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Thomas W. Glover - One of the best experts on this subject based on the ideXlab platform.
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microcephaly intellectual impairment bilateral vesicoureteral reflux distichiasis and glomuvenous malformations associated with a 16q24 3 contiguous gene deletion and a glomulin mutation
American Journal of Medical Genetics Part A, 2012Co-Authors: Matthew G Butler, Susan L Dagenais, Jose L Garciaperez, Pascal Brouillard, Peter J Strouse, Jeffrey W. Innis, Miikka Vikkula, Thomas W. GloverAbstract:Two hereditary syndromes, Lymphedema-distichiasis (LD) syndrome and blepharo-chelio-dontic (BCD) syndrome include the aberrant growth of eyelashes from the meibomian glands, known as distichiasis. LD is an autosomal dominant syndrome primarily characterized by distichiasis and the onset of Lymphedema usually during puberty. Mutations in the forkhead transcription factor FOXC2 are the only known cause of LD. BCD syndrome consists of autosomal dominant abnormalities of the eyelid, lip, and teeth, and the etiology remains unknown. In this report, we describe a proband that presented with distichiasis, microcephaly, bilateral grade IV vesicoureteral reflux requiring ureteral re-implantation, mild intellectual impairment and apparent glomuvenous malformations (GVM). distichiasis was present in three generations of the proband's maternal side of the family. The GVMs were severe in the proband, and maternal family members exhibited lower extremity varicosities of variable degree. A GLMN (glomulin) gene mutation was identified in the proband that accounts for the observed GVMs; no other family member could be tested. TIE2 sequencing revealed no mutations. In the proband, an additional submicroscopic 265 kb contiguous gene deletion was identified in 16q24.3, located 609 kb distal to the FOXC2 locus, which was inherited from the proband's mother. The deletion includes the C16ORF95, FBXO31, MAP1LC3B, and ZCCHC14 loci and 115 kb of a gene desert distal to FOXC2 and FOXL1. Thus, it is likely that the microcephaly, distichiasis, vesicoureteral, and intellectual impairment in this family may be caused by the deletion of one or more of these genes and/or deletion of distant cis-regulatory elements of FOXC2 expression.
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Foxc2 is expressed in developing lymphatic vessels and other tissues associated with Lymphedema-distichiasis syndrome.
Gene expression patterns : GEP, 2004Co-Authors: Susan L Dagenais, Matthew G Butler, Rebecca L. Hartsough, Robert P. Erickson, Marlys H. Witte, Thomas W. GloverAbstract:The molecular events involved in lymphatic development are poorly understood. Hence, the genes responsible for hereditary Lymphedema are of great interest due to the potential for providing insights into the mechanisms of lymphatic development, the diagnosis, prevention and treatment of Lymphedema, and lymphangiogenesis during tumor growth. Mutations in the FOXC2 transcription factor cause a major form of hereditary Lymphedema, the Lymphedema-distichiasis syndrome. We have conducted a study of Foxc2 expression during mouse development using immunohistochemistry, and examined its expression in lymphatics compared to its paralog Foxc1 and to Vegfr-3, Prox1 and other lymphatic and blood vascular proteins. We have found that Foxc2 is expressed in lymphatic primordia, jugular lymph sacs, lymphatic collectors and capillaries, as well as in podocytes, developing eyelids and other tissues associated with abnormalities in Lymphedema-distichiasis syndrome.
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mutations in foxc2 mfh 1 a forkhead family transcription factor are responsible for the hereditary Lymphedema distichiasis syndrome
American Journal of Human Genetics, 2000Co-Authors: Jianming Fang, Susan L Dagenais, Robert P. Erickson, Martin F Arlt, Michael W Glynn, Jerome L Gorski, Laurie H Seaver, Thomas W. GloverAbstract:Lymphedema-distichiasis (LD) is an autosomal dominant disorder that classically presents as Lymphedema of the limbs, with variable age at onset, and double rows of eyelashes (distichiasis). Other complications may include cardiac defects, cleft palate, extradural cysts, and photophobia, suggesting a defect in a gene with pleiotrophic effects acting during development. We previously reported neonatal Lymphedema, similar to that in Turner syndrome, associated with a t(Y;16)(q12;q24.3) translocation. A candidate gene was not found on the Y chromosome, and we directed our efforts toward the chromosome 16 breakpoint. Subsequently, a gene for LD was mapped, by linkage studies, to a 16-cM region at 16q24.3. By FISH, we determined that the translocation breakpoint was within this critical region and further narrowed the breakpoint to a 20-kb interval. Because the translocation did not appear to interrupt a gene, we considered candidate genes in the immediate region that might be inactivated by position effect. In two additional unrelated families with LD, we identified inactivating mutations—a nonsense mutation and a frameshift mutation—in the FOXC2 (MFH-1) gene. FOXC2 is a member of the forkhead/winged-helix family of transcription factors, whose members are involved in diverse developmental pathways. FOXC2 knockout mice display cardiovascular, craniofacial, and vertebral abnormalities similar to those seen in LD syndrome. Our findings show that FOXC2 haploinsufficiency results in LD. FOXC2 represents the second known gene to result in hereditary Lymphedema, and LD is only the second hereditary disorder known to be caused by a mutation in a forkhead-family gene.
Matteo Bertelli - One of the best experts on this subject based on the ideXlab platform.
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imbalance between expression of foxc2 and its lncrna in Lymphedema distichiasis caused by frameshift mutations
Genes, 2021Co-Authors: Sara Missaglia, Paolo Enrico Maltese, Daniela Tavian, Sandro Michelini, Andrea Bonanomi, Matteo BertelliAbstract:Forkhead-box C2 (FOXC2) is a transcription factor involved in lymphatic system development. FOXC2 mutations cause Lymphedema-distichiasis syndrome (LD). Recently, a natural antisense was identified, called lncRNA FOXC2-AS1, which increases FOXC2 mRNA stability. No studies have evaluated FOXC2 and FOXC2-AS1 blood expression in LD and healthy subjects. Here, we show that FOXC2 and FOXC-AS1 expression levels were similar in both controls and patients, and a significantly higher amount of both RNAs was observed in females. A positive correlation between FOXC2 and FOXC2-AS1 expression was found in both controls and patients, excluding those with frameshift mutations. In these patients, the FOXC2-AS1/FOXC2 ratio was about 1:1, while it was higher in controls and patients carrying other types of mutations. The overexpression or silencing of FOXC2-AS1 determined a significant increase or reduction in FOXC2 wild-type and frameshift mutant proteins, respectively. Moreover, confocal and bioinformatic analysis revealed that these variations caused the formation of nuclear proteins aggregates also involving DNA. In conclusion, patients with frameshift mutations presented lower values of the FOXC2-AS1/FOXC2 ratio, due to a decrease in FOXC2-AS1 expression. The imbalance between FOXC2 mRNA and its lncRNA could represent a molecular mechanism to reduce the amount of FOXC2 misfolded proteins, protecting cells from damage.
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foxc2 disease mutations identified in Lymphedema distichiasis patients impair transcriptional activity and cell proliferation
International Journal of Molecular Sciences, 2020Co-Authors: Daniela Tavian, Paolo Enrico Maltese, Sara Missaglia, Sandro Michelini, Elena Manara, Alvaro Mordente, Matteo BertelliAbstract:FOXC2 is a member of the human forkhead-box gene family and encodes a regulatory transcription factor. Mutations in FOXC2 have been associated with Lymphedema distichiasis (LD), an autosomal dominant disorder that primarily affects the limbs. Most patients also show extra eyelashes, a condition known as distichiasis. We previously reported genetic and clinical findings in six unrelated families with LD. Half the patients showed missense mutations, two carried frameshift mutations and a stop mutation was identified in a last patient. Here we analyzed the subcellular localization and transactivation activity of the mutant proteins, showing that all but one (p.Y109*) localized to the nucleus. A significant reduction of transactivation activity was observed in four mutants (p.L80F, p.H199Pfs*264, p.I213Tfs*18, p.Y109*) compared with wild type FOXC2 protein, while only a partial loss of function was associated with p.V228M. The mutant p.I213V showed a very slight increase of transactivation activity. Finally, immunofluorescence analysis revealed that some mutants were sequestered into nuclear aggregates and caused a reduction of cell viability. This study offers new insights into the effect of FOXC2 mutations on protein function and shows the involvement of aberrant aggregation of FOXC2 proteins in cell death.
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Lymphedema distichiasis syndrome
Journal of Blood & Lymph, 2018Co-Authors: Yeltay Rakhmanov, Paolo Enrico Maltese, Stefano Paolacci, Carla Marinelli, Matteo BertelliAbstract:We reviewed the literature and disease guidelines in order to summarize the clinical utility of genetic tests for Lymphedema-distichiasis syndrome (LD). In around 75% of LD cases the phenotype is inherited in an autosomal dominant manner, in the remaining cases the onset is sporadic due to de novo germline mutations. The prevalence is unknown. Mutations in FOXC2 are associated with 95% of LD cases, therefore genetic heterogeneity may be present. Clinical diagnosis involves clinical examination targeted at identifying primary Lymphedema (chronic swelling of the extremities) and distichiasis (double row of eyelashes). The genetic test is useful for confirming the clinical diagnosis, as well as for differential diagnosis. The test also allows to establish recurrence risk within the family, and, potentially, to access clinical trials.
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foxc2 disease mutations identified in Lymphedema distichiasis patients cause both loss and gain of protein function
Oncotarget, 2016Co-Authors: Daniela Tavian, Paolo Enrico Maltese, Sara Missaglia, Sandro Michelini, Alessandro Fiorentino, M Ricci, Roberta Serrani, Michael A Walter, Matteo BertelliAbstract:// Daniela Tavian 1 , Sara Missaglia 1 , Paolo E. Maltese 2 , Sandro Michelini 3 , Alessandro Fiorentino 3 , Maurizio Ricci 4 , Roberta Serrani 4 , Michael A. Walter 5,6 and Matteo Bertelli 2 1 Laboratory of Cellular Biochemistry and Molecular Biology, CRIBENS, Catholic University of the Sacred Heart, Milan, Italy 2 MAGI Non-Profit Human Medical Genetics Institute, Rovereto (TN), Italy 3 Department of Vascular Rehabilitation, San Giovanni Battista Hospital, Rome, Italy 4 Medicina Riabilitativa, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Torrette, Italy 5 Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada 6 Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton, Alberta, Canada Correspondence to: Daniela Tavian, email: // Keywords : primary Lymphedema, distichiasis, Foxc2 gene mutations, transcription factor, gain of function, Pathology Section Received : December 21, 2015 Accepted : May 22, 2016 Published : June 02, 2016 Abstract Dominant mutations in the FOXC2 gene cause a form of Lymphedema primarily of the limbs that usually develops at or after puberty. In 90-95% of patients, Lymphedema is accompanied by distichiasis. FOXC2 is a member of the forkhead/winged-helix family of transcription factors and plays essential roles in different developmental pathways and physiological processes. We previously described six unrelated families with primary Lymphedema-distichiasis in which patients showed different FOXC2 mutations located outside of the forkhead domain. Of those, four were missense mutations, one a frameshift mutation, and the last a stop mutation. To assess their pathogenic potential, we have now examined the subcellular localization and the transactivation activity of the mutated FOXC2 proteins. All six FOXC2 mutant proteins were able to localize into the nucleus; however, the frameshift truncated protein appeared to be sequestered into nuclear aggregates. A reduction in the ability to activate FOXC1/FOXC2 response elements was detected in 50% of mutations, while the remaining ones caused an increase of protein transactivation activity. Our data reveal that either a complete loss or a significant gain of FOXC2 function can cause a perturbation of lymphatic vessel formation leading to Lymphedema.
Miikka Vikkula - One of the best experts on this subject based on the ideXlab platform.
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microcephaly intellectual impairment bilateral vesicoureteral reflux distichiasis and glomuvenous malformations associated with a 16q24 3 contiguous gene deletion and a glomulin mutation
American Journal of Medical Genetics Part A, 2012Co-Authors: Matthew G Butler, Susan L Dagenais, Jose L Garciaperez, Pascal Brouillard, Peter J Strouse, Jeffrey W. Innis, Miikka Vikkula, Thomas W. GloverAbstract:Two hereditary syndromes, Lymphedema-distichiasis (LD) syndrome and blepharo-chelio-dontic (BCD) syndrome include the aberrant growth of eyelashes from the meibomian glands, known as distichiasis. LD is an autosomal dominant syndrome primarily characterized by distichiasis and the onset of Lymphedema usually during puberty. Mutations in the forkhead transcription factor FOXC2 are the only known cause of LD. BCD syndrome consists of autosomal dominant abnormalities of the eyelid, lip, and teeth, and the etiology remains unknown. In this report, we describe a proband that presented with distichiasis, microcephaly, bilateral grade IV vesicoureteral reflux requiring ureteral re-implantation, mild intellectual impairment and apparent glomuvenous malformations (GVM). distichiasis was present in three generations of the proband's maternal side of the family. The GVMs were severe in the proband, and maternal family members exhibited lower extremity varicosities of variable degree. A GLMN (glomulin) gene mutation was identified in the proband that accounts for the observed GVMs; no other family member could be tested. TIE2 sequencing revealed no mutations. In the proband, an additional submicroscopic 265 kb contiguous gene deletion was identified in 16q24.3, located 609 kb distal to the FOXC2 locus, which was inherited from the proband's mother. The deletion includes the C16ORF95, FBXO31, MAP1LC3B, and ZCCHC14 loci and 115 kb of a gene desert distal to FOXC2 and FOXL1. Thus, it is likely that the microcephaly, distichiasis, vesicoureteral, and intellectual impairment in this family may be caused by the deletion of one or more of these genes and/or deletion of distant cis-regulatory elements of FOXC2 expression.
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Molecular Basis of Vascular Birthmarks
Seminars in Plastic Surgery, 2006Co-Authors: Ben Pocock, Laurence M. Boon, Miikka VikkulaAbstract:Vascular anomalies affect up to 10% of newborns, largely because of the high incidence of hemangioma of infancy. Vascular anomalies also frequently occur in adults; there is high prevalence of capillary malformations (0.3%). These cutaneous stains often cause psychosocial problems related to their visibility. Venous malformations occur in the skin and in internal organs and may cause destruction. Primary Lymphedema causes lifelong morbidity, and arteriovenous malformations, in addition to causing distortion, obstruction, and pain, can be life endangering. The pathophysiology of these anomalies has stayed largely unknown, but genetic studies have revealed clues to their etiology. Genetic defects cause hereditary types of venous malformation, cutaneous and mucosal (VMCM); glomuvenous malformation (GVM); primary congenital Lymphedema (Milroy disease); Lymphedema-distichiasis syndrome; hypotrichosis-Lymphedema-telangiectasia (HLT) syndrome; hereditary hemorrhagic telangiectasia (HHT); cerebral cavernous malformation (CCM); and a newly recognized disorder, capillary malformation–arteriovenous malfor- mation (CM-AVM). These seminal discoveries have not only permitted a more precise clinical classification and diagnosis (a prerequisite for corrective measures for prevention, treatment, and follow-up) but also pointed the way to the identification of factors that play an important role in vasculogenesis or angiogenesis, or both.
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mutations in the transcription factor gene sox18 underlie recessive and dominant forms of hypotrichosis Lymphedema telangiectasia
American Journal of Human Genetics, 2003Co-Authors: Alexandre Irrthum, Koenraad Devriendt, David Chitayat, Gert Matthijs, Conrad P Glade, Peter M Steijlen, J P Fryns, Maurice A M Van Steensel, Miikka VikkulaAbstract:Hereditary Lymphedema is a developmental disorder characterized by chronic swelling of the extremities due to dysfunction of the lymphatic vessels. Two responsible genes have been identified: the vascular endothelial growth factor receptor 3 (VEGFR3) gene, implicated in congenital Lymphedema, or Milroy disease, and the forkhead-related transcription factor gene FOXC2, causing Lymphedema-distichiasis. We describe three families with an unusual association of hypotrichosis, Lymphedema, and telangiectasia. Using microsatellite analysis, we first excluded both VEGFR3 and FOXC2 as causative genes; we then considered the murine ragged phenotype, caused by mutations in the Sox18 transcription factor, as a likely counterpart to the human disease, because it presents a combination of hair and cardiovascular anomalies, including symptoms of lymphatic dysfunction. Two of the families were consanguineous; in affected members of these families, we identified homozygous missense mutations in the SOX18 gene, located in 20q13. The two amino acid substitutions, W95R and A104P, affect conserved residues in the first α helix of the DNA-binding domain of the transcription factor. In the third family, the parents were nonconsanguineous, and both the affected child and his brother, who died in utero with hydrops fetalis, showed a heterozygous nonsense mutation that truncates the SOX18 protein in its transactivation domain; this substitution was not found in genomic DNA from either parent and hence constitutes a de novo germline mutation. Thus, we show that SOX18 mutations in humans cause both recessive and dominant hypotrichosis-Lymphedema-telangiectasia, suggesting that, in addition to its established role in hair and blood vessel development, the SOX18 transcription factor plays a role in the development and/or maintenance of lymphatic vessels.
Shoji Yabuki - One of the best experts on this subject based on the ideXlab platform.
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a screening method to distinguish syndromic from sporadic spinal extradural arachnoid cyst
Journal of Orthopaedic Science, 2018Co-Authors: Yoji Ogura, Shoji Yabuki, Shunsuke Fujibayashi, Eijiro Okada, Akio Iwanami, Masaya Nakamura, Kota Watanabe, Morio Matsumoto, Ken J Ishii, Shiro IkegawaAbstract:Abstract Background Spinal extradural arachnoid cyst (SEDAC) is a cystic lesion that protrudes into the epidural space from a small dural defect. Early diagnosis of SEDAC is important because its expansion causes neurological damage. Two types of SEDAC, syndromic and sporadic, are present. Syndromic SEDAC is inherited as a part of Lymphedema-distichiasis syndrome caused by mutations in the FOXC2 gene; however, it is often mistaken as sporadic because of low penetrance. It is not reasonable to conduct a genetic testing for all SEDAC patients and their family members. The aim of this study is to establish an effective screening method to distinguish syndromic SEDAC from sporadic SEDAC. Methods We performed a retrospective review of medical records and imaging studies of 29 subjects who were diagnosed with SEDAC. Clinical features, family history and magnetic resonance imaging (MRI) were analyzed. Mutations in FOXC2 were examined by Sanger-sequencing of the entire coding region of the genes. SEDAC having a mutation in FOXC2 gene was defined with syndromic SEDAC. Results Eleven subjects had a heterozygous mutation in FOXC2 . They were all familial and hence syndromic SEDAC. Only one proband had known family history of SEDAC at diagnosis. MRI findings and physical examinations, especially eye and leg examinations, were quite useful to screen syndromic SEDAC. Physical examination often showed accompanying Lymphedema and distichiasis in syndromic SEDAC. Syndromic SEDAC tended to have multiple cysts out of the thoracolumbar area. Conclusions We established an effective screening method based on physical examinations and MRI findings.
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foxc2 mutations in familial and sporadic spinal extradural arachnoid cyst
PLOS ONE, 2013Co-Authors: Yoji Ogura, Shoji Yabuki, Shinichi Kikuchi, Aritoshi Iida, Ikuyo Kou, Masahiro Nakajima, Yoshiaki Toyama, Hiroki Kano, Masaaki Shiina, Kazuhiro OgataAbstract:Spinal extradural arachnoid cyst (SEDAC) is a cyst in the spinal canal that protrudes into the epidural space from a defect in the dura mater. Most cases are sporadic; however, three familial SEDAC cases have been reported, suggesting genetic etiological factors. All familial cases are associated with Lymphedema-distichiasis syndrome (LDS), whose causal gene is FOXC2. However, FOXC2 mutation analysis has been performed in only 1 family, and no mutation analysis has been performed on sporadic (non-familial) SEDACs. We recruited 17 SEDAC subjects consisting of 2 familial and 7 sporadic cases and examined FOXC2 mutations by Sanger sequencing and structural abnormalities by TaqMan copy number assay. We identified 2 novel FOXC2 mutations in 2 familial cases. Incomplete LDS penetrance was noted in both families. Four subjects presented with SEDACs only. Thus, SEDAC caused by the heterozygous FOXC2 loss-of-function mutation should be considered a feature of LDS, although it often manifests as the sole symptom. Seven sporadic SEDAC subjects had no FOXC2 mutations, no symptoms of LDS, and showed differing clinical characteristics from those who had FOXC2 mutations, suggesting that other gene(s) besides FOXC2 are likely to be involved in SEDAC.
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spinal extradural arachnoid cysts associated with distichiasis and Lymphedema
American Journal of Medical Genetics Part A, 2007Co-Authors: Shoji Yabuki, Shinichi Kikuchi, Shiro IkegawaAbstract:Spinal extradural arachnoid cysts (SEDAC) are lesions communicating to the subarachnoid space of the spinal canal via a dural defect. SEDAC occupies intraspinal space and sometimes causes neurological disturbances. Although most reported cases are sporadic, several familial cases have been described, suggesting a genetic etiology. Here we report on a family with SEDAC inherited in an autosomal dominant mode. Detailed study showed that the family has the Lymphedema-distichiasis syndrome. Among family members examined, a total of ten in two generations manifested all or some of the following features: SEDAC, distichiasis and Lymphedema. Seven had spinal cysts, four had both SEDAC and distichiasis, and one had SEDAC distichiasis and Lymphedema; three did not have SEDAC. These findings, together with rarity of both distichiasis and Lymphedema in the general population, support that all of the ten members were affected with one clinical entity, the Lymphedema-distichiasis syndrome. The distribution of features illustrates the variable expressivity of clinical manifestations. Although FOXC2 mutation analysis was not performed in our family, it is likely that SEDAC is a component manifestation of Lymphedema-distichiasis syndrome and more consistent in our family than those reported. © 2007 Wiley-Liss, Inc.
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clinical report spinal extradural arachnoid cysts associated with distichiasis and Lymphedema
2007Co-Authors: Shoji Yabuki, Shinichi Kikuchi, Shiro IkegawaAbstract:Spinal extradural arachnoid cysts (SEDAC) are lesions communicating to the subarachnoid space of the spinal canal via a dural defect. SEDAC occupies intraspinal space and sometimes causes neurological disturbances. Although most reported cases are sporadic, several familial cases have been described, suggesting a genetic etiology. Here we report on a family with SEDAC inherited in an autosomal dominant mode. Detailed study showed that the family has the Lymphedema-distichiasis syndrome. Among family members examined, a total of ten in two generations manifested all or some of the following features: SEDAC, distichiasis and Lymphedema. Seven had spinal cysts, four had both SEDAC and distichiasis, and one had SEDAC distichiasis and Lymphedema; three did not have SEDAC. These findings, together with rarity of both distichiasis and Lymphedema in the general population, support that all of the ten members were affected with one clinical entity, the Lymphedema-distichiasis syndrome. The distribution of features illustrates the variable expressivity of clinical manifestations. Although FOXC2 mutation analysis was not performed in our family, it is likely that SEDAC is a component manifestation of Lymphedema-distichiasis syndrome and more consistent in our family than those reported. 2007 Wiley-Liss, Inc.
Shiro Ikegawa - One of the best experts on this subject based on the ideXlab platform.
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a screening method to distinguish syndromic from sporadic spinal extradural arachnoid cyst
Journal of Orthopaedic Science, 2018Co-Authors: Yoji Ogura, Shoji Yabuki, Shunsuke Fujibayashi, Eijiro Okada, Akio Iwanami, Masaya Nakamura, Kota Watanabe, Morio Matsumoto, Ken J Ishii, Shiro IkegawaAbstract:Abstract Background Spinal extradural arachnoid cyst (SEDAC) is a cystic lesion that protrudes into the epidural space from a small dural defect. Early diagnosis of SEDAC is important because its expansion causes neurological damage. Two types of SEDAC, syndromic and sporadic, are present. Syndromic SEDAC is inherited as a part of Lymphedema-distichiasis syndrome caused by mutations in the FOXC2 gene; however, it is often mistaken as sporadic because of low penetrance. It is not reasonable to conduct a genetic testing for all SEDAC patients and their family members. The aim of this study is to establish an effective screening method to distinguish syndromic SEDAC from sporadic SEDAC. Methods We performed a retrospective review of medical records and imaging studies of 29 subjects who were diagnosed with SEDAC. Clinical features, family history and magnetic resonance imaging (MRI) were analyzed. Mutations in FOXC2 were examined by Sanger-sequencing of the entire coding region of the genes. SEDAC having a mutation in FOXC2 gene was defined with syndromic SEDAC. Results Eleven subjects had a heterozygous mutation in FOXC2 . They were all familial and hence syndromic SEDAC. Only one proband had known family history of SEDAC at diagnosis. MRI findings and physical examinations, especially eye and leg examinations, were quite useful to screen syndromic SEDAC. Physical examination often showed accompanying Lymphedema and distichiasis in syndromic SEDAC. Syndromic SEDAC tended to have multiple cysts out of the thoracolumbar area. Conclusions We established an effective screening method based on physical examinations and MRI findings.
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spinal extradural arachnoid cysts associated with distichiasis and Lymphedema
American Journal of Medical Genetics Part A, 2007Co-Authors: Shoji Yabuki, Shinichi Kikuchi, Shiro IkegawaAbstract:Spinal extradural arachnoid cysts (SEDAC) are lesions communicating to the subarachnoid space of the spinal canal via a dural defect. SEDAC occupies intraspinal space and sometimes causes neurological disturbances. Although most reported cases are sporadic, several familial cases have been described, suggesting a genetic etiology. Here we report on a family with SEDAC inherited in an autosomal dominant mode. Detailed study showed that the family has the Lymphedema-distichiasis syndrome. Among family members examined, a total of ten in two generations manifested all or some of the following features: SEDAC, distichiasis and Lymphedema. Seven had spinal cysts, four had both SEDAC and distichiasis, and one had SEDAC distichiasis and Lymphedema; three did not have SEDAC. These findings, together with rarity of both distichiasis and Lymphedema in the general population, support that all of the ten members were affected with one clinical entity, the Lymphedema-distichiasis syndrome. The distribution of features illustrates the variable expressivity of clinical manifestations. Although FOXC2 mutation analysis was not performed in our family, it is likely that SEDAC is a component manifestation of Lymphedema-distichiasis syndrome and more consistent in our family than those reported. © 2007 Wiley-Liss, Inc.
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clinical report spinal extradural arachnoid cysts associated with distichiasis and Lymphedema
2007Co-Authors: Shoji Yabuki, Shinichi Kikuchi, Shiro IkegawaAbstract:Spinal extradural arachnoid cysts (SEDAC) are lesions communicating to the subarachnoid space of the spinal canal via a dural defect. SEDAC occupies intraspinal space and sometimes causes neurological disturbances. Although most reported cases are sporadic, several familial cases have been described, suggesting a genetic etiology. Here we report on a family with SEDAC inherited in an autosomal dominant mode. Detailed study showed that the family has the Lymphedema-distichiasis syndrome. Among family members examined, a total of ten in two generations manifested all or some of the following features: SEDAC, distichiasis and Lymphedema. Seven had spinal cysts, four had both SEDAC and distichiasis, and one had SEDAC distichiasis and Lymphedema; three did not have SEDAC. These findings, together with rarity of both distichiasis and Lymphedema in the general population, support that all of the ten members were affected with one clinical entity, the Lymphedema-distichiasis syndrome. The distribution of features illustrates the variable expressivity of clinical manifestations. Although FOXC2 mutation analysis was not performed in our family, it is likely that SEDAC is a component manifestation of Lymphedema-distichiasis syndrome and more consistent in our family than those reported. 2007 Wiley-Liss, Inc.
