{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T14:35:06Z","timestamp":1784126106181,"version":"3.55.0"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,4,19]],"date-time":"2015-04-19T00:00:00Z","timestamp":1429401600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["628952"],"award-info":[{"award-number":["628952"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:p>We report two families with Brunner syndrome living in one state of Australia. The first family had a predicted protein\u2010truncating variant of monoamine oxidase A (<jats:italic><jats:styled-content style=\"fixed-case\">MAOA<\/jats:styled-content><\/jats:italic>) (<jats:styled-content style=\"fixed-case\">p.S251KfsX2<\/jats:styled-content>). Affected males had mild intellectual disability (<jats:styled-content style=\"fixed-case\">ID<\/jats:styled-content>), obsessive behaviour, limited friendships and were introverted and placid during clinical interview. The family disclosed episodic explosive aggression after a diagnosis was made. The second family had a missense variant in <jats:italic><jats:styled-content style=\"fixed-case\">MAOA<\/jats:styled-content><\/jats:italic> (<jats:styled-content style=\"fixed-case\">p.R45W<\/jats:styled-content>). Affected males had borderline\u2010mild <jats:styled-content style=\"fixed-case\">ID<\/jats:styled-content>, attention deficit disorder and limited friendships. One had a history of explosive aggression in childhood and episodic symptoms of flushing, headaches and diarrhoea. Their carrier mother had normal intelligence but similar episodic symptoms. Characteristic biochemical abnormalities included high serum serotonin and urinary metanephrines and low urinary 5\u2010hydroxyindoleacetic acid (5\u2010<jats:styled-content style=\"fixed-case\">HIAA<\/jats:styled-content>) and vanillylmandelic acid (<jats:styled-content style=\"fixed-case\">VMA<\/jats:styled-content>). Symptomatic individuals in the second family had particularly high serotonin levels, and treatment with a serotonin reuptake inhibitor and dietary modification resulted in reversal of biochemical abnormalities, reduction of \u2018serotonergic\u2019 symptoms and behavioural improvement. Brunner syndrome should be considered as a cause of mild <jats:styled-content style=\"fixed-case\">ID<\/jats:styled-content> with paroxysmal behavioural symptoms. It can be screened for with serum\/urine metanephrine and serotonin measurement. Cautious treatment with a serotonin reuptake inhibitor, dietary modifications and avoidance of medications contraindicated in patients on monoamine oxidase inhibitors can improve symptoms.<\/jats:p>","DOI":"10.1111\/cge.12589","type":"journal-article","created":{"date-parts":[[2015,3,24]],"date-time":"2015-03-24T20:58:26Z","timestamp":1427230706000},"page":"120-127","source":"Crossref","is-referenced-by-count":46,"title":["New insights into Brunner syndrome and potential for targeted therapy"],"prefix":"10.1111","volume":"89","author":[{"given":"E.E.","family":"Palmer","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics GOLD (Genetics of Learning Disability) service  Waratah New South Wales Australia"},{"name":"University of New South Wales  Waratah New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Leffler","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics GOLD (Genetics of Learning Disability) service  Waratah New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Rogers","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics GOLD (Genetics of Learning Disability) service  Waratah New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Shaw","sequence":"additional","affiliation":[{"name":"School of Paediatrics and Reproductive Health and Robinson Institute The University of Adelaide  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Carroll","sequence":"additional","affiliation":[{"name":"School of Paediatrics and Reproductive Health and Robinson Institute The University of Adelaide  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Earl","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health University of Sydney  Sydney New South Wales Australia"},{"name":"Department of Biochemistry The Children's Hospital at Westmead  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.W.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health University of Sydney  Sydney New South Wales Australia"},{"name":"Department of Endocrinology Nepean Hospital  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Champion","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health University of Sydney  Sydney New South Wales Australia"},{"name":"Department of Endocrinology Nepean Hospital  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.A.","family":"Haas","sequence":"additional","affiliation":[{"name":"Department of Computational Molecular Biology Max Planck Institute for Molecular Genetics  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.M.","family":"Kalscheuer","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Gecz","sequence":"additional","affiliation":[{"name":"School of Paediatrics and Reproductive Health and Robinson Institute The University of Adelaide  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Field","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics GOLD (Genetics of Learning Disability) service  Waratah New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,4,19]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"1032","article-title":"X\u2010linked borderline mental retardation with prominent behavioral disturbance: phenotype, genetic localization, and evidence for disturbed monoamine metabolism","volume":"52","author":"Brunner HG","year":"1993","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8211186"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2013.09.015"},{"key":"e_1_2_6_5_1","first-page":"155","article-title":"MAOA deficiency and abnormal behaviour: perspectives on an association","volume":"194","author":"Brunner HG","year":"1996","journal-title":"Ciba Found 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