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Denise Horn - One of the best experts on this subject based on the ideXlab platform.
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Primary Hypertrophic Osteoarthropathy Mimicking Juvenile Idiopathic Arthritis: A Novel SLCO2A1 Mutation and Imaging Findings.
Cytogenetic and genome research, 2019Co-Authors: Murat Torgutalp, Wenke Seifert, Denise Horn, Ceren D. Durmaz, Halil Gürhan Karabulut, Zehra Akkaya, Murat TurgayAbstract:Primary hypertrophic osteoarthropathy (PHO), also known as pachydermoperiostosis, is a rare, multisystemic, autosomal recessive condition typically presenting with Digital Clubbing, osteoarthropathy, and various skin manifestations. Radiographs show distinctive periosteal reaction and thickening along the long bones. PHO is caused by homozygous mutations in the HPGD gene in chromosome 4q34.1 or the SLCO2A1 gene in 3q22.1q22.2. Here, we report on a 20-year-old male with enlarged and swollen joints with arthralgia, palmoplantar hyperhidrosis, and large hands and feet with marked Digital Clubbing. We also present radiographic, MRI, and ultrasonographic features of the case. These clinical and imaging findings were compatible with the diagnosis of PHO, and a novel homozygous mutation, c.576C>G, p.Ile192Met, was found in SLCO2A1.
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Mutations in the prostaglandin transporter encoding gene SLCO2A1 cause primary hypertrophic osteoarthropathy and isolated Digital Clubbing.
Human mutation, 2012Co-Authors: Wenke Seifert, Jirko Kühnisch, Beyhan Tüysüz, Christof Specker, Ad Brouwers, Denise HornAbstract:Digital Clubbing is usually secondary to different acquired diseases. Primary hypertrophic osteoarthropathy (PHO) is a rare hereditary disorder with variable Digital Clubbing as the most prominent feature, subperiosteal new bone formation, and arthropathy. Recently, mutations in the 15-hydroxy-prostaglandin dehydrogenase (15-PGDH) encoding gene HPGD were found to cause PHO. Here, we identified three unrelated families with different mutations in the prostaglandin transporter (PGT) encoding gene SLCO2A1 which presumably result in reduced metabolic clearance by 15-PGDH due to diminished cellular uptake of prostaglandin E2 (PGE2) by mutant PGT. In two consanguineous families, homozygous mutations, an intragenic deletion that results in frameshift and a missense mutation, are associated with a severe PHO phenotype. In a third family, a heterozygous carrier of a stop mutation presents with isolated Digital Clubbing. Thus, our study further supports the importance of PGE2 metabolism in the pathogenesis of Digital Clubbing and PHO. Hum Mutat 33:660–664, 2012. © 2012 Wiley Periodicals, Inc.
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HPGD mutations cause cranioosteoarthropathy but not autosomal dominant Digital Clubbing
European journal of human genetics : EJHG, 2009Co-Authors: Wenke Seifert, Julia Beninde, Katrin Hoffmann, Tom H. Lindner, Christian Bassir, Fuat Aksu, Christoph Hübner, Nienke E Verbeek, Stefan Mundlos, Denise HornAbstract:Cranio-osteoarthropathy, clinically classified as a variant of primary hypertrophic osteoarthropathy, is a very rare autosomal-recessive condition characterized by delayed closure of the cranial sutures and fontanels, Digital Clubbing, arthropathy, and periostosis. Recently, mutations in the gene HPGD, which encodes the NAD+-dependent 15-hydroxyprostaglandin dehydrogenase, were reported in four families affected with primary hypertrophic osteoarthropathy and one family with autosomal-recessive isolated nail Clubbing. We report the clinical and molecular findings in four patients from two families affected with cranio-osteoarthropathy and one family with isolated, autosomal dominant Digital Clubbing. Genome-wide homozygosity mapping identified a locus for cranio-osteoarthropathy harboring the HPGD gene in one affected family. We detected two novel homozygous mutations in HPGD in these families: a missense mutation affecting the NAD+ binding motif and a frameshift mutation. The clinical presentation in our patients was variable. Digital Clubbing and hyperhidrosis were present in all cases. Delayed closure of the cranial sutures and fontanels, periostosis, and arthropathy were not consistent clinical features. No HPGD mutation was detected in a familial case of autosomal dominant isolated Digital Clubbing. The failure to identify any mutation in a family with an autosomal dominant type of isolated Digital Clubbing suggests that HPGD is not the major gene for this condition.
Wenke Seifert - One of the best experts on this subject based on the ideXlab platform.
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Primary Hypertrophic Osteoarthropathy Mimicking Juvenile Idiopathic Arthritis: A Novel SLCO2A1 Mutation and Imaging Findings.
Cytogenetic and genome research, 2019Co-Authors: Murat Torgutalp, Wenke Seifert, Denise Horn, Ceren D. Durmaz, Halil Gürhan Karabulut, Zehra Akkaya, Murat TurgayAbstract:Primary hypertrophic osteoarthropathy (PHO), also known as pachydermoperiostosis, is a rare, multisystemic, autosomal recessive condition typically presenting with Digital Clubbing, osteoarthropathy, and various skin manifestations. Radiographs show distinctive periosteal reaction and thickening along the long bones. PHO is caused by homozygous mutations in the HPGD gene in chromosome 4q34.1 or the SLCO2A1 gene in 3q22.1q22.2. Here, we report on a 20-year-old male with enlarged and swollen joints with arthralgia, palmoplantar hyperhidrosis, and large hands and feet with marked Digital Clubbing. We also present radiographic, MRI, and ultrasonographic features of the case. These clinical and imaging findings were compatible with the diagnosis of PHO, and a novel homozygous mutation, c.576C>G, p.Ile192Met, was found in SLCO2A1.
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Mutations in the prostaglandin transporter encoding gene SLCO2A1 cause primary hypertrophic osteoarthropathy and isolated Digital Clubbing.
Human mutation, 2012Co-Authors: Wenke Seifert, Jirko Kühnisch, Beyhan Tüysüz, Christof Specker, Ad Brouwers, Denise HornAbstract:Digital Clubbing is usually secondary to different acquired diseases. Primary hypertrophic osteoarthropathy (PHO) is a rare hereditary disorder with variable Digital Clubbing as the most prominent feature, subperiosteal new bone formation, and arthropathy. Recently, mutations in the 15-hydroxy-prostaglandin dehydrogenase (15-PGDH) encoding gene HPGD were found to cause PHO. Here, we identified three unrelated families with different mutations in the prostaglandin transporter (PGT) encoding gene SLCO2A1 which presumably result in reduced metabolic clearance by 15-PGDH due to diminished cellular uptake of prostaglandin E2 (PGE2) by mutant PGT. In two consanguineous families, homozygous mutations, an intragenic deletion that results in frameshift and a missense mutation, are associated with a severe PHO phenotype. In a third family, a heterozygous carrier of a stop mutation presents with isolated Digital Clubbing. Thus, our study further supports the importance of PGE2 metabolism in the pathogenesis of Digital Clubbing and PHO. Hum Mutat 33:660–664, 2012. © 2012 Wiley Periodicals, Inc.
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HPGD mutations cause cranioosteoarthropathy but not autosomal dominant Digital Clubbing
European journal of human genetics : EJHG, 2009Co-Authors: Wenke Seifert, Julia Beninde, Katrin Hoffmann, Tom H. Lindner, Christian Bassir, Fuat Aksu, Christoph Hübner, Nienke E Verbeek, Stefan Mundlos, Denise HornAbstract:Cranio-osteoarthropathy, clinically classified as a variant of primary hypertrophic osteoarthropathy, is a very rare autosomal-recessive condition characterized by delayed closure of the cranial sutures and fontanels, Digital Clubbing, arthropathy, and periostosis. Recently, mutations in the gene HPGD, which encodes the NAD+-dependent 15-hydroxyprostaglandin dehydrogenase, were reported in four families affected with primary hypertrophic osteoarthropathy and one family with autosomal-recessive isolated nail Clubbing. We report the clinical and molecular findings in four patients from two families affected with cranio-osteoarthropathy and one family with isolated, autosomal dominant Digital Clubbing. Genome-wide homozygosity mapping identified a locus for cranio-osteoarthropathy harboring the HPGD gene in one affected family. We detected two novel homozygous mutations in HPGD in these families: a missense mutation affecting the NAD+ binding motif and a frameshift mutation. The clinical presentation in our patients was variable. Digital Clubbing and hyperhidrosis were present in all cases. Delayed closure of the cranial sutures and fontanels, periostosis, and arthropathy were not consistent clinical features. No HPGD mutation was detected in a familial case of autosomal dominant isolated Digital Clubbing. The failure to identify any mutation in a family with an autosomal dominant type of isolated Digital Clubbing suggests that HPGD is not the major gene for this condition.
A. Alnajjar - One of the best experts on this subject based on the ideXlab platform.
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THU0588 TAKAYASU’S ARTERITIS PRESENTING WITH UNILATERAL Digital Clubbing IN A 23 YEAR-OLD MALE
Annals of the Rheumatic Diseases, 2020Co-Authors: A. Alnajjar, A. Hegazy, N. Al GhanimAbstract:Background: Takayasu Arteritis is a chronic, large vessel arteritis that commonly involves the aorta and its major branches, mostly the ascending/descending aorta, subclavian arteries, and carotids [1]. Herein, we report a case of a 23 year-old medically free Indian male who presented to our hospital in acute distress complaining of cough, hemoptysis and shortness of breath for one week as well as intermittent fever and fatigue for five months. He presented with a BP of 140/100 mmHg as well was both systolic and early diastolic murmurs in the mitral and aortic areas, respectively. He also had a paraumbilical bruit and unilateral Clubbing in the left hand with Digital ischemia of the left index finger. Doppler ultrasound of the left arm showed monophasic flow pattern with low velocity in left distal radial, distal ulnar, and all Digital arteries, except the second Digital arteries; low velocity in the median artery; and no flow in the lateral artery of second digit (Figure 1). Computed tomography angiogram (CT Angio) (Figure 2) of the chest, abdomen, and pelvis showed fusiform aneurysm dilatation of the thoracic aorta extending into the right braciocephalic and subclavian arteries as well as the right common carotid artery. Unilateral Clubbing in patients with TA occurs as a result of subclavian artery stenosis that leads to tissue ischemia and hypoxia [2-4]. In turn, the bone marrow release megakaryocytes, which enter the systemic circulation when an A-V shunt exists [5]. Platelet-derived growth factor (PDGF) (release from megakaryocytes) and vascular endothelial growth factor (VEGF) levels are highly expressed in the connective tissues of nail beds, leading to its proliferation and platelets clumps‘ accumulation [6, 7]. Objectives: To report the fourth case worldwide and third case of an adult, respectively, with Takayasu’s arteritis who presents with unilateral Clubbing. Methods: Our patient was started on pulse steroid therapy of methylprednisolone 1 gram IV od for 5 days and later switched to prednisolone 20 mg po BID. He also received methotrexate 10 mg PO once weekly and rituximab 750 mg IV stat; another dose of rituximab was given two weeks later. Results: His Clubbing has significantly improved within 2 weeks of starting immunosuppressive therapy. He was discharged with follow up on methotrexate 12.5 mg PO once weekly and prednisilone 20 mg PO OD (to be tapered). Clubbing improved by a rate of 60% two weeks following discharge in two weeks. Conclusion: In all four cases of Takayasu arteries presenting with unilateral Clubbing, patients’ clinical condition including presence of Clubbing improved after initiation of immunosuppressive therapy. References: [1]Alibaz-Oner, F., Aydin, S. Z., & Direskeneli, H. (2015). Recent advances in Takayasu’s arteritis. European Journal of Rheumatology, 2(1), 24–30. [2]Kaditis AG, Nelson AM, Driscoll DJ. Takayasu\’s arteritis presenting with unilateral Digital Clubbing. J Rheumatol 1995;22:2346-8. [3]Ishikawa M, Okada J, Kondo H. Takayasu’s arteritis with transient clubbed finger. Clin Exp Rheumatol 1999;17:629-30. [4]Bivilibal M, Duru N, Dogdu G, Elevli M, Ayta S. A Takayasu’s Arteritis Case with Unilateral Digital Clubbing. Turk J Rheumatol. 2011;26(2):163–166. [5]Martinez-Lavin M. Hypertrophic osteoarthropathy. Curr Opin Rheumatol. 1997 Jan;9(1):83-6. Review. PubMed PMID: 9110140. [6]Dickinson CJ, Martin JF. Megakaryocytes and platelet clumps as the cause of finger Clubbing. Lancet 1987;2:1434-5. [7]Atkinson S, Fox SB. Vascular endothelial growth factor (VEGF)-A and platelet-derived growth factor (PDGF) play a central role in the pathogenesis of Digital Clubbing. J Pathol 2004;203:721-8. Disclosure of Interests: None declared
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thu0588 takayasu s arteritis presenting with unilateral Digital Clubbing in a 23 year old male
Annals of the Rheumatic Diseases, 2020Co-Authors: A. Alnajjar, A. Hegazy, Al N GhanimAbstract:Background: Takayasu Arteritis is a chronic, large vessel arteritis that commonly involves the aorta and its major branches, mostly the ascending/descending aorta, subclavian arteries, and carotids [1]. Herein, we report a case of a 23 year-old medically free Indian male who presented to our hospital in acute distress complaining of cough, hemoptysis and shortness of breath for one week as well as intermittent fever and fatigue for five months. He presented with a BP of 140/100 mmHg as well was both systolic and early diastolic murmurs in the mitral and aortic areas, respectively. He also had a paraumbilical bruit and unilateral Clubbing in the left hand with Digital ischemia of the left index finger. Doppler ultrasound of the left arm showed monophasic flow pattern with low velocity in left distal radial, distal ulnar, and all Digital arteries, except the second Digital arteries; low velocity in the median artery; and no flow in the lateral artery of second digit (Figure 1). Computed tomography angiogram (CT Angio) (Figure 2) of the chest, abdomen, and pelvis showed fusiform aneurysm dilatation of the thoracic aorta extending into the right braciocephalic and subclavian arteries as well as the right common carotid artery. Unilateral Clubbing in patients with TA occurs as a result of subclavian artery stenosis that leads to tissue ischemia and hypoxia [2-4]. In turn, the bone marrow release megakaryocytes, which enter the systemic circulation when an A-V shunt exists [5]. Platelet-derived growth factor (PDGF) (release from megakaryocytes) and vascular endothelial growth factor (VEGF) levels are highly expressed in the connective tissues of nail beds, leading to its proliferation and platelets clumps‘ accumulation [6, 7]. Objectives: To report the fourth case worldwide and third case of an adult, respectively, with Takayasu’s arteritis who presents with unilateral Clubbing. Methods: Our patient was started on pulse steroid therapy of methylprednisolone 1 gram IV od for 5 days and later switched to prednisolone 20 mg po BID. He also received methotrexate 10 mg PO once weekly and rituximab 750 mg IV stat; another dose of rituximab was given two weeks later. Results: His Clubbing has significantly improved within 2 weeks of starting immunosuppressive therapy. He was discharged with follow up on methotrexate 12.5 mg PO once weekly and prednisilone 20 mg PO OD (to be tapered). Clubbing improved by a rate of 60% two weeks following discharge in two weeks. Conclusion: In all four cases of Takayasu arteries presenting with unilateral Clubbing, patients’ clinical condition including presence of Clubbing improved after initiation of immunosuppressive therapy. References: [1]Alibaz-Oner, F., Aydin, S. Z., & Direskeneli, H. (2015). Recent advances in Takayasu’s arteritis. European Journal of Rheumatology, 2(1), 24–30. [2]Kaditis AG, Nelson AM, Driscoll DJ. Takayasu\’s arteritis presenting with unilateral Digital Clubbing. J Rheumatol 1995;22:2346-8. [3]Ishikawa M, Okada J, Kondo H. Takayasu’s arteritis with transient clubbed finger. Clin Exp Rheumatol 1999;17:629-30. [4]Bivilibal M, Duru N, Dogdu G, Elevli M, Ayta S. A Takayasu’s Arteritis Case with Unilateral Digital Clubbing. Turk J Rheumatol. 2011;26(2):163–166. [5]Martinez-Lavin M. Hypertrophic osteoarthropathy. Curr Opin Rheumatol. 1997 Jan;9(1):83-6. Review. PubMed PMID: 9110140. [6]Dickinson CJ, Martin JF. Megakaryocytes and platelet clumps as the cause of finger Clubbing. Lancet 1987;2:1434-5. [7]Atkinson S, Fox SB. Vascular endothelial growth factor (VEGF)-A and platelet-derived growth factor (PDGF) play a central role in the pathogenesis of Digital Clubbing. J Pathol 2004;203:721-8. Disclosure of Interests: None declared
N. Al Ghanim - One of the best experts on this subject based on the ideXlab platform.
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THU0588 TAKAYASU’S ARTERITIS PRESENTING WITH UNILATERAL Digital Clubbing IN A 23 YEAR-OLD MALE
Annals of the Rheumatic Diseases, 2020Co-Authors: A. Alnajjar, A. Hegazy, N. Al GhanimAbstract:Background: Takayasu Arteritis is a chronic, large vessel arteritis that commonly involves the aorta and its major branches, mostly the ascending/descending aorta, subclavian arteries, and carotids [1]. Herein, we report a case of a 23 year-old medically free Indian male who presented to our hospital in acute distress complaining of cough, hemoptysis and shortness of breath for one week as well as intermittent fever and fatigue for five months. He presented with a BP of 140/100 mmHg as well was both systolic and early diastolic murmurs in the mitral and aortic areas, respectively. He also had a paraumbilical bruit and unilateral Clubbing in the left hand with Digital ischemia of the left index finger. Doppler ultrasound of the left arm showed monophasic flow pattern with low velocity in left distal radial, distal ulnar, and all Digital arteries, except the second Digital arteries; low velocity in the median artery; and no flow in the lateral artery of second digit (Figure 1). Computed tomography angiogram (CT Angio) (Figure 2) of the chest, abdomen, and pelvis showed fusiform aneurysm dilatation of the thoracic aorta extending into the right braciocephalic and subclavian arteries as well as the right common carotid artery. Unilateral Clubbing in patients with TA occurs as a result of subclavian artery stenosis that leads to tissue ischemia and hypoxia [2-4]. In turn, the bone marrow release megakaryocytes, which enter the systemic circulation when an A-V shunt exists [5]. Platelet-derived growth factor (PDGF) (release from megakaryocytes) and vascular endothelial growth factor (VEGF) levels are highly expressed in the connective tissues of nail beds, leading to its proliferation and platelets clumps‘ accumulation [6, 7]. Objectives: To report the fourth case worldwide and third case of an adult, respectively, with Takayasu’s arteritis who presents with unilateral Clubbing. Methods: Our patient was started on pulse steroid therapy of methylprednisolone 1 gram IV od for 5 days and later switched to prednisolone 20 mg po BID. He also received methotrexate 10 mg PO once weekly and rituximab 750 mg IV stat; another dose of rituximab was given two weeks later. Results: His Clubbing has significantly improved within 2 weeks of starting immunosuppressive therapy. He was discharged with follow up on methotrexate 12.5 mg PO once weekly and prednisilone 20 mg PO OD (to be tapered). Clubbing improved by a rate of 60% two weeks following discharge in two weeks. Conclusion: In all four cases of Takayasu arteries presenting with unilateral Clubbing, patients’ clinical condition including presence of Clubbing improved after initiation of immunosuppressive therapy. References: [1]Alibaz-Oner, F., Aydin, S. Z., & Direskeneli, H. (2015). Recent advances in Takayasu’s arteritis. European Journal of Rheumatology, 2(1), 24–30. [2]Kaditis AG, Nelson AM, Driscoll DJ. Takayasu\’s arteritis presenting with unilateral Digital Clubbing. J Rheumatol 1995;22:2346-8. [3]Ishikawa M, Okada J, Kondo H. Takayasu’s arteritis with transient clubbed finger. Clin Exp Rheumatol 1999;17:629-30. [4]Bivilibal M, Duru N, Dogdu G, Elevli M, Ayta S. A Takayasu’s Arteritis Case with Unilateral Digital Clubbing. Turk J Rheumatol. 2011;26(2):163–166. [5]Martinez-Lavin M. Hypertrophic osteoarthropathy. Curr Opin Rheumatol. 1997 Jan;9(1):83-6. Review. PubMed PMID: 9110140. [6]Dickinson CJ, Martin JF. Megakaryocytes and platelet clumps as the cause of finger Clubbing. Lancet 1987;2:1434-5. [7]Atkinson S, Fox SB. Vascular endothelial growth factor (VEGF)-A and platelet-derived growth factor (PDGF) play a central role in the pathogenesis of Digital Clubbing. J Pathol 2004;203:721-8. Disclosure of Interests: None declared
Al N Ghanim - One of the best experts on this subject based on the ideXlab platform.
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thu0588 takayasu s arteritis presenting with unilateral Digital Clubbing in a 23 year old male
Annals of the Rheumatic Diseases, 2020Co-Authors: A. Alnajjar, A. Hegazy, Al N GhanimAbstract:Background: Takayasu Arteritis is a chronic, large vessel arteritis that commonly involves the aorta and its major branches, mostly the ascending/descending aorta, subclavian arteries, and carotids [1]. Herein, we report a case of a 23 year-old medically free Indian male who presented to our hospital in acute distress complaining of cough, hemoptysis and shortness of breath for one week as well as intermittent fever and fatigue for five months. He presented with a BP of 140/100 mmHg as well was both systolic and early diastolic murmurs in the mitral and aortic areas, respectively. He also had a paraumbilical bruit and unilateral Clubbing in the left hand with Digital ischemia of the left index finger. Doppler ultrasound of the left arm showed monophasic flow pattern with low velocity in left distal radial, distal ulnar, and all Digital arteries, except the second Digital arteries; low velocity in the median artery; and no flow in the lateral artery of second digit (Figure 1). Computed tomography angiogram (CT Angio) (Figure 2) of the chest, abdomen, and pelvis showed fusiform aneurysm dilatation of the thoracic aorta extending into the right braciocephalic and subclavian arteries as well as the right common carotid artery. Unilateral Clubbing in patients with TA occurs as a result of subclavian artery stenosis that leads to tissue ischemia and hypoxia [2-4]. In turn, the bone marrow release megakaryocytes, which enter the systemic circulation when an A-V shunt exists [5]. Platelet-derived growth factor (PDGF) (release from megakaryocytes) and vascular endothelial growth factor (VEGF) levels are highly expressed in the connective tissues of nail beds, leading to its proliferation and platelets clumps‘ accumulation [6, 7]. Objectives: To report the fourth case worldwide and third case of an adult, respectively, with Takayasu’s arteritis who presents with unilateral Clubbing. Methods: Our patient was started on pulse steroid therapy of methylprednisolone 1 gram IV od for 5 days and later switched to prednisolone 20 mg po BID. He also received methotrexate 10 mg PO once weekly and rituximab 750 mg IV stat; another dose of rituximab was given two weeks later. Results: His Clubbing has significantly improved within 2 weeks of starting immunosuppressive therapy. He was discharged with follow up on methotrexate 12.5 mg PO once weekly and prednisilone 20 mg PO OD (to be tapered). Clubbing improved by a rate of 60% two weeks following discharge in two weeks. Conclusion: In all four cases of Takayasu arteries presenting with unilateral Clubbing, patients’ clinical condition including presence of Clubbing improved after initiation of immunosuppressive therapy. References: [1]Alibaz-Oner, F., Aydin, S. Z., & Direskeneli, H. (2015). Recent advances in Takayasu’s arteritis. European Journal of Rheumatology, 2(1), 24–30. [2]Kaditis AG, Nelson AM, Driscoll DJ. Takayasu\’s arteritis presenting with unilateral Digital Clubbing. J Rheumatol 1995;22:2346-8. [3]Ishikawa M, Okada J, Kondo H. Takayasu’s arteritis with transient clubbed finger. Clin Exp Rheumatol 1999;17:629-30. [4]Bivilibal M, Duru N, Dogdu G, Elevli M, Ayta S. A Takayasu’s Arteritis Case with Unilateral Digital Clubbing. Turk J Rheumatol. 2011;26(2):163–166. [5]Martinez-Lavin M. Hypertrophic osteoarthropathy. Curr Opin Rheumatol. 1997 Jan;9(1):83-6. Review. PubMed PMID: 9110140. [6]Dickinson CJ, Martin JF. Megakaryocytes and platelet clumps as the cause of finger Clubbing. Lancet 1987;2:1434-5. [7]Atkinson S, Fox SB. Vascular endothelial growth factor (VEGF)-A and platelet-derived growth factor (PDGF) play a central role in the pathogenesis of Digital Clubbing. J Pathol 2004;203:721-8. Disclosure of Interests: None declared