Brunner syndrome is a rare

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosome abnormality. Although polygenic disorders ...

associated with a

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

in the MAOA gene. It is characterized by lower than average IQ (typically about 85), problematic impulsive behavior (such as

pyromania Pyromania is an impulse-control disorder in which individuals repeatedly fail to resist impulses to deliberately start fires, to relieve some tension or for instant gratification. The term ''pyromania'' comes from the Greek word (''pyr'', 'f ...

, hypersexuality and violence), sleep disorders and mood swings. It was identified in fourteen males from one family in 1993. It has since been discovered in additional families.

Signs and symptoms

The following signs and symptoms occur in people with monoamine oxidase A deficiency, which causes Brunner syndrome: * lack of impulse control * aggressive or violent outbursts * ASD or

ADHD Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by symptoms of inattention, hyperactivity, impulsivity, and emotional dysregulation that are excessive and pervasive, impairing in multiple ...

-like behavioral features ** obsessive behaviors ** difficulties forming friendships ** problems focusing attention * sleep problems ** trouble falling asleep ** night terrors * skin flushing * sweating * headaches * diarrhea

Causes

Brunner syndrome is caused by a monoamine oxidase A (MAOA) deficiency, which leads to an excess of monoamines in the brain, such as

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

, and

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

(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. 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.

Diagnosis

Molecular Diagnosis establishing a mutation in the MAOA gene is possible, but establishing the clinical diagnosis is more challenging, since this condition is a variable spectrum disorder.

Treatment

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 A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

. 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.

History

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. 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) criticized Brunner's findings for not using strict DSM criteria.

Society and culture

Brunner's findings have been used to argue that genetics, rather than decision-making processes, can cause criminal activity. 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.

References

External links

{{Amino acid metabolic pathology Rare syndromes Genetic syndromes Amino acid metabolism disorders