New insights into Brunner syndrome and potential for targeted therapy

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dc.contributor.authorPalmer, E.
dc.contributor.authorLeffler, M.
dc.contributor.authorRogers, C.
dc.contributor.authorShaw, M.
dc.contributor.authorCarroll, R.
dc.contributor.authorEarl, J.
dc.contributor.authorCheung, N.
dc.contributor.authorChampion, B.
dc.contributor.authorHu, H.
dc.contributor.authorHaas, S.
dc.contributor.authorKalscheuer, V.
dc.contributor.authorGecz, J.
dc.contributor.authorField, M.
dc.date.issued2016
dc.description.abstractWe report two families with Brunner syndrome living in one state of Australia. The first family had a predicted protein-truncating variant of monoamine oxidase A (MAOA) (p.S251KfsX2). Affected males had mild intellectual disability (ID), 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 MAOA (p.R45W). Affected males had borderline-mild ID, 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-hydroxyindoleacetic acid (5-HIAA) and vanillylmandelic acid (VMA). 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 'serotonergic' symptoms and behavioural improvement. Brunner syndrome should be considered as a cause of mild ID 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.
dc.description.statementofresponsibilityE.E. Palmer, M. Leffler, C. Rogers, M. Shaw, R. Carroll, J. Earl, N.W. Cheung, B. Champion, H. Hu, S.A. Haas, V.M. Kalscheuer, J. Gecz, and M. Field
dc.identifier.citationClinical Genetics, 2016; 89(1):120-127
dc.identifier.doi10.1111/cge.12589
dc.identifier.issn0009-9163
dc.identifier.issn1399-0004
dc.identifier.orcidShaw, M. [0000-0002-5060-190X]
dc.identifier.orcidCarroll, R. [0000-0002-6979-3710]
dc.identifier.orcidGecz, J. [0000-0002-7884-6861]
dc.identifier.urihttp://hdl.handle.net/2440/100253
dc.language.isoen
dc.publisherWiley
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/628952
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1041920
dc.rights© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
dc.source.urihttps://doi.org/10.1111/cge.12589
dc.subjectAutism spectrum disorder; Brunner syndrome; diagnosis; intellectual disability; MAO-A deficiency; serotonin; treatment
dc.titleNew insights into Brunner syndrome and potential for targeted therapy
dc.typeJournal article
pubs.publication-statusPublished

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