Brunner syndrome

Brunner syndrome
Classification and external resources
OMIM	300615
DiseasesDB	32391

Brunner syndrome is a rare genetic disorder associated with a mutation in the MAOA gene. It is characterized by lower than average IQ (typically about 85), problematic impulsive behavior (such as arson, hypersexuality and violence), sleep disorders and mood swings.^[1]^[2] It was identified in fourteen males from one family in 1993.^[1]^[3] It has since been discovered in two additional families.^[4]

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, 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.^[5]^[6] 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.^[6]

History

Brunner Syndrome was described in 1993 by H.G. Brunner et al upon the discovery of a particular genetic defect in male members of a large Dutch family.^[5] 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).^[5] Brunner said that an "MAO-A deficiency is associated with a recognizable behavioural phenotype that included disturbed regulation of impulsive aggression".^[5]

A letter published by Hebebrand and Klug (1995)^[7] 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.^[8] Evidence supporting the genetic defense stems from both Brunner's findings and a series of studies on mice.^[9] 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.^[8]^[9]

References

1 2 Hunter P (September 2010). "The psycho gene". EMBO Rep. 11 (9): 667–9. doi:10.1038/embor.2010.122. PMC 2933872. PMID 20805840.
↑ Online 'Mendelian Inheritance in Man' (OMIM) 300615
↑ Brunner HG, Nelen MR, van Zandvoort P, Abeling NGGM, van Gennip AH, Wolters EC, Kuiper MA, Ropers HH, van Oost BA (June 1993). "X-linked borderline mental retardation with prominent behavioral disturbance: phenotype, genetic localization, and evidence for disturbed monoamine metabolism". Am. J. Hum. Genet. 52 (6): 1032–9. PMC 1682278. PMID 8503438.
↑ Piton A, Redin C, Mandel JL (August 2013). "XLID-causing mutations and associated genes challenged in light of data from large-scale human exome sequencing". Am. J. Hum. Genet. 93 (2): 368–83. doi:10.1016/j.ajhg.2013.06.013. PMC 3738825. PMID 23871722.
1 2 3 4 Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA (October 1993). "Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A". Science 262 (5133): 578–80. doi:10.1126/science.8211186. PMID 8211186.
1 2 Scott, AL; Bortolato, M; Chen, K; Shih, JC (2008-05-07). "Novel monoamine oxidase A knock out mice with human-like spontaneous mutation.". NeuroReport 19 (7): 739–43. doi:10.1097/WNR.0b013e3282fd6e88. PMC 3435113. PMID 18418249.
↑ Hebebrand J, Klug B (September 1995). "Specification of the phenotype required for men with monoamine oxidase type A deficiency". Hum. Genet. 96 (3): 372–6. doi:10.1007/BF00210430. PMID 7649563.
1 2 Halwani S, Krupp DB (2004). "The genetic defence: the impact of genetics on the concept of criminal responsibility". Health Law J 12: 35–70. PMID 16539076.
1 2 Baker LA, Bezdjian S, Raine A (2006). "Behavioral genetics: the science of antisocial behavior". Law Contemp Probl 69 (1-2): 7–46. PMC 2174903. PMID 18176636.

Sex linkage: X-linked disorders

X-linked recessive

Immune	Chronic granulomatous disease (CYBB) Wiskott–Aldrich syndrome X-linked severe combined immunodeficiency X-linked agammaglobulinemia Hyper-IgM syndrome type 1 IPEX X-linked lymphoproliferative disease Properdin deficiency

Hematologic	Haemophilia A Haemophilia B X-linked sideroblastic anemia

Endocrine	Androgen insensitivity syndrome/Spinal and bulbar muscular atrophy KAL1 Kallmann syndrome X-linked adrenal hypoplasia congenita

Metabolic	Amino acid: Ornithine transcarbamylase deficiency Oculocerebrorenal syndrome Dyslipidemia: Adrenoleukodystrophy Carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency Pyruvate dehydrogenase deficiency Danon disease/glycogen storage disease Type IIb Lipid storage disorder: Fabry's disease Mucopolysaccharidosis: Hunter syndrome Purine-pyrimidine metabolism: Lesch–Nyhan syndrome Mineral: Menkes disease/Occipital horn syndrome

Nervous system	X-linked mental retardation: Coffin–Lowry syndrome MASA syndrome X-linked alpha thalassemia mental retardation syndrome Siderius X-linked mental retardation syndrome Eye disorders: Color blindness (red and green, but not blue) Ocular albinism (1) Norrie disease Choroideremia Other: Charcot–Marie–Tooth disease (CMTX2-3) Pelizaeus–Merzbacher disease SMAX2

Skin and related tissue	Dyskeratosis congenita Hypohidrotic ectodermal dysplasia (EDA) X-linked ichthyosis X-linked endothelial corneal dystrophy

Neuromuscular	Becker's muscular dystrophy/Duchenne Centronuclear myopathy (MTM1) Conradi–Hünermann syndrome Emery–Dreifuss muscular dystrophy 1

Urologic	Alport syndrome Dent's disease X-linked nephrogenic diabetes insipidus

Bone/tooth	AMELX Amelogenesis imperfecta

No primary system	Barth syndrome McLeod syndrome Smith–Fineman–Myers syndrome Simpson–Golabi–Behmel syndrome Mohr–Tranebjærg syndrome Nasodigitoacoustic syndrome

X-linked dominant

X-linked hypophosphatemia Focal dermal hypoplasia Fragile X syndrome Aicardi syndrome Incontinentia pigmenti Rett syndrome CHILD syndrome Lujan–Fryns syndrome Orofaciodigital syndrome 1 Craniofrontonasal dysplasia

Inborn error of amino acid metabolism (E70–E72, 270)

K→acetyl-CoA

Lysine/straight chain	Glutaric acidemia type 1 type 2 Hyperlysinemia Pipecolic acidemia Saccharopinuria

Leucine	3-hydroxy-3-methylglutaryl-CoA lyase deficiency 3-Methylcrotonyl-CoA carboxylase deficiency 3-Methylglutaconic aciduria 1 Isovaleric acidemia Maple syrup urine disease

Tryptophan	Hypertryptophanemia

G→pyruvate→citrate

Glycine	D-Glyceric acidemia Glutathione synthetase deficiency Sarcosinemia Glycine→Creatine: GAMT deficiency Glycine encephalopathy

G→glutamate→
α-ketoglutarate

Histidine	Carnosinemia Histidinemia Urocanic aciduria

Proline	Hyperprolinemia Prolidase deficiency

Glutamate/glutamine	SSADHD

G→propionyl-CoA→
succinyl-CoA

Valine	Hypervalinemia Isobutyryl-CoA dehydrogenase deficiency Maple syrup urine disease

Isoleucine	2-Methylbutyryl-CoA dehydrogenase deficiency Beta-ketothiolase deficiency Maple syrup urine disease

Methionine	Cystathioninuria Homocystinuria Hypermethioninemia

General BC/OA	Methylmalonic acidemia Methylmalonyl-CoA mutase deficiency Propionic acidemia

G→fumarate

Phenylalanine/tyrosine

Phenylketonuria	6-Pyruvoyltetrahydropterin synthase deficiency Tetrahydrobiopterin deficiency

Tyrosinemia	Alkaptonuria/Ochronosis Type I tyrosinemia Type II tyrosinemia Type III tyrosinemia/Hawkinsinuria

Tyrosine→Melanin	Albinism: Ocular albinism (1) Oculocutaneous albinism (Hermansky–Pudlak syndrome) Waardenburg syndrome

Tyrosine→Norepinephrine	Dopamine beta hydroxylase deficiency reverse: Brunner syndrome

G→oxaloacetate

Urea cycle/Hyperammonemia (arginine aspartate)	Argininemia Argininosuccinic aciduria Carbamoyl phosphate synthetase I deficiency Citrullinemia N-Acetylglutamate synthase deficiency Ornithine transcarbamylase deficiency/translocase deficiency

Transport/
IE of RTT

Other

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