Brunner syndrome | |
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Other names | Monoamine oxidase A deficiency |
This condition is inherited in an X-linked recessive manner. |
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 pyromania, 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 additional families. [4]
The following signs and symptoms occur in people with monoamine oxidase A deficiency, which causes Brunner syndrome: [5]
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. [6] [7] 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. [7]
Upon suspicion of Brunner syndrome and after having eliminated other potential suspects via means of differential diagnosis, Brunner syndrome is diagnosed by genetic testing for specific mutations of the MAOA gene. Since the syndrome is so rare, it is usually only suspected and tested for if there are other diagnosed instances of the syndrome in one's direct family.[ citation needed ]
Progesterone & Rauwolfia serpentina (containing Reserpine) are a possible treatment as they both increase MAO-A activity.[ citation needed ]
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. [6] 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). [6] Brunner said that an "MAO-A deficiency is associated with a recognizable behavioural phenotype that included disturbed regulation of impulsive aggression". [6]
A letter published by Hebebrand and Klug (1995) [8] 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. [9] Evidence supporting the genetic defense stems from both Brunner's findings and a series of studies on mice. [10] 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. [9] [10]
Monoamine oxidases (MAO) are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The first such enzyme was discovered in 1928 by Mary Bernheim in the liver and was named tyramine oxidase. The MAOs belong to the protein family of flavin-containing amine oxidoreductases.
Noonan syndrome (NS) is a genetic disorder that may present with mildly unusual facial features, short height, congenital heart disease, bleeding problems, and skeletal malformations. Facial features include widely spaced eyes, light-colored eyes, low-set ears, a short neck, and a small lower jaw. Heart problems may include pulmonary valve stenosis. The breast bone may either protrude or be sunken, while the spine may be abnormally curved. Intelligence is often normal. Complications of NS can include leukemia.
Stickler syndrome is a group of rare genetic disorders affecting connective tissue, specifically collagen. Stickler syndrome is a subtype of collagenopathy, types II and XI. Stickler syndrome is characterized by distinctive facial abnormalities, ocular problems, hearing loss, and joint and skeletal problems. It was first studied and characterized by Gunnar B. Stickler in 1965.
ATP7A, also known as Menkes' protein (MNK), is a copper-transporting P-type ATPase which uses the energy arising from ATP hydrolysis to transport Cu(I) across cell membranes. The ATP7A protein is a transmembrane protein and is expressed in the intestine and all tissues except liver. In the intestine, ATP7A regulates Cu(I) absorption in the human body by transporting Cu(I) from the small intestine into the blood. In other tissues, ATP7A shuttles between the Golgi apparatus and the cell membrane to maintain proper Cu(I) concentrations in the cell and provides certain enzymes with Cu(I). The X-linked, inherited, lethal genetic disorder of the ATP7A gene causes Menkes disease, a copper deficiency resulting in early childhood death.
Monoamine oxidase A, also known as MAO-A, is an enzyme that in humans is encoded by the MAOA gene. This gene is one of two neighboring gene family members that encode mitochondrial enzymes which catalyze the oxidative deamination of amines, such as dopamine, norepinephrine, and serotonin. A mutation of this gene results in Brunner syndrome. This gene has also been associated with a variety of other psychiatric disorders, including antisocial behavior. Alternatively spliced transcript variants encoding multiple isoforms have been observed.
Ectrodactyly–ectodermal dysplasia–cleft syndrome, or EEC, and also referred to as EEC syndrome and split hand–split foot–ectodermal dysplasia–cleft syndrome is a rare form of ectodermal dysplasia, an autosomal dominant disorder inherited as a genetic trait. EEC is characterized by the triad of ectrodactyly, ectodermal dysplasia, and facial clefts. Other features noted in association with EEC include vesicoureteral reflux, recurrent urinary tract infections, obstruction of the nasolacrimal duct, decreased pigmentation of the hair and skin, missing or abnormal teeth, enamel hypoplasia, absent punctae in the lower eyelids, photophobia, occasional cognitive impairment and kidney anomalies, and conductive hearing loss.
The field of psychology has been greatly influenced by the study of genetics. Decades of research have demonstrated that both genetic and environmental factors play a role in a variety of behaviors in humans and animals. The genetic basis of aggression, however, remains poorly understood. Aggression is a multi-dimensional concept, but it can be generally defined as behavior that inflicts pain or harm on another.
Laminopathies are a group of rare genetic disorders caused by mutations in genes encoding proteins of the nuclear lamina. They are included in the more generic term nuclear envelopathies that was coined in 2000 for diseases associated with defects of the nuclear envelope. Since the first reports of laminopathies in the late 1990s, increased research efforts have started to uncover the vital role of nuclear envelope proteins in cell and tissue integrity in animals.
Neuronal migration protein doublecortin, also known as doublin or lissencephalin-X is a protein that in humans is encoded by the DCX gene.
Chromodomain-helicase-DNA-binding protein 7 is an ATP-dependent 'chromatin' or 'nucleosome' remodeling factor that in humans is encoded by the CHD7 gene.
Monoamine oxidase B, also known as MAOB, is an enzyme that in humans is encoded by the MAOB gene.
Eyes absent homolog 1 is a protein that in humans is encoded by the EYA1 gene.
Proline dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the PRODH gene.
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Neurogenetics studies the role of genetics in the development and function of the nervous system. It considers neural characteristics as phenotypes, and is mainly based on the observation that the nervous systems of individuals, even of those belonging to the same species, may not be identical. As the name implies, it draws aspects from both the studies of neuroscience and genetics, focusing in particular how the genetic code an organism carries affects its expressed traits. Mutations in this genetic sequence can have a wide range of effects on the quality of life of the individual. Neurological diseases, behavior and personality are all studied in the context of neurogenetics. The field of neurogenetics emerged in the mid to late 20th century with advances closely following advancements made in available technology. Currently, neurogenetics is the center of much research utilizing cutting edge techniques.
Marshall syndrome is a genetic disorder of the connective tissue that can cause hearing loss. The three most common areas to be affected are the eyes, which are uncommonly large, joints and the mouth and facial structures. Marshall syndrome and Stickler syndrome closely resemble each other; in fact they are so similar, some say they are the same. The condition is named for D. Weber.
A behaviour mutation is a genetic mutation that alters genes that control the way in which an organism behaves, causing their behavioural patterns to change.
Jean-Louis Mandel, born in Strasbourg on February 12, 1946, is a French medical doctor and geneticist, and heads a research team at the Institute of Genetics and Molecular and Cellular Biology (IGBMC). He has been in charge of the genetic diagnosis laboratory at the University Hospitals of Strasbourg since 1992, as well as a professor at the Collège de France since 2003.
The mitochondrial folate transporter (MTF) is a transport protein that facilitates the transfer of tetrahydrofolate across the inner mitochondrial membrane. It is encoded by the SLC25A32 gene and belongs to the mitochondrial carrier superfamily.
Xandra Owens Breakefield is an American neurologist who is a professor of neurology at the Harvard Medical School. Her research makes use of molecular genetics to understand the origins of inherited neurological diseases.