https://en.wikipedia.org/wiki/Sch%C3%B6pf%E2%80%93Schulz%E2%80%93Passarge_syndrome | D4orkjY | Schöpf–Schulz–Passarge syndrome | C1857069 | 31,750 | schöpf–schulz–passarge syndrome. citation .cs1-lock-subscription a{background:linear-gradient(transparent,transparent),url("//upload.wikimedia.org/wikipedia/commons/a/aa/Lock-red-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-ws-icon a{background:linear-gradient(transparent,transparent),url("/ | [
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wikipedia | https://en.wikipedia.org/wiki/Sch%C3%B6pf%E2%80%93Schulz%E2%80%93Passarge_syndrome | D4orkjY | Schöpf–Schulz–Passarge syndrome | C1857069 | 31,750 | schöpf–schulz–passarge syndrome. it;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-right,.mw-parser-output .cs1-kern | [
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wikipedia | https://en.wikipedia.org/wiki/Sch%C3%B6pf%E2%80%93Schulz%E2%80%93Passarge_syndrome | D4orkjY | Schöpf–Schulz–Passarge syndrome | C1857069 | 31,750 | schöpf–schulz–passarge syndrome. ;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}ISBN 0-07-138076-0.
^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology | [
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wikipedia | https://en.wikipedia.org/wiki/Sch%C3%B6pf%E2%80%93Schulz%E2%80%93Passarge_syndrome | D4orkjY | Schöpf–Schulz–Passarge syndrome | C1857069 | 31,750 | schöpf–schulz–passarge syndrome. right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}ISBN 0-07-138076-0.
^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 778. ISBN 978-1-4160-2999-1.
^ Calonje, Eduardo (2012). Mckee's Pathology of the Skin: With Clinical Correlations. Elsevier/Saunders.
^ Schöpf E, Schulz HJ, Passarge E (June 1971 | [
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wikipedia | https://en.wikipedia.org/wiki/Sch%C3%B6pf%E2%80%93Schulz%E2%80%93Passarge_syndrome | D4orkjY | Schöpf–Schulz–Passarge syndrome | C1857069 | 31,750 | schöpf–schulz–passarge syndrome. rizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 778. ISBN 978-1-4160-2999-1.
^ Calonje, Eduardo (2012). Mckee's Pathology of the Skin: With Clinical Correlations. Elsevier/Saunders.
^ Schöpf E, Schulz HJ, Passarge E (June 1971). "Syndrome of cystic eyelids, palmo-plantar keratosis, hypodontia and hypotrichosis as a possible autosomal recessive trait". Birth Defects Orig. Artic. Ser. 7 (8): 219–21. PMID 4281327.
^ Bohring A, Stamm T, Spaich C, et al. (July 2009). "WNT10A mutations are a frequent | [
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wikipedia | https://en.wikipedia.org/wiki/Sch%C3%B6pf%E2%80%93Schulz%E2%80%93Passarge_syndrome | D4orkjY | Schöpf–Schulz–Passarge syndrome | C1857069 | 31,750 | schöpf–schulz–passarge syndrome. E, Schulz HJ, Passarge E (June 1971). "Syndrome of cystic eyelids, palmo-plantar keratosis, hypodontia and hypotrichosis as a possible autosomal recessive trait". Birth Defects Orig. Artic. Ser. 7 (8): 219–21. PMID 4281327.
^ Bohring A, Stamm T, Spaich C, et al. (July 2009). "WNT10A mutations are a frequent cause of a broad spectrum of ectodermal dysplasias with sex-biased manifestation pattern in heterozygotes". Am. J. Hum. Genet. 85 (1): 97–105. doi:10.1016/j.ajhg.2009.06.001. PMC 2706962. PMID 19559398.
External links
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] |
wikipedia | https://en.wikipedia.org/wiki/Sch%C3%B6pf%E2%80%93Schulz%E2%80%93Passarge_syndrome | D4orkjY | Schöpf–Schulz–Passarge syndrome | C1857069 | 31,750 | schöpf–schulz–passarge syndrome. . (July 2009). "WNT10A mutations are a frequent cause of a broad spectrum of ectodermal dysplasias with sex-biased manifestation pattern in heterozygotes". Am. J. Hum. Genet. 85 (1): 97–105. doi:10.1016/j.ajhg.2009.06.001. PMC 2706962. PMID 19559398.
External links
ClassificationDICD-10: Q82.8OMIM: 224750MeSH: C565607
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wikipedia | https://en.wikipedia.org/wiki/Sch%C3%B6pf%E2%80%93Schulz%E2%80%93Passarge_syndrome | D4orkjY | Schöpf–Schulz–Passarge syndrome | C1857069 | 31,750 | schöpf–schulz–passarge syndrome. DICD-10: Q82.8OMIM: 224750MeSH: C565607
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wikipedia | https://en.wikipedia.org/wiki/Sch%C3%B6pf%E2%80%93Schulz%E2%80%93Passarge_syndrome | D4orkjY | Schöpf–Schulz–Passarge syndrome | C1857069 | 31,750 | schöpf–schulz–passarge syndrome. bar-ct-full{font-size:114%;margin:0 7em}.mw-parser-output .navbar-ct-mini{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}vte
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wikipedia | https://en.wikipedia.org/wiki/Sch%C3%B6pf%E2%80%93Schulz%E2%80%93Passarge_syndrome | D4orkjY | Schöpf–Schulz–Passarge syndrome | C1857069 | 31,750 | schöpf–schulz–passarge syndrome. :block;font-size:100%}.mw-parser-output .navbox-title .navbar{float:left;text-align:left;margin-right:0.5em}vte
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wikipedia | https://en.wikipedia.org/wiki/Sch%C3%B6pf%E2%80%93Schulz%E2%80%93Passarge_syndrome | D4orkjY | Schöpf–Schulz–Passarge syndrome | C1857069 | 31,750 | schöpf–schulz–passarge syndrome. ‐expand size: 16916/5000000 bytes
Lua time usage: 0.130/10.000 seconds
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Number of Wikibase entities loaded: 1/400
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wikipedia | https://en.wikipedia.org/wiki/Sch%C3%B6pf%E2%80%93Schulz%E2%80%93Passarge_syndrome | D4orkjY | Schöpf–Schulz–Passarge syndrome | C1857069 | 31,750 | schöpf–schulz–passarge syndrome. 42.19% 157.833 1 Template:Reflist
35.84% 134.079 2 Template:Infobox
26.97% 100.915 1 Template:Infobox_medical_condition_(new)
18.15% 67.886 2 Template:Cite_book
17.82% 66.677 1 Template:ISBN
17.10% 63.980 1 Template:Medical_resources
12.77% 47.766 1 Template:Catalog_lookup_link
11.58% 43.309 2 Template:Hlist
8.54% 31.955 1 Template:Cutaneous-condition-stub
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wikipedia | https://en.wikipedia.org/wiki/Sch%C3%B6pf%E2%80%93Schulz%E2%80%93Passarge_syndrome | D4orkjY | Schöpf–Schulz–Passarge syndrome | C1857069 | 31,750 | schöpf–schulz–passarge syndrome. :Medical_resources
12.77% 47.766 1 Template:Catalog_lookup_link
11.58% 43.309 2 Template:Hlist
8.54% 31.955 1 Template:Cutaneous-condition-stub
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] |
omim | https://www.omim.org/entry/225280 | P0Zrv91 | ECTODERMAL DYSPLASIA, ECTRODACTYLY, AND MACULAR DYSTROPHY SYNDROME | C1857041 | 31,751 | ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome. A number sign (#) is used with this entry because of evidence that EEM syndrome (EEMS) is caused by homozygous mutation in the CDH3 gene (114021) on chromosome 16q22.
Clinical Features
In an isolated population on a remote island in Japan, Ohdo et al. (1983) observed a kindred with 6 cases of ectodermal dysplasia, ectrodactyly associated with syndactyly or cleft hand or both, and macular dystrophy which was presumed to be progressive. Because of the parental consanguinity and the occurrence in both sexes, autosomal recessive inheritance was suggested. The presence of macular dystrophy distinguishes it from other syndromes of ectodermal dysplasia and limb malformations. The same disorder was probably reported by Albrectsen and Svendsen (1956) in the son and daughter of first-cousin parents and by Hayakawa et al. (1979) in a 30-year-old | [
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omim | https://www.omim.org/entry/225280 | P0Zrv91 | ECTODERMAL DYSPLASIA, ECTRODACTYLY, AND MACULAR DYSTROPHY SYNDROME | C1857041 | 31,751 | ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome. cleft hand or both, and macular dystrophy which was presumed to be progressive. Because of the parental consanguinity and the occurrence in both sexes, autosomal recessive inheritance was suggested. The presence of macular dystrophy distinguishes it from other syndromes of ectodermal dysplasia and limb malformations. The same disorder was probably reported by Albrectsen and Svendsen (1956) in the son and daughter of first-cousin parents and by Hayakawa et al. (1979) in a 30-year-old woman whose parents were first cousins. Kuster et al. (1987) considered the disorder in the single affected case they described to be distinct. Balarin Silva et al. (1999) reported a Brazilian kindred in which 2 sibs exhibited the complete form of EEM, with hypotrichosis, dental anomalies, syndactyly, and retinal changes with prominent pigmentation in the posterior pole of the retina. | [
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omim | https://www.omim.org/entry/225280 | P0Zrv91 | ECTODERMAL DYSPLASIA, ECTRODACTYLY, AND MACULAR DYSTROPHY SYNDROME | C1857041 | 31,751 | ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome. akawa et al. (1979) in a 30-year-old woman whose parents were first cousins. Kuster et al. (1987) considered the disorder in the single affected case they described to be distinct. Balarin Silva et al. (1999) reported a Brazilian kindred in which 2 sibs exhibited the complete form of EEM, with hypotrichosis, dental anomalies, syndactyly, and retinal changes with prominent pigmentation in the posterior pole of the retina. Another sib exhibited minimal symptoms, consisting of mild bilateral syndactyly between fingers 1, 2, 3, and 4 and small, widely spaced teeth, whereas his ophthalmologic and hair examination were unremarkable. A first cousin also had ectrodactyly of the right hand (lobster-claw deformity) but no dental, dermatologic, or ocular abnormalities. Balarin Silva et al. (1999) followed the | [
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omim | https://www.omim.org/entry/225280 | P0Zrv91 | ECTODERMAL DYSPLASIA, ECTRODACTYLY, AND MACULAR DYSTROPHY SYNDROME | C1857041 | 31,751 | ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome. , and retinal changes with prominent pigmentation in the posterior pole of the retina. Another sib exhibited minimal symptoms, consisting of mild bilateral syndactyly between fingers 1, 2, 3, and 4 and small, widely spaced teeth, whereas his ophthalmologic and hair examination were unremarkable. A first cousin also had ectrodactyly of the right hand (lobster-claw deformity) but no dental, dermatologic, or ocular abnormalities. Balarin Silva et al. (1999) followed the sibs with EEM for 10 years, observing gradually decreasing visual acuity and progression of retinal degenerative anomalies. Senecky et al. (2001) described a brother and sister with ectodermal dysplasia, ectrodactyly, and macular dystrophy. Both children had abnormalities of the hands and the hair as well as bilateral macular degeneration. The clinical picture in both was similar to, but milder than, that described in the previously reported | [
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omim | https://www.omim.org/entry/225280 | P0Zrv91 | ECTODERMAL DYSPLASIA, ECTRODACTYLY, AND MACULAR DYSTROPHY SYNDROME | C1857041 | 31,751 | ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome. ocular abnormalities. Balarin Silva et al. (1999) followed the sibs with EEM for 10 years, observing gradually decreasing visual acuity and progression of retinal degenerative anomalies. Senecky et al. (2001) described a brother and sister with ectodermal dysplasia, ectrodactyly, and macular dystrophy. Both children had abnormalities of the hands and the hair as well as bilateral macular degeneration. The clinical picture in both was similar to, but milder than, that described in the previously reported cases of EEMS. The parents were not related, but were of Jewish Yemenite origin.
Molecular Genetics
In affected individuals with EEMS from the Danish family reported by Albrectsen and Svendsen (1956) and from the Brazilian family reported by Balarin Silva et al. (1999), Kjaer et al. (2005) identified homozygosity for mutations in CDH3: a missense mutation ( | [
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] |
omim | https://www.omim.org/entry/225280 | P0Zrv91 | ECTODERMAL DYSPLASIA, ECTRODACTYLY, AND MACULAR DYSTROPHY SYNDROME | C1857041 | 31,751 | ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome. both was similar to, but milder than, that described in the previously reported cases of EEMS. The parents were not related, but were of Jewish Yemenite origin.
Molecular Genetics
In affected individuals with EEMS from the Danish family reported by Albrectsen and Svendsen (1956) and from the Brazilian family reported by Balarin Silva et al. (1999), Kjaer et al. (2005) identified homozygosity for mutations in CDH3: a missense mutation (114021.0003) and a deletion (114021.0004), respectively. The minimally symptomatic brother of the proband in the Brazilian family was found to be heterozygous for the deletion mutation.
INHERITANCE
- Autosomal recessive
HEAD & NECK
Eyes
- Sparse eyebrows
- Sparse eyelashes
- Macular dystrophy
Teeth
- Small teeth
- Widely spaced teeth
- Selective tooth agenesis
SKELETAL
Hands
- Ectrodactyly
- Syndactyly
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] |
omim | https://www.omim.org/entry/225280 | P0Zrv91 | ECTODERMAL DYSPLASIA, ECTRODACTYLY, AND MACULAR DYSTROPHY SYNDROME | C1857041 | 31,751 | ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome. 2005) identified homozygosity for mutations in CDH3: a missense mutation (114021.0003) and a deletion (114021.0004), respectively. The minimally symptomatic brother of the proband in the Brazilian family was found to be heterozygous for the deletion mutation.
INHERITANCE
- Autosomal recessive
HEAD & NECK
Eyes
- Sparse eyebrows
- Sparse eyelashes
- Macular dystrophy
Teeth
- Small teeth
- Widely spaced teeth
- Selective tooth agenesis
SKELETAL
Hands
- Ectrodactyly
- Syndactyly
- Camptodactyly
SKIN, NAILS, & HAIR
Skin
- Normal sweating
Hair
- Sparse scalp hair
- Sparse eyebrows
- Sparse eyelashes
MOLECULAR BASIS
- Caused by mutation in the cadherin 3 gene (CDH3,
114021.0003
)
▲ Close | [
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] |
omim | https://www.omim.org/entry/225280 | P0Zrv91 | ECTODERMAL DYSPLASIA, ECTRODACTYLY, AND MACULAR DYSTROPHY SYNDROME | C1857041 | 31,751 | ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome. - Selective tooth agenesis
SKELETAL
Hands
- Ectrodactyly
- Syndactyly
- Camptodactyly
SKIN, NAILS, & HAIR
Skin
- Normal sweating
Hair
- Sparse scalp hair
- Sparse eyebrows
- Sparse eyelashes
MOLECULAR BASIS
- Caused by mutation in the cadherin 3 gene (CDH3,
114021.0003
)
▲ Close | [
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orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=50944 | lgR2rrz | Schöpf-Schulz-Passarge syndrome | C1857069 | 31,752 | schöpf-schulz-passarge syndrome. Schöpf-Schulz-Passarge syndrome (SSPS) is a rare autosomal recessive ectodermal dysplasia characterized by multiple eyelid apocrine hidrocystomas, palmoplantar keratoderma, hypotrichosis, hypodontia and nail dystrophy.
Epidemiology
More than 25 cases with SSPS have been described so far.
Clinical description
SSPS refers to a discrete phenotype of ectodermal dysplasia with a relatively benign course and late diagnosis, often established in adulthood. The onset of symptoms occurs in childhood and early adolescence, but they consist of relatively unspecific features, including various degrees of hypodontia, hypotrichosis, palmoplantar keratoderma and nail dystrophy. Telangiectatic rosacea is a further relatively common feature. Multiple eyelid apocrine hidrocystomas commonly appear in (late) adulthood. Palmoplantar keratoderma with histologic features of eccrine syringofibroadenoma is observed in nearly | [
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orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=50944 | lgR2rrz | Schöpf-Schulz-Passarge syndrome | C1857069 | 31,752 | schöpf-schulz-passarge syndrome. and late diagnosis, often established in adulthood. The onset of symptoms occurs in childhood and early adolescence, but they consist of relatively unspecific features, including various degrees of hypodontia, hypotrichosis, palmoplantar keratoderma and nail dystrophy. Telangiectatic rosacea is a further relatively common feature. Multiple eyelid apocrine hidrocystomas commonly appear in (late) adulthood. Palmoplantar keratoderma with histologic features of eccrine syringofibroadenoma is observed in nearly half of cases and occasionally develops a malignant potential. Other adnexal tumors described include basal cell carcinoma, eccrine poroma, benign acanthoma and follicular infundibulum tumor. Some patients have been described to have a bird-like facies. Within the WNT10A mutational spectrum, odonto-onycho-dermal dysplasia and SSPS are regarded as discrete entities, while an increasing number of patients are described with incomplete phenotypes | [
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orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=50944 | lgR2rrz | Schöpf-Schulz-Passarge syndrome | C1857069 | 31,752 | schöpf-schulz-passarge syndrome. histologic features of eccrine syringofibroadenoma is observed in nearly half of cases and occasionally develops a malignant potential. Other adnexal tumors described include basal cell carcinoma, eccrine poroma, benign acanthoma and follicular infundibulum tumor. Some patients have been described to have a bird-like facies. Within the WNT10A mutational spectrum, odonto-onycho-dermal dysplasia and SSPS are regarded as discrete entities, while an increasing number of patients are described with incomplete phenotypes of the odonto-onychial, tricho-odonto and tricho-odonto-onychial types.
Etiology
SSPS is due to homozygous or compound heterozygous mutations in WNT10A. Incomplete/localized disease expression in heterozygous carriers and multiple instances of consanguinity occasionally lead to a pseudodominant transmission.
Genetic counseling
Transmission is autosomal recessive. | [
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orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=50944 | lgR2rrz | Schöpf-Schulz-Passarge syndrome | C1857069 | 31,752 | schöpf-schulz-passarge syndrome. discrete entities, while an increasing number of patients are described with incomplete phenotypes of the odonto-onychial, tricho-odonto and tricho-odonto-onychial types.
Etiology
SSPS is due to homozygous or compound heterozygous mutations in WNT10A. Incomplete/localized disease expression in heterozygous carriers and multiple instances of consanguinity occasionally lead to a pseudodominant transmission.
Genetic counseling
Transmission is autosomal recessive. | [
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omim | https://www.omim.org/entry/300378 | zyRyL7L | RADIAL RAY DEFICIENCY, X-LINKED | C1845717 | 31,753 | radial ray deficiency, x-linked. Clinical Features
Galjaard et al. (2001) reported a family of Turkish origin with 4 male relatives showing bilateral radial aplasia with presence of the thumbs and associated anomalies. The index patient showed absence of the radii, broad curved ulnae, hypoplasia of the thumbs, Dandy-Walker malformation, transposition of the great arteries, and an atrial septal defect. A male first cousin with short stature showed the same anomalies of the upper extremities with extension deficit of the second to fourth metacarpophalangeal joints of both hands. His lower extremities showed abducted hip joints and contractures of both knees with absence of the patellae. Two maternal uncles were affected with similar anomalies of the upper extremities. The differential diagnosis included VACTERLX (314390) and radial aplasia with anogenital anomalies (312190), but because of the different clinical picture Galjaard et al. (2001) suggested that | [
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omim | https://www.omim.org/entry/300378 | zyRyL7L | RADIAL RAY DEFICIENCY, X-LINKED | C1845717 | 31,753 | radial ray deficiency, x-linked. extremities with extension deficit of the second to fourth metacarpophalangeal joints of both hands. His lower extremities showed abducted hip joints and contractures of both knees with absence of the patellae. Two maternal uncles were affected with similar anomalies of the upper extremities. The differential diagnosis included VACTERLX (314390) and radial aplasia with anogenital anomalies (312190), but because of the different clinical picture Galjaard et al. (2001) suggested that their family represents a previously unreported phenotype. The authors hypothesized that the responsible gene must be involved in patterning, differentiation, or apoptosis during human embryonic limb development.
Mapping
By linkage analysis with microsatellite markers spanning the X chromosome in a family with radial ray deficiency, Galjaard et al. (2001) found a maximum lod score of 1.93 for DXS8067 and DXS1001 (at theta = 0) located in Xq24- | [
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omim | https://www.omim.org/entry/300378 | zyRyL7L | RADIAL RAY DEFICIENCY, X-LINKED | C1845717 | 31,753 | radial ray deficiency, x-linked. jaard et al. (2001) suggested that their family represents a previously unreported phenotype. The authors hypothesized that the responsible gene must be involved in patterning, differentiation, or apoptosis during human embryonic limb development.
Mapping
By linkage analysis with microsatellite markers spanning the X chromosome in a family with radial ray deficiency, Galjaard et al. (2001) found a maximum lod score of 1.93 for DXS8067 and DXS1001 (at theta = 0) located in Xq24-q25. The patients shared an identical haplotype from DXS990 to DXS1193. Two unaffected males shared part of this haplotype, and combined results of linkage and haplotype analysis suggested the responsible gene to be localized between markers DXS8055 and DXS1212. | [
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omim | https://www.omim.org/entry/300378 | zyRyL7L | RADIAL RAY DEFICIENCY, X-LINKED | C1845717 | 31,753 | radial ray deficiency, x-linked. theta = 0) located in Xq24-q25. The patients shared an identical haplotype from DXS990 to DXS1193. Two unaffected males shared part of this haplotype, and combined results of linkage and haplotype analysis suggested the responsible gene to be localized between markers DXS8055 and DXS1212. | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. SummaryClinical characteristics.Prothrombin-related thrombophilia is characterized by venous thromboembolism (VTE) manifest most commonly in adults as deep-vein thrombosis (DVT) in the legs or pulmonary embolism. The clinical expression of prothrombin-related thrombophilia is variable; many individuals heterozygous or homozygous for the 20210G>A (G20210A or c.*97G>A) allele in F2 never develop thrombosis, and while most heterozygotes who develop thrombotic complications remain asymptomatic until adulthood, some have recurrent thromboembolism before age 30 years. The relative risk for DVT in adults heterozygous for the 20210G>A allele is two- to fivefold increased; in children, the relative risk for thrombosis is three- to fourfold increased. Heterozygosity for 20210G>A has at most a modest effect on recurrence risk after a first episode. Although prothrombin-related thrombophilia may increase the risk for pregnancy loss, its association with preeclampsia and other | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. develop thrombotic complications remain asymptomatic until adulthood, some have recurrent thromboembolism before age 30 years. The relative risk for DVT in adults heterozygous for the 20210G>A allele is two- to fivefold increased; in children, the relative risk for thrombosis is three- to fourfold increased. Heterozygosity for 20210G>A has at most a modest effect on recurrence risk after a first episode. Although prothrombin-related thrombophilia may increase the risk for pregnancy loss, its association with preeclampsia and other complications of pregnancy such as intrauterine growth restriction and placental abruption remains controversial. Factors that predispose to thrombosis in prothrombin-related thrombophilia include: the number of 20210G>A alleles; presence of coexisting genetic abnormalities including factor V Leiden; and acquired thrombophilic disorders (e.g., antiphospholipid antibodies). Circumstantial risk factors for thrombosis include pregnancy and oral contraceptive use. Some evidence suggests that the risk for VTE in 20210G | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. loss, its association with preeclampsia and other complications of pregnancy such as intrauterine growth restriction and placental abruption remains controversial. Factors that predispose to thrombosis in prothrombin-related thrombophilia include: the number of 20210G>A alleles; presence of coexisting genetic abnormalities including factor V Leiden; and acquired thrombophilic disorders (e.g., antiphospholipid antibodies). Circumstantial risk factors for thrombosis include pregnancy and oral contraceptive use. Some evidence suggests that the risk for VTE in 20210G>A heterozygotes increases after travel.Diagnosis/testing.The diagnosis of prothrombin-related thrombophilia requires molecular genetic testing of F2, the gene encoding prothrombin, to identify the 20210G>A allele (also known as G20210A or c.*97G>A).Management.Treatment of manifestations: Management depends on the clinical circumstances. The first acute thrombosis is treated according to standard guidelines with a course of low | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. the risk for VTE in 20210G>A heterozygotes increases after travel.Diagnosis/testing.The diagnosis of prothrombin-related thrombophilia requires molecular genetic testing of F2, the gene encoding prothrombin, to identify the 20210G>A allele (also known as G20210A or c.*97G>A).Management.Treatment of manifestations: Management depends on the clinical circumstances. The first acute thrombosis is treated according to standard guidelines with a course of low molecular-weight heparin (LMWH) or fondaparinux, and concurrent oral administration of warfarin for at least five days (except in pregnancy). The international-normalized ratio (INR) is used to monitor warfarin anticoagulation. Rivaroxaban, a factor Xa inhibitor, is approved for the treatment of acute VTE and long-term prevention of recurrence. The duration of anticoagulation therapy is determined by assessment of the risks for (1) VTE recurrence and (2) anticoagulant | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. to standard guidelines with a course of low molecular-weight heparin (LMWH) or fondaparinux, and concurrent oral administration of warfarin for at least five days (except in pregnancy). The international-normalized ratio (INR) is used to monitor warfarin anticoagulation. Rivaroxaban, a factor Xa inhibitor, is approved for the treatment of acute VTE and long-term prevention of recurrence. The duration of anticoagulation therapy is determined by assessment of the risks for (1) VTE recurrence and (2) anticoagulant-related bleeding. Individuals with a spontaneous thrombosis with no identifiable provoking factors and those with persistent risk factors are candidates for long-term anticoagulation therapy. Treatment for three months is recommended for individuals with transient (reversible) risk factors such as surgery. Graduated compression stockings should be worn for at least two years following an acute DVT.Agents/circumstances to avoid: Heterozygous and homozygous women with a history of VTE should avoid estrogen-containing contraception and hormone replacement therapy | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. ) VTE recurrence and (2) anticoagulant-related bleeding. Individuals with a spontaneous thrombosis with no identifiable provoking factors and those with persistent risk factors are candidates for long-term anticoagulation therapy. Treatment for three months is recommended for individuals with transient (reversible) risk factors such as surgery. Graduated compression stockings should be worn for at least two years following an acute DVT.Agents/circumstances to avoid: Heterozygous and homozygous women with a history of VTE should avoid estrogen-containing contraception and hormone replacement therapy (HRT).Evaluation of relatives at risk: Because there is no clinical evidence that early diagnosis reduces morbidity or mortality, the indications for family testing are unresolved and the decision to test at-risk family members should be made on an individual basis.Pregnancy management: No consensus exists on the optimal management of prothrombin-related thrombophilia during pregnancy; guidelines for treatment of VTE are derived from studies in non-pregnant individuals.Genetic counseling.Prothrombin-related thrombophilia is | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. estrogen-containing contraception and hormone replacement therapy (HRT).Evaluation of relatives at risk: Because there is no clinical evidence that early diagnosis reduces morbidity or mortality, the indications for family testing are unresolved and the decision to test at-risk family members should be made on an individual basis.Pregnancy management: No consensus exists on the optimal management of prothrombin-related thrombophilia during pregnancy; guidelines for treatment of VTE are derived from studies in non-pregnant individuals.Genetic counseling.Prothrombin-related thrombophilia is inherited in an autosomal dominant manner: heterozygosity for the 20210G>A allele results in an increased risk for thrombosis; homozygosity for this allele confers a higher risk for thrombosis than heterozygosity. All individuals reported to date with prothrombin-related thrombophilia who are heterozygous for the 20210G>A allele have had an affected parent. Because of the relatively high prevalence of this allele in the general population, occasionally one parent is homozygous or both parents | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. counseling.Prothrombin-related thrombophilia is inherited in an autosomal dominant manner: heterozygosity for the 20210G>A allele results in an increased risk for thrombosis; homozygosity for this allele confers a higher risk for thrombosis than heterozygosity. All individuals reported to date with prothrombin-related thrombophilia who are heterozygous for the 20210G>A allele have had an affected parent. Because of the relatively high prevalence of this allele in the general population, occasionally one parent is homozygous or both parents are heterozygous for this allele. If one parent of a heterozygous proband is heterozygous for the 20210G>A allele, the sibs of the proband are at 50% risk of being heterozygous; if one parent is homozygous, the sibs of the proband will be heterozygous. Although technically possible, prenatal diagnosis and preimplantation genetic diagnosis (PGD) are rarely, if ever, performed because the 20210G>A allele only increases the relative risk | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. occasionally one parent is homozygous or both parents are heterozygous for this allele. If one parent of a heterozygous proband is heterozygous for the 20210G>A allele, the sibs of the proband are at 50% risk of being heterozygous; if one parent is homozygous, the sibs of the proband will be heterozygous. Although technically possible, prenatal diagnosis and preimplantation genetic diagnosis (PGD) are rarely, if ever, performed because the 20210G>A allele only increases the relative risk for thrombophilia and is not predictive of a thrombotic event.DiagnosisSuggestive FindingsNo clinical features are specific for prothrombin-related thrombophilia. The diagnosis is suspected in probands with at least one of the more specific features :A first unprovoked venous thromboembolism (VTE) before age 50 yearsA history of recurrent VTEVenous thrombosis at certain unusual sites such as the cerebral, mesenteric, portal, or hepatic veinsVTE during pregnancy or the puerperium | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. ;A allele only increases the relative risk for thrombophilia and is not predictive of a thrombotic event.DiagnosisSuggestive FindingsNo clinical features are specific for prothrombin-related thrombophilia. The diagnosis is suspected in probands with at least one of the more specific features :A first unprovoked venous thromboembolism (VTE) before age 50 yearsA history of recurrent VTEVenous thrombosis at certain unusual sites such as the cerebral, mesenteric, portal, or hepatic veinsVTE during pregnancy or the puerperiumVTE associated with the use of estrogen-containing oral contraceptives or hormone replacement therapy (HRT)An unprovoked VTE at any age in an individual with a first-degree family member with a VTE before age 50 yearsProthrombin-related thrombophilia may also be considered in probands who have less specific findings, including the following:A history of unprovoked VTE considering discontinuation of anticoagulation Selected women with unexplained second trimester fetal lossA first VTE related to | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. E during pregnancy or the puerperiumVTE associated with the use of estrogen-containing oral contraceptives or hormone replacement therapy (HRT)An unprovoked VTE at any age in an individual with a first-degree family member with a VTE before age 50 yearsProthrombin-related thrombophilia may also be considered in probands who have less specific findings, including the following:A history of unprovoked VTE considering discontinuation of anticoagulation Selected women with unexplained second trimester fetal lossA first VTE related to use of tamoxifen or other selective estrogen receptor modulators (SERM)Age greater than 50 years with a first unprovoked VTENeonates and children with non-catheter related idiopathic VTE or strokeTesting to Confirm the DiagnosisThe diagnosis of prothrombin-related thrombophilia requires molecular genetic analysis of F2, the gene encoding prothrombin, to identify the common pathogenic variant 20210G>A (see Table 1). Note that because the range of plasma concentrations | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. trimester fetal lossA first VTE related to use of tamoxifen or other selective estrogen receptor modulators (SERM)Age greater than 50 years with a first unprovoked VTENeonates and children with non-catheter related idiopathic VTE or strokeTesting to Confirm the DiagnosisThe diagnosis of prothrombin-related thrombophilia requires molecular genetic analysis of F2, the gene encoding prothrombin, to identify the common pathogenic variant 20210G>A (see Table 1). Note that because the range of plasma concentrations of prothrombin in heterozygotes overlaps with the normal range (see Molecular Genetics, Normal gene product), the plasma prothrombin concentration is not reliable for diagnosis.The decision to test an individual suspected of having prothrombin-related thrombophilia should be based on the likelihood that test results would influence treatment .Note: (1) Clinical guidelines from the UK and the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group stress the uncertain benefit of testing for inherited thrombophilia | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. Note that because the range of plasma concentrations of prothrombin in heterozygotes overlaps with the normal range (see Molecular Genetics, Normal gene product), the plasma prothrombin concentration is not reliable for diagnosis.The decision to test an individual suspected of having prothrombin-related thrombophilia should be based on the likelihood that test results would influence treatment .Note: (1) Clinical guidelines from the UK and the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group stress the uncertain benefit of testing for inherited thrombophilia in several accepted circumstances, including in individuals who have some of the more specific findings . See Published Guidelines / Policy Statements. (2) American and British guidelines do not recommend routine testing for thrombophilia in adults or children with VTE .Table 1. Molecular Genetic Testing Used in Prothrombin-Related ThrombophiliaView in own windowGene 1MethodVariants DetectedProportion of Probands with a Pathogenic Variant Detectable by MethodF2Targeted analysis for pathogenic variants 220 | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. uncertain benefit of testing for inherited thrombophilia in several accepted circumstances, including in individuals who have some of the more specific findings . See Published Guidelines / Policy Statements. (2) American and British guidelines do not recommend routine testing for thrombophilia in adults or children with VTE .Table 1. Molecular Genetic Testing Used in Prothrombin-Related ThrombophiliaView in own windowGene 1MethodVariants DetectedProportion of Probands with a Pathogenic Variant Detectable by MethodF2Targeted analysis for pathogenic variants 220210G>A (c.*97G>A) 3100%1. See Table A. Genes and Databases for chromosome locus and protein. See Molecular Genetics for information on allelic variants detected in this gene.2. Targeted analysis for the 20210G>A (c.*97G>A) pathogenic variant is performed by a variety of comparable methods .3. The official designation of the | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. rgeted analysis for pathogenic variants 220210G>A (c.*97G>A) 3100%1. See Table A. Genes and Databases for chromosome locus and protein. See Molecular Genetics for information on allelic variants detected in this gene.2. Targeted analysis for the 20210G>A (c.*97G>A) pathogenic variant is performed by a variety of comparable methods .3. The official designation of the pathogenic variant is c.*97G>A per guidelines at varnomen.hgvs.org.Interpretation of test results. Molecular genetic test results are reliable in individuals on warfarin, heparin, or other antithrombotic agents and are independent of thrombotic episodes.Test results on DNA extracted from peripheral blood leukocytes need to be interpreted with caution in the setting of liver transplantation or hematopoetic stem cell transplantation (HSCT).Diagnosis of prothrombin-related thrombophilia | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. 3. The official designation of the pathogenic variant is c.*97G>A per guidelines at varnomen.hgvs.org.Interpretation of test results. Molecular genetic test results are reliable in individuals on warfarin, heparin, or other antithrombotic agents and are independent of thrombotic episodes.Test results on DNA extracted from peripheral blood leukocytes need to be interpreted with caution in the setting of liver transplantation or hematopoetic stem cell transplantation (HSCT).Diagnosis of prothrombin-related thrombophilia in the setting of liver transplantation requires molecular genetic testing of donor liver, the site of prothrombin synthesis .Diagnosis of prothrombin-related thrombophilia in HSCT recipients requires molecular analysis of non-hematopoietic tissue in the recipient (e.g., buccal cells).Note: Testing for the F2 20210G>A
allele is not recommended for the following:General population screeningRoutine initial testing prior to the use of estrogen-containing contraceptives, hormone replacement therapy | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. .Diagnosis of prothrombin-related thrombophilia in the setting of liver transplantation requires molecular genetic testing of donor liver, the site of prothrombin synthesis .Diagnosis of prothrombin-related thrombophilia in HSCT recipients requires molecular analysis of non-hematopoietic tissue in the recipient (e.g., buccal cells).Note: Testing for the F2 20210G>A
allele is not recommended for the following:General population screeningRoutine initial testing prior to the use of estrogen-containing contraceptives, hormone replacement therapy (HRT), or SERMsAdults with VTE occurring in the setting of major transient risk factors (e.g., surgery, trauma) Routine initial testing in adults with arterial thrombosisIndividuals with unprovoked VTE already receiving long-term anticoagulation treatmentRoutine initial testing during pregnancyRoutine testing in women with recurrent fetal loss, placental abruption, fetal growth restriction, or preeclampsia Prenatal or newborn testingNeonates and children with asymptomatic central venous catheter | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. estrogen-containing contraceptives, hormone replacement therapy (HRT), or SERMsAdults with VTE occurring in the setting of major transient risk factors (e.g., surgery, trauma) Routine initial testing in adults with arterial thrombosisIndividuals with unprovoked VTE already receiving long-term anticoagulation treatmentRoutine initial testing during pregnancyRoutine testing in women with recurrent fetal loss, placental abruption, fetal growth restriction, or preeclampsia Prenatal or newborn testingNeonates and children with asymptomatic central venous catheter-related thrombosisRoutine testing in asymptomatic childrenRoutine testing of unselected children with a first episode of VTE Clinical CharacteristicsClinical DescriptionThe clinical expression of prothrombin-related thrombophilia is variable. Many individuals who are heterozygous or homozygous for the F2
20210G>A allele never develop thrombosis. While most individuals with prothrombin-related thrombophilia do not experience a first thrombotic event until adulthood, some have recurrent VTE before age 30 years.Venous Thromboembolism (VTE | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. onates and children with asymptomatic central venous catheter-related thrombosisRoutine testing in asymptomatic childrenRoutine testing of unselected children with a first episode of VTE Clinical CharacteristicsClinical DescriptionThe clinical expression of prothrombin-related thrombophilia is variable. Many individuals who are heterozygous or homozygous for the F2
20210G>A allele never develop thrombosis. While most individuals with prothrombin-related thrombophilia do not experience a first thrombotic event until adulthood, some have recurrent VTE before age 30 years.Venous Thromboembolism (VTE)The primary clinical manifestation of prothrombin-related thrombophilia is venous thromboembolism (VTE). Deep-vein thrombosis (DVT) and pulmonary embolism (PE) are the most common VTE. The most common site for deep-vein thrombosis is the legs, but upper-extremity thrombosis also occurs.Risk for VTE in adults heterozygous for the F2 20210G>A alleleThe relative risk for VTE is increased two- to fivefold in 20210G> | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. age 30 years.Venous Thromboembolism (VTE)The primary clinical manifestation of prothrombin-related thrombophilia is venous thromboembolism (VTE). Deep-vein thrombosis (DVT) and pulmonary embolism (PE) are the most common VTE. The most common site for deep-vein thrombosis is the legs, but upper-extremity thrombosis also occurs.Risk for VTE in adults heterozygous for the F2 20210G>A alleleThe relative risk for VTE is increased two- to fivefold in 20210G>A heterozygotes . In a large meta-analysis of 79 studies, 20210G>A heterozygosity was associated with a threefold increased risk for VTE .Among individuals with DVT, 20210G>A heterozygotes had a significantly higher rate of PE (32%) than those with the factor V Leiden allele (19%) or without thrombophilia (17%). 20210G>A heterozygotes are also at increased risk of | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. to fivefold in 20210G>A heterozygotes . In a large meta-analysis of 79 studies, 20210G>A heterozygosity was associated with a threefold increased risk for VTE .Among individuals with DVT, 20210G>A heterozygotes had a significantly higher rate of PE (32%) than those with the factor V Leiden allele (19%) or without thrombophilia (17%). 20210G>A heterozygotes are also at increased risk of developing isolated pulmonary emboli and may develop VTE at a younger age than individuals without the allele .Upper-extremity thrombosis. The available evidence suggests that heterozygosity for 20210G>A is an independent risk factor for upper-extremity thrombosis :The 20210G>A allele was reported in 5%-12% of persons with upper-extremity thrombosis not related to a central venous catheter, suggesting that the allele confers a three- to sixfold increased | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. A heterozygotes are also at increased risk of developing isolated pulmonary emboli and may develop VTE at a younger age than individuals without the allele .Upper-extremity thrombosis. The available evidence suggests that heterozygosity for 20210G>A is an independent risk factor for upper-extremity thrombosis :The 20210G>A allele was reported in 5%-12% of persons with upper-extremity thrombosis not related to a central venous catheter, suggesting that the allele confers a three- to sixfold increased risk for thrombosis in this location . The prevalence of the allele is higher in those with idiopathic (unprovoked) upper-extremity thrombosis than in those with thrombosis related to a central venous catheter .Heterozygosity for 20210G>A was associated with a fivefold increased risk for idiopathic (unprovoked) upper-extremity thrombosis (not related to malignancy or a central venous catheter) . Women heterozygous for 20210G>A who were | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. confers a three- to sixfold increased risk for thrombosis in this location . The prevalence of the allele is higher in those with idiopathic (unprovoked) upper-extremity thrombosis than in those with thrombosis related to a central venous catheter .Heterozygosity for 20210G>A was associated with a fivefold increased risk for idiopathic (unprovoked) upper-extremity thrombosis (not related to malignancy or a central venous catheter) . Women heterozygous for 20210G>A who were using oral contraceptives had a nine- to 14-fold increased risk for idiopathic upper-extremity thrombosis .Cerebral vein thrombosis20210G>A heterozygosity is associated with a six- to tenfold increased risk for cerebral vein thrombosis .In two case-control studies, women heterozygous for 20210G>A who used oral contraceptives had an 80-fold and 150-fold increased relative risk for cerebral vein thrombosis, respectively .Hepatic thrombosis and portal | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. 10G>A who were using oral contraceptives had a nine- to 14-fold increased risk for idiopathic upper-extremity thrombosis .Cerebral vein thrombosis20210G>A heterozygosity is associated with a six- to tenfold increased risk for cerebral vein thrombosis .In two case-control studies, women heterozygous for 20210G>A who used oral contraceptives had an 80-fold and 150-fold increased relative risk for cerebral vein thrombosis, respectively .Hepatic thrombosis and portal vein thrombosis are other reported complications in adult 20210G>A heterozygotes . A meta-analysis concluded that 20210G>A heterozygosity was associated with a fourfold increased risk for both idiopathic and liver disease-associated portal vein thrombosis .Thrombosis in unusual locations in adults who are heterozygous for 20210G>A also occurs more frequently than in the general population. However, these events are much less common than DVT or pulmonary emboli, and | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. thrombosis, respectively .Hepatic thrombosis and portal vein thrombosis are other reported complications in adult 20210G>A heterozygotes . A meta-analysis concluded that 20210G>A heterozygosity was associated with a fourfold increased risk for both idiopathic and liver disease-associated portal vein thrombosis .Thrombosis in unusual locations in adults who are heterozygous for 20210G>A also occurs more frequently than in the general population. However, these events are much less common than DVT or pulmonary emboli, and there is no evidence that identification of a 20210G>A allele should alter management .Retinal vein thrombosis and other ocular thrombotic events are reported in 20210G>A heterozygotes , although the association is much weaker than with DVT and/or PE .The risk for superficial venous thrombosis was increased nearly fourfold in 20210G>A heterozygotes in one study .Risk for VTE in family members of probands with the F2 20210G& | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. common than DVT or pulmonary emboli, and there is no evidence that identification of a 20210G>A allele should alter management .Retinal vein thrombosis and other ocular thrombotic events are reported in 20210G>A heterozygotes , although the association is much weaker than with DVT and/or PE .The risk for superficial venous thrombosis was increased nearly fourfold in 20210G>A heterozygotes in one study .Risk for VTE in family members of probands with the F2 20210G>A alleleWhereas the relative risk for a first episode of VTE in asymptomatic family members with a 20210G>A allele is increased two- to fivefold, the absolute risk is low. In several retrospective family studies the absolute incidence of a first VTE was 0.19%/year to 0.41%/year in asymptomatic 20210G>A heterozygotes, compared to 0.05%/year to 0.18 | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. probands with the F2 20210G>A alleleWhereas the relative risk for a first episode of VTE in asymptomatic family members with a 20210G>A allele is increased two- to fivefold, the absolute risk is low. In several retrospective family studies the absolute incidence of a first VTE was 0.19%/year to 0.41%/year in asymptomatic 20210G>A heterozygotes, compared to 0.05%/year to 0.18%/year in relatives without the allele .A prospective study of asymptomatic relatives of probands with a 20210G>A allele and arterial or venous thromboembolism found similar annual incidences of a first VTE in relatives with (0.37%/year) and without (0.12%/year) the allele .A large study of family members of probands with thrombophilia found no increased risk of VTE among relatives heterozygous for 20210G>A | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. 05%/year to 0.18%/year in relatives without the allele .A prospective study of asymptomatic relatives of probands with a 20210G>A allele and arterial or venous thromboembolism found similar annual incidences of a first VTE in relatives with (0.37%/year) and without (0.12%/year) the allele .A large study of family members of probands with thrombophilia found no increased risk of VTE among relatives heterozygous for 20210G>A .The risk for VTE is higher in asymptomatic 20210G>A heterozygotes from families with a strong history of VTE than in unselected individuals identified by population screening . The increased susceptibility to VTE in thrombosis-prone families results from the coinheritance of other unidentified inherited thrombophilic disorders.In a single large retrospective family study, the annual incidence of a first VTE was 1.10%/year in relatives homozygous for 20210G>A . | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. for 20210G>A .The risk for VTE is higher in asymptomatic 20210G>A heterozygotes from families with a strong history of VTE than in unselected individuals identified by population screening . The increased susceptibility to VTE in thrombosis-prone families results from the coinheritance of other unidentified inherited thrombophilic disorders.In a single large retrospective family study, the annual incidence of a first VTE was 1.10%/year in relatives homozygous for 20210G>A . In contrast, no VTE events occurred in the small number of homozygous family members included in two other studies . Relatives heterozygous for 20210G>A in combination with other inherited thrombophilic disorders had an annual incidence of first VTEof 0.45%-0.59%/year .Risk for VTE in children heterozygous for the F2 20210G>A alleleA combination of risk factors appears to be necessary to provoke thrombosis in children . VTE | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. 20210G>A . In contrast, no VTE events occurred in the small number of homozygous family members included in two other studies . Relatives heterozygous for 20210G>A in combination with other inherited thrombophilic disorders had an annual incidence of first VTEof 0.45%-0.59%/year .Risk for VTE in children heterozygous for the F2 20210G>A alleleA combination of risk factors appears to be necessary to provoke thrombosis in children . VTE in children is usually a complication of one or more medical conditions and/or a central venous catheter. The majority of children reported with VTE had other coexisting inherited and/or circumstantial risk factors . An increased prevalence of 20210G>A was found in neonates and children with VTE in some but not all studies. The variation in reported prevalence of the allele likely reflects differences in study design and clinical characteristics of the children included.The available data summarized | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. necessary to provoke thrombosis in children . VTE in children is usually a complication of one or more medical conditions and/or a central venous catheter. The majority of children reported with VTE had other coexisting inherited and/or circumstantial risk factors . An increased prevalence of 20210G>A was found in neonates and children with VTE in some but not all studies. The variation in reported prevalence of the allele likely reflects differences in study design and clinical characteristics of the children included.The available data summarized below suggest that asymptomatic healthy children who are heterozygotes or homozygotes for 20210G>A are at low risk for thrombosis except in the setting of strong circumstantial risk factors .Studies that support an association of 20210G>A heterozygosity with VTE in children:Several retrospective case-control studies found a heterozygous 20210G>A allele in 4%-8% of children with a first VTE compared to 1%-3% | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. the children included.The available data summarized below suggest that asymptomatic healthy children who are heterozygotes or homozygotes for 20210G>A are at low risk for thrombosis except in the setting of strong circumstantial risk factors .Studies that support an association of 20210G>A heterozygosity with VTE in children:Several retrospective case-control studies found a heterozygous 20210G>A allele in 4%-8% of children with a first VTE compared to 1%-3% of controls, suggesting a three- to fourfold increase in relative risk .In a retrospective review of 38 symptomatic children heterozygous for the 20210G>A allele, additional circumstantial risk factors were present at the time in 92% of VTE events. Central venous catheters and malignancy were among the most common risk factors identified .A meta-analysis found that 20210G>A heterozygosity was associated with a two- to threefold increased risk for a | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. VTE compared to 1%-3% of controls, suggesting a three- to fourfold increase in relative risk .In a retrospective review of 38 symptomatic children heterozygous for the 20210G>A allele, additional circumstantial risk factors were present at the time in 92% of VTE events. Central venous catheters and malignancy were among the most common risk factors identified .A meta-analysis found that 20210G>A heterozygosity was associated with a two- to threefold increased risk for a first VTE in children. The risk was increased more than ninefold in children with two or more inherited thrombophilic disorders . Other studies also found a higher risk in children doubly heterozygous for the 20210G>A and factor V Leiden alleles or with the 20210G>A allele in combination with other inherited thrombophilic disorders .Studies that do not support an association of 20210G>A heterozygosity with VTE in children:Several | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. two- to threefold increased risk for a first VTE in children. The risk was increased more than ninefold in children with two or more inherited thrombophilic disorders . Other studies also found a higher risk in children doubly heterozygous for the 20210G>A and factor V Leiden alleles or with the 20210G>A allele in combination with other inherited thrombophilic disorders .Studies that do not support an association of 20210G>A heterozygosity with VTE in children:Several studies of unselected children with a history of VTE found a low prevalence of 20210G>A heterozygosity, similar to that in controls or in the general population .In a prospective study of family members of symptomatic probands, asymptomatic children heterozygous or homozygous for 20210G>A had no thrombotic complications during an average follow-up period of five years .Cerebral vein thrombosis in children. Although some evidence suggests that 20210G>A heterozygosity | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. A heterozygosity with VTE in children:Several studies of unselected children with a history of VTE found a low prevalence of 20210G>A heterozygosity, similar to that in controls or in the general population .In a prospective study of family members of symptomatic probands, asymptomatic children heterozygous or homozygous for 20210G>A had no thrombotic complications during an average follow-up period of five years .Cerebral vein thrombosis in children. Although some evidence suggests that 20210G>A heterozygosity may predispose to central nervous system (CNS) thrombosis in children, the evidence is conflicting.Studies that support an association of 20210G>A heterozygosity with cerebral vein thrombosis in children:The combination of an inherited or acquired thrombophilic disorder (including 20210G>A heterozygosity) and an underlying medical condition conferred a fourfold increased risk for cerebral vein thrombosis, underscoring the multifactorial etiology of this thrombotic complication .A meta-analysis found that a | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. 20210G>A heterozygosity may predispose to central nervous system (CNS) thrombosis in children, the evidence is conflicting.Studies that support an association of 20210G>A heterozygosity with cerebral vein thrombosis in children:The combination of an inherited or acquired thrombophilic disorder (including 20210G>A heterozygosity) and an underlying medical condition conferred a fourfold increased risk for cerebral vein thrombosis, underscoring the multifactorial etiology of this thrombotic complication .A meta-analysis found that a 20210G>A allele was associated with a significant twofold increased risk for the combined outcome of first cerebral vein thrombosis or acute ischemic stroke in children .Studies that do not support an association of 20210G>A heterozygosity with cerebral vein thrombosis in children:In a small case-control study, the prevalence of 20210G>A heterozygosity was similar in children with cerebral vein thrombosis (2.6%) and a group of | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. .A meta-analysis found that a 20210G>A allele was associated with a significant twofold increased risk for the combined outcome of first cerebral vein thrombosis or acute ischemic stroke in children .Studies that do not support an association of 20210G>A heterozygosity with cerebral vein thrombosis in children:In a small case-control study, the prevalence of 20210G>A heterozygosity was similar in children with cerebral vein thrombosis (2.6%) and a group of control children (3.5%) .Data from a large population-based registry suggest a low prevalence of the 20210G>A allele* among children and neonates with cerebral vein thrombosis .*Note: Throughout this GeneReview, 20210G>A without specification of homo- vs. heterozygosity indicates that the studies described did not specify zygosity.Hepatic, portal, and retinal vein thromboses in children heterozygous for the 202 | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. .6%) and a group of control children (3.5%) .Data from a large population-based registry suggest a low prevalence of the 20210G>A allele* among children and neonates with cerebral vein thrombosis .*Note: Throughout this GeneReview, 20210G>A without specification of homo- vs. heterozygosity indicates that the studies described did not specify zygosity.Hepatic, portal, and retinal vein thromboses in children heterozygous for the 20210G>A allele have also been reported.Thrombosis in unusual locations (e.g., cerebral vein and hepatic vein) in children heterozygous for 20210G>A occur less commonly than thrombosis of an extremity or pulmonary embolism.Recurrent ThrombosisRisk for recurrent thrombosis in adult 20210G>A heterozygotesSummary. Current evidence suggests that 20210G>A heterozygosity has at most a modest effect on | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. thromboses in children heterozygous for the 20210G>A allele have also been reported.Thrombosis in unusual locations (e.g., cerebral vein and hepatic vein) in children heterozygous for 20210G>A occur less commonly than thrombosis of an extremity or pulmonary embolism.Recurrent ThrombosisRisk for recurrent thrombosis in adult 20210G>A heterozygotesSummary. Current evidence suggests that 20210G>A heterozygosity has at most a modest effect on recurrence risk after initial treatment of a first VTE . Although the data are conflicting, the majority of more recent studies found no increase in risk. An evidence review by the EGAPP concluded that 20210G>A heterozygosity is not predictive of VTE recurrence . The clinical circumstances of the first event (provoked or unprovoked), individual characteristics such as male sex, and global hemostasis tests (e.g. D-dimer) are more important determinants | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. heterozygosity has at most a modest effect on recurrence risk after initial treatment of a first VTE . Although the data are conflicting, the majority of more recent studies found no increase in risk. An evidence review by the EGAPP concluded that 20210G>A heterozygosity is not predictive of VTE recurrence . The clinical circumstances of the first event (provoked or unprovoked), individual characteristics such as male sex, and global hemostasis tests (e.g. D-dimer) are more important determinants of recurrence. A case-control study found that testing individuals with a first VTE for thrombophilia did not reduce the incidence of recurrence . There are no randomized or controlled trials assessing the effect of thrombophilia testing on VTE recurrence risk .Studies that support an association of 20210G>A heterozygosity and increased risk for recurrent VTE in adults:In a prospective long-term follow-up study of persons who stopped anticoagulation after treatment for a first VTE, a | [
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