Brunner syndrome

The following signs and symptoms occur in people with monoamine oxidase A deficiency, which causes Brunner syndrome:{{Cite web |title=Monoamine oxidase A deficiency |url=https://medlineplus.gov/genetics/condition/monoamine-oxidase-a-deficiency/ |access-date=23 February 2023 |website=MedlinePlus}}

• lack of impulse control
• aggressive or violent outbursts
• ASD or ADHD-like behavioral features
• obsessive behaviors
• difficulties forming friendships
• problems focusing attention
• sleep problems
• trouble falling asleep
• night terrors
• skin flushing
• sweating
• headaches
• diarrhea

Brunner syndrome is caused by a monoamine oxidase A (MAOA) deficiency, which leads to an excess of monoamines in the brain, such as serotonin, dopamine, and norepinephrine (noradrenaline). In both mice and humans, a mutation was located on the eighth exon of the MAO-A gene, which created a dysfunctional MAO-A gene.{{Cite journal |last=Scott |first=AL |last2=Bortolato, M |last3=Chen, K |last4=Shih, JC |author-link4=Jean Chen Shih |date=2008-05-07 |title=Novel monoamine oxidase A knock out mice with human-like spontaneous mutation. |journal=NeuroReport |volume=19 |issue=7 |pages=739–43 |doi=10.1097/WNR.0b013e3282fd6e88 |pmc=3435113 |pmid=18418249}} The regular function of MAO-A, breaking down monoamines, is disrupted, and monoamines build up within the brain. Mice that lacked a functional MAO-A gene displayed higher levels of aggression, in comparison to mice with a functional MAO-A gene.

Molecular Diagnosis establishing a mutation in the MAOA gene is possible,https://medlineplus.gov/genetics/condition/monoamine-oxidase-a-deficiency/#inheritance but establishing the clinical diagnosis is more challenging, since this condition is a variable spectrum disorder.

There is no restrictive treatment for Brunner syndrome, although a potential treatment can be established by checking the patient for signs and symptoms and analysing different catabolites in bodily fluids, that would be indicative of excess amount of monoamines in the body and mediating the symptoms by targeting therapy for the most problematic neurotransmitter. For example, if a patient is found having excess amount of serotonin in the blood (hyperserotonemia) and abnormal urine 5-HIAA levels then the patient might benefit from a serotonin reuptake inhibitor and dietary modifications. {{Cite journal |last=Palmer |first=E. E. |last2=Leffler |first2=M. |last3=Rogers |first3=C. |last4=Shaw |first4=M. |last5=Carroll |first5=R. |last6=Earl |first6=J. |last7=Cheung |first7=N. W. |last8=Champion |first8=B. |last9=Hu |first9=H. |last10=Haas |first10=S. A. |last11=Kalscheuer |first11=V. M. |last12=Gecz |first12=J. |last13=Field |first13=M. |date=January 2016 |title=New insights into Brunner syndrome and potential for targeted therapy |url=https://pubmed.ncbi.nlm.nih.gov/25807999/ |journal=Clinical Genetics |volume=89 |issue=1 |pages=120–127 |doi=10.1111/cge.12589 |issn=1399-0004 |pmid=25807999 |hdl-access=free |hdl=11858/00-001M-0000-002D-479D-D}}

Brunner Syndrome was described in 1993 by H.G. Brunner and his colleagues upon the discovery of a particular genetic defect in male members of a large Dutch family.{{Cite journal |vauthors=Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA |date=October 1993 |title=Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A |journal=Science |volume=262 |issue=5133 |pages=578–80 |bibcode=1993Sci...262..578B |doi=10.1126/science.8211186 |pmid=8211186}} Brunner found that all of the male family members with this defect reacted aggressively when angry, fearful, or frustrated. The defect discovered was later found to be a mutation in the gene that codes for monoamine oxidase A (MAOA gene). Brunner said that an "MAO-A deficiency is associated with a recognizable behavioural phenotype that included disturbed regulation of impulsive aggression".

A letter published by Hebebrand and Klug (1995){{Cite journal |vauthors=Hebebrand J, Klug B |date=September 1995 |title=Specification of the phenotype required for men with monoamine oxidase type A deficiency |journal=Hum. Genet. |volume=96 |issue=3 |pages=372–6 |doi=10.1007/BF00210430 |pmid=7649563 |s2cid=33294633}} criticized Brunner's findings for not using strict DSM criteria.

Brunner's findings have been used to argue that genetics, rather than decision-making processes, can cause criminal activity.{{Cite journal |vauthors=Halwani S, Krupp DB |year=2004 |title=The genetic defence: the impact of genetics on the concept of criminal responsibility |journal=Health Law J |volume=12 |pages=35–70 |pmid=16539076}} Evidence supporting the genetic defense stems from both Brunner's findings and a series of studies on mice. To prove the correlation between MAO-A deficiency and aggression in courts, it is often contended that individuals cannot be held accountable for their genes, and as a result, should not be held responsible for their dispositions and resulting actions.{{Cite journal |vauthors=Baker LA, Bezdjian S, Raine A |year=2006 |title=Behavioral genetics: the science of antisocial behavior |journal=Law Contemp Probl |volume=69 |issue=1–2 |pages=7–46 |pmc=2174903 |pmid=18176636}}

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{{Medical resources

| DiseasesDB = 32391

| ICD10 = E70.8

| ICD9 =

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| OMIM = 300615

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| Orphanet = 3057

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{{X-linked disorders}}

{{Amino acid metabolic pathology}}

Category:Rare syndromes

Category:Genetic syndromes

Category:Amino acid metabolism disorders