SMAD6 Genotype Predicts Neurodevelopment in Nonsyndromic Craniosynostosis
BACKGROUND:De novo or rare transmitted mutations in the SMAD6 gene affect 7 percent of midline nonsyndromic synostosis patients. This study aimed to determine the neurocognitive sequelae of SMAD6 synostosis. METHODS:Nonsyndromic synostosis patients 6 years or older with SMAD6 mutations and non-SMAD6...
Gespeichert in:
| Veröffentlicht in: | Plastic and reconstructive surgery (1963) 2020-01, Vol.145 (1), p.117e-125e |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 125e |
|---|---|
| container_issue | 1 |
| container_start_page | 117e |
| container_title | Plastic and reconstructive surgery (1963) |
| container_volume | 145 |
| creator | Wu, Robin T. Timberlake, Andrew T. Abraham, Paul F. Gabrick, Kyle S. Lu, Xiaona Peck, Connor J. Sawh-Martinez, Rajendra F. Steinbacher, Derek M. Alperovich, Michael A. Persing, John A. |
| description | BACKGROUND:De novo or rare transmitted mutations in the SMAD6 gene affect 7 percent of midline nonsyndromic synostosis patients. This study aimed to determine the neurocognitive sequelae of SMAD6 synostosis.
METHODS:Nonsyndromic synostosis patients 6 years or older with SMAD6 mutations and non-SMAD6 nonsyndromic synostosis controls were recruited. All patients completed a double-blinded neurodevelopmental battery (i.e., Wechsler Fundamentals, Wechsler Abbreviated Scale of Intelligence, Beery-Buktenica Developmental test), and parents/guardians completed behavioral surveys (Behavior Rating Inventory of Executive Function and Behavior Rating System for Children).
RESULTS:Twenty-eight patients participated10 known SMAD6 patients (average age, 10 years; 1 female; eight metopic and two sagittal; nine treated with cranial vault remodeling and one treated with strip craniectomy) and 18 non-SMAD6 controls (age, 9.5 years; three female; 12 metopic and six sagittal; 17 treated with cranial vault remodeling and one treated with strip craniectomy). There were no differences between any demographics. Testing age, surgical age, parental education, and household income correlated with cognition (p < 0.05). After controlling for these factors, SMAD6 patients performed worse on numerical operations (p = 0.046), performance intelligence quotient (p = 0.018), full-scale intelligence quotient (p = 0.010), and motor coordination (p = 0.043) compared to age/race/gender/synostosis/operation-matched controls. On behavioral surveys, SMAD6 patients scored worse on 14 assessments, including aggression, communication, and behavior.
CONCLUSIONS:This prospective double-blinded study revealed that neuropsychiatric development of nonsyndromic synostosis may be under genetic control. SMAD6 mutations led to poorer mathematics, performance intelligence quotient, full-scale intelligence quotient, and motor coordination, even after controlling for exogenous factors. Genetic testing may be critical for advocating early adjunctive neurodevelopmental therapy.
CLINICAL QUESTION/LEVEL OF EVIDENCE:Risk, II. |
| doi_str_mv | 10.1097/PRS.0000000000006319 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2302467146</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2302467146</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4019-6491b7534dadd1264bc97c759de279cac8d56eb01f9d9a507c52c95221220cf3</originalsourceid><addsrcrecordid>eNqFkU1LxDAQhoMo7vrxD0R69FJNJkljjrLqKviF6710k1m22jY1aV323xvdVcSDBoYw8Lwz8AwhB4weM6rVycPj5Jj-eBlneoMMmQSdChCwSYaUckgZlTAgOyE8U8oUz-Q2GXAmNWhJh-R6cnt2niVjbFy3bDF58GhL04XkDnvvLL5h5doamy4pm-TONWHZWO_q0iQjXzSli70LnQtl2CNbs6IKuL_-d8nT5cXT6Cq9uR9fj85uUiMo02kmNJsqyYUtrGWQianRyiipLYLSpjCnVmY4pWymrS4kVUaC0RKAAVAz47vkaDW29e61x9DldRkMVlXRoOtDDpyCyBQTWUTFCjXeheBxlre-rAu_zBnNPxzm0WH-22GMHa439NMa7XfoS1oETlfAwlUd-vBS9Qv0-RyLqpv_N1v8Ef3EopoUKMRjxS6NxRV_B4rFjSI</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2302467146</pqid></control><display><type>article</type><title>SMAD6 Genotype Predicts Neurodevelopment in Nonsyndromic Craniosynostosis</title><source>MEDLINE</source><source>Journals@Ovid Complete</source><creator>Wu, Robin T. ; Timberlake, Andrew T. ; Abraham, Paul F. ; Gabrick, Kyle S. ; Lu, Xiaona ; Peck, Connor J. ; Sawh-Martinez, Rajendra F. ; Steinbacher, Derek M. ; Alperovich, Michael A. ; Persing, John A.</creator><creatorcontrib>Wu, Robin T. ; Timberlake, Andrew T. ; Abraham, Paul F. ; Gabrick, Kyle S. ; Lu, Xiaona ; Peck, Connor J. ; Sawh-Martinez, Rajendra F. ; Steinbacher, Derek M. ; Alperovich, Michael A. ; Persing, John A.</creatorcontrib><description>BACKGROUND:De novo or rare transmitted mutations in the SMAD6 gene affect 7 percent of midline nonsyndromic synostosis patients. This study aimed to determine the neurocognitive sequelae of SMAD6 synostosis.
METHODS:Nonsyndromic synostosis patients 6 years or older with SMAD6 mutations and non-SMAD6 nonsyndromic synostosis controls were recruited. All patients completed a double-blinded neurodevelopmental battery (i.e., Wechsler Fundamentals, Wechsler Abbreviated Scale of Intelligence, Beery-Buktenica Developmental test), and parents/guardians completed behavioral surveys (Behavior Rating Inventory of Executive Function and Behavior Rating System for Children).
RESULTS:Twenty-eight patients participated10 known SMAD6 patients (average age, 10 years; 1 female; eight metopic and two sagittal; nine treated with cranial vault remodeling and one treated with strip craniectomy) and 18 non-SMAD6 controls (age, 9.5 years; three female; 12 metopic and six sagittal; 17 treated with cranial vault remodeling and one treated with strip craniectomy). There were no differences between any demographics. Testing age, surgical age, parental education, and household income correlated with cognition (p < 0.05). After controlling for these factors, SMAD6 patients performed worse on numerical operations (p = 0.046), performance intelligence quotient (p = 0.018), full-scale intelligence quotient (p = 0.010), and motor coordination (p = 0.043) compared to age/race/gender/synostosis/operation-matched controls. On behavioral surveys, SMAD6 patients scored worse on 14 assessments, including aggression, communication, and behavior.
CONCLUSIONS:This prospective double-blinded study revealed that neuropsychiatric development of nonsyndromic synostosis may be under genetic control. SMAD6 mutations led to poorer mathematics, performance intelligence quotient, full-scale intelligence quotient, and motor coordination, even after controlling for exogenous factors. Genetic testing may be critical for advocating early adjunctive neurodevelopmental therapy.
CLINICAL QUESTION/LEVEL OF EVIDENCE:Risk, II.</description><identifier>ISSN: 0032-1052</identifier><identifier>EISSN: 1529-4242</identifier><identifier>DOI: 10.1097/PRS.0000000000006319</identifier><identifier>PMID: 31592950</identifier><language>eng</language><publisher>United States: by the American Society of Plastic Surgeons</publisher><subject>Case-Control Studies ; Child ; Child Behavior ; Child Development ; Child, Preschool ; Craniosynostoses - complications ; Craniosynostoses - genetics ; Craniosynostoses - surgery ; Craniotomy - methods ; Developmental Disabilities - diagnosis ; Developmental Disabilities - genetics ; Developmental Disabilities - prevention & control ; Double-Blind Method ; Female ; Follow-Up Studies ; Humans ; Infant ; Intelligence Tests ; Loss of Function Mutation ; Male ; Prospective Studies ; Reconstructive Surgical Procedures - methods ; Skull - surgery ; Smad6 Protein - genetics ; Treatment Outcome</subject><ispartof>Plastic and reconstructive surgery (1963), 2020-01, Vol.145 (1), p.117e-125e</ispartof><rights>by the American Society of Plastic Surgeons</rights><rights>2020American Society of Plastic Surgeons</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4019-6491b7534dadd1264bc97c759de279cac8d56eb01f9d9a507c52c95221220cf3</citedby><cites>FETCH-LOGICAL-c4019-6491b7534dadd1264bc97c759de279cac8d56eb01f9d9a507c52c95221220cf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31592950$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Robin T.</creatorcontrib><creatorcontrib>Timberlake, Andrew T.</creatorcontrib><creatorcontrib>Abraham, Paul F.</creatorcontrib><creatorcontrib>Gabrick, Kyle S.</creatorcontrib><creatorcontrib>Lu, Xiaona</creatorcontrib><creatorcontrib>Peck, Connor J.</creatorcontrib><creatorcontrib>Sawh-Martinez, Rajendra F.</creatorcontrib><creatorcontrib>Steinbacher, Derek M.</creatorcontrib><creatorcontrib>Alperovich, Michael A.</creatorcontrib><creatorcontrib>Persing, John A.</creatorcontrib><title>SMAD6 Genotype Predicts Neurodevelopment in Nonsyndromic Craniosynostosis</title><title>Plastic and reconstructive surgery (1963)</title><addtitle>Plast Reconstr Surg</addtitle><description>BACKGROUND:De novo or rare transmitted mutations in the SMAD6 gene affect 7 percent of midline nonsyndromic synostosis patients. This study aimed to determine the neurocognitive sequelae of SMAD6 synostosis.
METHODS:Nonsyndromic synostosis patients 6 years or older with SMAD6 mutations and non-SMAD6 nonsyndromic synostosis controls were recruited. All patients completed a double-blinded neurodevelopmental battery (i.e., Wechsler Fundamentals, Wechsler Abbreviated Scale of Intelligence, Beery-Buktenica Developmental test), and parents/guardians completed behavioral surveys (Behavior Rating Inventory of Executive Function and Behavior Rating System for Children).
RESULTS:Twenty-eight patients participated10 known SMAD6 patients (average age, 10 years; 1 female; eight metopic and two sagittal; nine treated with cranial vault remodeling and one treated with strip craniectomy) and 18 non-SMAD6 controls (age, 9.5 years; three female; 12 metopic and six sagittal; 17 treated with cranial vault remodeling and one treated with strip craniectomy). There were no differences between any demographics. Testing age, surgical age, parental education, and household income correlated with cognition (p < 0.05). After controlling for these factors, SMAD6 patients performed worse on numerical operations (p = 0.046), performance intelligence quotient (p = 0.018), full-scale intelligence quotient (p = 0.010), and motor coordination (p = 0.043) compared to age/race/gender/synostosis/operation-matched controls. On behavioral surveys, SMAD6 patients scored worse on 14 assessments, including aggression, communication, and behavior.
CONCLUSIONS:This prospective double-blinded study revealed that neuropsychiatric development of nonsyndromic synostosis may be under genetic control. SMAD6 mutations led to poorer mathematics, performance intelligence quotient, full-scale intelligence quotient, and motor coordination, even after controlling for exogenous factors. Genetic testing may be critical for advocating early adjunctive neurodevelopmental therapy.
CLINICAL QUESTION/LEVEL OF EVIDENCE:Risk, II.</description><subject>Case-Control Studies</subject><subject>Child</subject><subject>Child Behavior</subject><subject>Child Development</subject><subject>Child, Preschool</subject><subject>Craniosynostoses - complications</subject><subject>Craniosynostoses - genetics</subject><subject>Craniosynostoses - surgery</subject><subject>Craniotomy - methods</subject><subject>Developmental Disabilities - diagnosis</subject><subject>Developmental Disabilities - genetics</subject><subject>Developmental Disabilities - prevention & control</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Infant</subject><subject>Intelligence Tests</subject><subject>Loss of Function Mutation</subject><subject>Male</subject><subject>Prospective Studies</subject><subject>Reconstructive Surgical Procedures - methods</subject><subject>Skull - surgery</subject><subject>Smad6 Protein - genetics</subject><subject>Treatment Outcome</subject><issn>0032-1052</issn><issn>1529-4242</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1LxDAQhoMo7vrxD0R69FJNJkljjrLqKviF6710k1m22jY1aV323xvdVcSDBoYw8Lwz8AwhB4weM6rVycPj5Jj-eBlneoMMmQSdChCwSYaUckgZlTAgOyE8U8oUz-Q2GXAmNWhJh-R6cnt2niVjbFy3bDF58GhL04XkDnvvLL5h5doamy4pm-TONWHZWO_q0iQjXzSli70LnQtl2CNbs6IKuL_-d8nT5cXT6Cq9uR9fj85uUiMo02kmNJsqyYUtrGWQianRyiipLYLSpjCnVmY4pWymrS4kVUaC0RKAAVAz47vkaDW29e61x9DldRkMVlXRoOtDDpyCyBQTWUTFCjXeheBxlre-rAu_zBnNPxzm0WH-22GMHa439NMa7XfoS1oETlfAwlUd-vBS9Qv0-RyLqpv_N1v8Ef3EopoUKMRjxS6NxRV_B4rFjSI</recordid><startdate>20200101</startdate><enddate>20200101</enddate><creator>Wu, Robin T.</creator><creator>Timberlake, Andrew T.</creator><creator>Abraham, Paul F.</creator><creator>Gabrick, Kyle S.</creator><creator>Lu, Xiaona</creator><creator>Peck, Connor J.</creator><creator>Sawh-Martinez, Rajendra F.</creator><creator>Steinbacher, Derek M.</creator><creator>Alperovich, Michael A.</creator><creator>Persing, John A.</creator><general>by the American Society of Plastic Surgeons</general><general>American Society of Plastic Surgeons</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20200101</creationdate><title>SMAD6 Genotype Predicts Neurodevelopment in Nonsyndromic Craniosynostosis</title><author>Wu, Robin T. ; Timberlake, Andrew T. ; Abraham, Paul F. ; Gabrick, Kyle S. ; Lu, Xiaona ; Peck, Connor J. ; Sawh-Martinez, Rajendra F. ; Steinbacher, Derek M. ; Alperovich, Michael A. ; Persing, John A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4019-6491b7534dadd1264bc97c759de279cac8d56eb01f9d9a507c52c95221220cf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Case-Control Studies</topic><topic>Child</topic><topic>Child Behavior</topic><topic>Child Development</topic><topic>Child, Preschool</topic><topic>Craniosynostoses - complications</topic><topic>Craniosynostoses - genetics</topic><topic>Craniosynostoses - surgery</topic><topic>Craniotomy - methods</topic><topic>Developmental Disabilities - diagnosis</topic><topic>Developmental Disabilities - genetics</topic><topic>Developmental Disabilities - prevention & control</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Humans</topic><topic>Infant</topic><topic>Intelligence Tests</topic><topic>Loss of Function Mutation</topic><topic>Male</topic><topic>Prospective Studies</topic><topic>Reconstructive Surgical Procedures - methods</topic><topic>Skull - surgery</topic><topic>Smad6 Protein - genetics</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Robin T.</creatorcontrib><creatorcontrib>Timberlake, Andrew T.</creatorcontrib><creatorcontrib>Abraham, Paul F.</creatorcontrib><creatorcontrib>Gabrick, Kyle S.</creatorcontrib><creatorcontrib>Lu, Xiaona</creatorcontrib><creatorcontrib>Peck, Connor J.</creatorcontrib><creatorcontrib>Sawh-Martinez, Rajendra F.</creatorcontrib><creatorcontrib>Steinbacher, Derek M.</creatorcontrib><creatorcontrib>Alperovich, Michael A.</creatorcontrib><creatorcontrib>Persing, John A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Plastic and reconstructive surgery (1963)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Robin T.</au><au>Timberlake, Andrew T.</au><au>Abraham, Paul F.</au><au>Gabrick, Kyle S.</au><au>Lu, Xiaona</au><au>Peck, Connor J.</au><au>Sawh-Martinez, Rajendra F.</au><au>Steinbacher, Derek M.</au><au>Alperovich, Michael A.</au><au>Persing, John A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SMAD6 Genotype Predicts Neurodevelopment in Nonsyndromic Craniosynostosis</atitle><jtitle>Plastic and reconstructive surgery (1963)</jtitle><addtitle>Plast Reconstr Surg</addtitle><date>2020-01-01</date><risdate>2020</risdate><volume>145</volume><issue>1</issue><spage>117e</spage><epage>125e</epage><pages>117e-125e</pages><issn>0032-1052</issn><eissn>1529-4242</eissn><abstract>BACKGROUND:De novo or rare transmitted mutations in the SMAD6 gene affect 7 percent of midline nonsyndromic synostosis patients. This study aimed to determine the neurocognitive sequelae of SMAD6 synostosis.
METHODS:Nonsyndromic synostosis patients 6 years or older with SMAD6 mutations and non-SMAD6 nonsyndromic synostosis controls were recruited. All patients completed a double-blinded neurodevelopmental battery (i.e., Wechsler Fundamentals, Wechsler Abbreviated Scale of Intelligence, Beery-Buktenica Developmental test), and parents/guardians completed behavioral surveys (Behavior Rating Inventory of Executive Function and Behavior Rating System for Children).
RESULTS:Twenty-eight patients participated10 known SMAD6 patients (average age, 10 years; 1 female; eight metopic and two sagittal; nine treated with cranial vault remodeling and one treated with strip craniectomy) and 18 non-SMAD6 controls (age, 9.5 years; three female; 12 metopic and six sagittal; 17 treated with cranial vault remodeling and one treated with strip craniectomy). There were no differences between any demographics. Testing age, surgical age, parental education, and household income correlated with cognition (p < 0.05). After controlling for these factors, SMAD6 patients performed worse on numerical operations (p = 0.046), performance intelligence quotient (p = 0.018), full-scale intelligence quotient (p = 0.010), and motor coordination (p = 0.043) compared to age/race/gender/synostosis/operation-matched controls. On behavioral surveys, SMAD6 patients scored worse on 14 assessments, including aggression, communication, and behavior.
CONCLUSIONS:This prospective double-blinded study revealed that neuropsychiatric development of nonsyndromic synostosis may be under genetic control. SMAD6 mutations led to poorer mathematics, performance intelligence quotient, full-scale intelligence quotient, and motor coordination, even after controlling for exogenous factors. Genetic testing may be critical for advocating early adjunctive neurodevelopmental therapy.
CLINICAL QUESTION/LEVEL OF EVIDENCE:Risk, II.</abstract><cop>United States</cop><pub>by the American Society of Plastic Surgeons</pub><pmid>31592950</pmid><doi>10.1097/PRS.0000000000006319</doi></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0032-1052 |
| ispartof | Plastic and reconstructive surgery (1963), 2020-01, Vol.145 (1), p.117e-125e |
| issn | 0032-1052 1529-4242 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2302467146 |
| source | MEDLINE; Journals@Ovid Complete |
| subjects | Case-Control Studies Child Child Behavior Child Development Child, Preschool Craniosynostoses - complications Craniosynostoses - genetics Craniosynostoses - surgery Craniotomy - methods Developmental Disabilities - diagnosis Developmental Disabilities - genetics Developmental Disabilities - prevention & control Double-Blind Method Female Follow-Up Studies Humans Infant Intelligence Tests Loss of Function Mutation Male Prospective Studies Reconstructive Surgical Procedures - methods Skull - surgery Smad6 Protein - genetics Treatment Outcome |
| title | SMAD6 Genotype Predicts Neurodevelopment in Nonsyndromic Craniosynostosis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T10%3A14%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=SMAD6%20Genotype%20Predicts%20Neurodevelopment%20in%20Nonsyndromic%20Craniosynostosis&rft.jtitle=Plastic%20and%20reconstructive%20surgery%20(1963)&rft.au=Wu,%20Robin%20T.&rft.date=2020-01-01&rft.volume=145&rft.issue=1&rft.spage=117e&rft.epage=125e&rft.pages=117e-125e&rft.issn=0032-1052&rft.eissn=1529-4242&rft_id=info:doi/10.1097/PRS.0000000000006319&rft_dat=%3Cproquest_cross%3E2302467146%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2302467146&rft_id=info:pmid/31592950&rfr_iscdi=true |