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Clinical Phenotype and Bone Biopsy Characteristics in a Child with Proteus Syndrome
Proteus syndrome is a rare genetic disorder, which is characterized by progressive, segmental, or patchy overgrowth of diverse tissues of all germ layers, including the skeleton. Here, we present a 9-year-old girl with a somatic-activating mutation (c.49G > A; p.Glu17Lys) in AKT1 gene in a mosaic...
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Published in: | Calcified tissue international 2021-11, Vol.109 (5), p.586-595 |
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description | Proteus syndrome is a rare genetic disorder, which is characterized by progressive, segmental, or patchy overgrowth of diverse tissues of all germ layers, including the skeleton. Here, we present a 9-year-old girl with a somatic-activating mutation (c.49G > A; p.Glu17Lys) in
AKT1
gene in a mosaic status typical for Proteus syndrome. She presented with hemihypertrophy of the right lower limb and a “moccasin” lesion among others. A transiliac bone biopsy was analyzed for bone histology/histomorphometry as well as bone mineralization density distribution (BMDD) and osteocyte lacunae sections (OLS) characteristics based on quantitative backscattered electron imaging. Bone histomorphometry revealed highly increased mineralizing surface (Z-score + 2.3) and mineral apposition rate (Z-score + 19.3), no osteoclasts (Z-score − 2.1), and an increased amount of primary bone in the external cortex. BMDD abnormalities included a decreased mode calcium concentration in cancellous bone (Z-score − 1.7) and an increased percentage of highly mineralized cortical bone area (Z-score + 2.4) compared to reference. OLS characteristics showed several differences compared to reference data; among them, there were the highly increased OLS-porosity, OLS-area, and OLS-perimeter on the external cortex (Z-scores + 6.8, + 4.4 and 5.4, respectively). Our findings suggest that increased bone formation reduced matrix mineralization in cancellous bone while the enhanced amount of primary bone in the external cortex increased the portion of highly mineralized cortical bone and caused OLS-characteristics abnormalities. Our results indicate further that remodeling of primary bone might be disturbed or delayed in agreement with the decreased number of osteoclasts observed in this child with Proteus syndrome. |
doi_str_mv | 10.1007/s00223-021-00862-z |
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AKT1
gene in a mosaic status typical for Proteus syndrome. She presented with hemihypertrophy of the right lower limb and a “moccasin” lesion among others. A transiliac bone biopsy was analyzed for bone histology/histomorphometry as well as bone mineralization density distribution (BMDD) and osteocyte lacunae sections (OLS) characteristics based on quantitative backscattered electron imaging. Bone histomorphometry revealed highly increased mineralizing surface (Z-score + 2.3) and mineral apposition rate (Z-score + 19.3), no osteoclasts (Z-score − 2.1), and an increased amount of primary bone in the external cortex. BMDD abnormalities included a decreased mode calcium concentration in cancellous bone (Z-score − 1.7) and an increased percentage of highly mineralized cortical bone area (Z-score + 2.4) compared to reference. OLS characteristics showed several differences compared to reference data; among them, there were the highly increased OLS-porosity, OLS-area, and OLS-perimeter on the external cortex (Z-scores + 6.8, + 4.4 and 5.4, respectively). Our findings suggest that increased bone formation reduced matrix mineralization in cancellous bone while the enhanced amount of primary bone in the external cortex increased the portion of highly mineralized cortical bone and caused OLS-characteristics abnormalities. Our results indicate further that remodeling of primary bone might be disturbed or delayed in agreement with the decreased number of osteoclasts observed in this child with Proteus syndrome.</description><identifier>ISSN: 0171-967X</identifier><identifier>EISSN: 1432-0827</identifier><identifier>DOI: 10.1007/s00223-021-00862-z</identifier><identifier>PMID: 34003338</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>AKT1 protein ; Apposition ; Biochemistry ; Biomedical and Life Sciences ; Biopsy ; Bone density ; Bone growth ; Bone histomorphometry ; Bone imaging ; Bone matrix ; Bone remodeling ; Cancellous bone ; Case Reports ; Cell Biology ; Cortical bone ; Endocrinology ; Genetic disorders ; Life Sciences ; Mineralization ; Neuroimaging ; Orthopedics ; Osteoclasts ; Osteogenesis ; Phenotypes ; Porosity ; Skeleton</subject><ispartof>Calcified tissue international, 2021-11, Vol.109 (5), p.586-595</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021</rights><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c326t-d6df4a58aeeea12cae7dfb9f89fae1a7c9971b1c5ada43cf3898a6da5c05be043</cites><orcidid>0000-0001-9923-4920</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34003338$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Al Kaissi, Ali</creatorcontrib><creatorcontrib>Misof, Barbara M.</creatorcontrib><creatorcontrib>Laccone, Franco</creatorcontrib><creatorcontrib>Blouin, Stéphane</creatorcontrib><creatorcontrib>Roschger, Paul</creatorcontrib><creatorcontrib>Kircher, Susanne G.</creatorcontrib><creatorcontrib>Shboul, Mohammad</creatorcontrib><creatorcontrib>Mindler, Gabriel T.</creatorcontrib><creatorcontrib>Girsch, Werner</creatorcontrib><creatorcontrib>Ganger, Rudolf</creatorcontrib><title>Clinical Phenotype and Bone Biopsy Characteristics in a Child with Proteus Syndrome</title><title>Calcified tissue international</title><addtitle>Calcif Tissue Int</addtitle><addtitle>Calcif Tissue Int</addtitle><description>Proteus syndrome is a rare genetic disorder, which is characterized by progressive, segmental, or patchy overgrowth of diverse tissues of all germ layers, including the skeleton. Here, we present a 9-year-old girl with a somatic-activating mutation (c.49G > A; p.Glu17Lys) in
AKT1
gene in a mosaic status typical for Proteus syndrome. She presented with hemihypertrophy of the right lower limb and a “moccasin” lesion among others. A transiliac bone biopsy was analyzed for bone histology/histomorphometry as well as bone mineralization density distribution (BMDD) and osteocyte lacunae sections (OLS) characteristics based on quantitative backscattered electron imaging. Bone histomorphometry revealed highly increased mineralizing surface (Z-score + 2.3) and mineral apposition rate (Z-score + 19.3), no osteoclasts (Z-score − 2.1), and an increased amount of primary bone in the external cortex. BMDD abnormalities included a decreased mode calcium concentration in cancellous bone (Z-score − 1.7) and an increased percentage of highly mineralized cortical bone area (Z-score + 2.4) compared to reference. OLS characteristics showed several differences compared to reference data; among them, there were the highly increased OLS-porosity, OLS-area, and OLS-perimeter on the external cortex (Z-scores + 6.8, + 4.4 and 5.4, respectively). Our findings suggest that increased bone formation reduced matrix mineralization in cancellous bone while the enhanced amount of primary bone in the external cortex increased the portion of highly mineralized cortical bone and caused OLS-characteristics abnormalities. Our results indicate further that remodeling of primary bone might be disturbed or delayed in agreement with the decreased number of osteoclasts observed in this child with Proteus syndrome.</description><subject>AKT1 protein</subject><subject>Apposition</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biopsy</subject><subject>Bone density</subject><subject>Bone growth</subject><subject>Bone histomorphometry</subject><subject>Bone imaging</subject><subject>Bone matrix</subject><subject>Bone remodeling</subject><subject>Cancellous bone</subject><subject>Case Reports</subject><subject>Cell Biology</subject><subject>Cortical bone</subject><subject>Endocrinology</subject><subject>Genetic disorders</subject><subject>Life Sciences</subject><subject>Mineralization</subject><subject>Neuroimaging</subject><subject>Orthopedics</subject><subject>Osteoclasts</subject><subject>Osteogenesis</subject><subject>Phenotypes</subject><subject>Porosity</subject><subject>Skeleton</subject><issn>0171-967X</issn><issn>1432-0827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kE2LFDEQhoO4uOPqH_AgAS9e2q0k3Un66A5-wYILq-At1CTVTpae9Jh0I7O_3uisLnjYU0HVU28VD2MvBLwRAOa8AEipGpCiAbBaNreP2Eq0SjZgpXnMViCMaHptvp2yp6XcAIhWa_2EnaoWQCllV-x6PcYUPY78aktpmg974pgCv5gS8Ys47cuBr7eY0c-UY5mjLzwmjrUZx8B_xnnLr_I001L49SGFPO3oGTsZcCz0_K6esa_v331Zf2wuP3_4tH572Xgl9dwEHYYWO4tEhEJ6JBOGTT_YfkASaHzfG7ERvsOArfKDsr1FHbDz0G0IWnXGXh9z93n6sVCZ3S4WT-OIiaalONlJa6USVlf01X_ozbTkVL-rlDG9MKCgUvJI-TyVkmlw-xx3mA9OgPut3B2Vu6rc_VHubuvSy7voZbOj8G_lr-MKqCNQ6ih9p3x_-4HYX9l-jW4</recordid><startdate>20211101</startdate><enddate>20211101</enddate><creator>Al Kaissi, Ali</creator><creator>Misof, Barbara M.</creator><creator>Laccone, Franco</creator><creator>Blouin, Stéphane</creator><creator>Roschger, Paul</creator><creator>Kircher, Susanne G.</creator><creator>Shboul, Mohammad</creator><creator>Mindler, Gabriel T.</creator><creator>Girsch, Werner</creator><creator>Ganger, Rudolf</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9923-4920</orcidid></search><sort><creationdate>20211101</creationdate><title>Clinical Phenotype and Bone Biopsy Characteristics in a Child with Proteus Syndrome</title><author>Al Kaissi, Ali ; 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Here, we present a 9-year-old girl with a somatic-activating mutation (c.49G > A; p.Glu17Lys) in
AKT1
gene in a mosaic status typical for Proteus syndrome. She presented with hemihypertrophy of the right lower limb and a “moccasin” lesion among others. A transiliac bone biopsy was analyzed for bone histology/histomorphometry as well as bone mineralization density distribution (BMDD) and osteocyte lacunae sections (OLS) characteristics based on quantitative backscattered electron imaging. Bone histomorphometry revealed highly increased mineralizing surface (Z-score + 2.3) and mineral apposition rate (Z-score + 19.3), no osteoclasts (Z-score − 2.1), and an increased amount of primary bone in the external cortex. BMDD abnormalities included a decreased mode calcium concentration in cancellous bone (Z-score − 1.7) and an increased percentage of highly mineralized cortical bone area (Z-score + 2.4) compared to reference. OLS characteristics showed several differences compared to reference data; among them, there were the highly increased OLS-porosity, OLS-area, and OLS-perimeter on the external cortex (Z-scores + 6.8, + 4.4 and 5.4, respectively). Our findings suggest that increased bone formation reduced matrix mineralization in cancellous bone while the enhanced amount of primary bone in the external cortex increased the portion of highly mineralized cortical bone and caused OLS-characteristics abnormalities. Our results indicate further that remodeling of primary bone might be disturbed or delayed in agreement with the decreased number of osteoclasts observed in this child with Proteus syndrome.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>34003338</pmid><doi>10.1007/s00223-021-00862-z</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-9923-4920</orcidid></addata></record> |
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subjects | AKT1 protein Apposition Biochemistry Biomedical and Life Sciences Biopsy Bone density Bone growth Bone histomorphometry Bone imaging Bone matrix Bone remodeling Cancellous bone Case Reports Cell Biology Cortical bone Endocrinology Genetic disorders Life Sciences Mineralization Neuroimaging Orthopedics Osteoclasts Osteogenesis Phenotypes Porosity Skeleton |
title | Clinical Phenotype and Bone Biopsy Characteristics in a Child with Proteus Syndrome |
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