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Brunner syndrome(BRNRS)

MedGen UID:
208683
Concept ID:
C0796275
Disease or Syndrome
Synonyms: BRNRS; Monoamine oxidase A deficiency
SNOMED CT: Deficiency of monoamine oxidase A (718210003); Monoamine oxidase A deficiency (718210003); Brunner syndrome (718210003)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Gene (location): MAOA (Xp11.3)
 
Monarch Initiative: MONDO:0010379
OMIM®: 300615
Orphanet: ORPHA3057

Definition

Brunner syndrome (BRNRS) is an X-linked recessive disorder characterized by impulsive aggressiveness and mildly impaired intellectual development associated with MAOA deficiency (Brunner et al., 1993). [from OMIM]

Additional description

From MedlinePlus Genetics
Monoamine oxidase A deficiency is a rare disorder that occurs almost exclusively in males. It is characterized by mild intellectual disability and behavioral problems beginning in early childhood.

Most boys with monoamine oxidase A deficiency are less able to control their impulses than their peers, causing aggressive or violent outbursts. In addition, affected individuals may have features of other neurodevelopmental disorders, including autism spectrum disorder and attention-deficit/hyperactivity disorder (ADHD). These features can include obsessive behaviors, difficulty forming friendships, and problems focusing attention. Sleep problems, such as trouble falling asleep or night terrors, can also occur in monoamine oxidase A deficiency.

Some people with monoamine oxidase A deficiency have episodes of skin flushing, sweating, headaches, or diarrhea. Similar episodes can occur in female family members of males with monoamine oxidase A deficiency, although females do not experience other signs or symptoms of the condition.

In some cases, certain foods, such as cheese, appear to worsen symptoms of monoamine oxidase A deficiency.  https://medlineplus.gov/genetics/condition/monoamine-oxidase-a-deficiency

Clinical features

From HPO
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Aggressive behavior
MedGen UID:
1375
Concept ID:
C0001807
Individual Behavior
Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires).
Autism
MedGen UID:
13966
Concept ID:
C0004352
Mental or Behavioral Dysfunction
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). Levy et al. (2009) provided a general review of autism and autism spectrum disorder, including epidemiology, characteristics of the disorder, diagnosis, neurobiologic hypotheses for the etiology, genetics, and treatment options. Genetic Heterogeneity of Autism Autism is considered to be a complex multifactorial disorder involving many genes. Accordingly, several loci have been identified, some or all of which may contribute to the phenotype. Included in this entry is AUTS1, which has been mapped to chromosome 7q22. Other susceptibility loci include AUTS3 (608049), which maps to chromosome 13q14; AUTS4 (608636), which maps to chromosome 15q11; AUTS6 (609378), which maps to chromosome 17q11; AUTS7 (610676), which maps to chromosome 17q21; AUTS8 (607373), which maps to chromosome 3q25-q27; AUTS9 (611015), which maps to chromosome 7q31; AUTS10 (611016), which maps to chromosome 7q36; AUTS11 (610836), which maps to chromosome 1q41; AUTS12 (610838), which maps to chromosome 21p13-q11; AUTS13 (610908), which maps to chromosome 12q14; AUTS14A (611913), which has been found in patients with a deletion of a region of 16p11.2; AUTS14B (614671), which has been found in patients with a duplication of a region of 16p11.2; AUTS15 (612100), associated with mutation in the CNTNAP2 gene (604569) on chromosome 7q35-q36; AUTS16 (613410), associated with mutation in the SLC9A9 gene (608396) on chromosome 3q24; AUTS17 (613436), associated with mutation in the SHANK2 gene (603290) on chromosome 11q13; AUTS18 (615032), associated with mutation in the CHD8 gene (610528) on chromosome 14q11; AUTS19 (615091), associated with mutation in the EIF4E gene (133440) on chromosome 4q23; and AUTS20 (618830), associated with mutation in the NLGN1 gene (600568) on chromosome 3q26. (NOTE: the symbol 'AUTS2' has been used to refer to a gene on chromosome 7q11 (KIAA0442; 607270) and therefore is not used as a part of this autism locus series.) There are several X-linked forms of autism susceptibility: AUTSX1 (300425), associated with mutations in the NLGN3 gene (300336); AUTSX2 (300495), associated with mutations in NLGN4 (300427); AUTSX3 (300496), associated with mutations in MECP2 (300005); AUTSX4 (300830), associated with variation in the region on chromosome Xp22.11 containing the PTCHD1 gene (300828); AUTSX5 (300847), associated with mutations in the RPL10 gene (312173); and AUTSX6 (300872), associated with mutation in the TMLHE gene (300777). A locus on chromosome 2q (606053) associated with a phenotype including intellectual disability and speech deficits was formerly designated AUTS5. Folstein and Rosen-Sheidley (2001) reviewed the genetics of autism.
Headache
MedGen UID:
9149
Concept ID:
C0018681
Sign or Symptom
Cephalgia, or pain sensed in various parts of the head, not confined to the area of distribution of any nerve.
Impulsivity
MedGen UID:
43850
Concept ID:
C0021125
Mental or Behavioral Dysfunction
Acting on the spur of the moment or on a momentary basis without consideration of outcomes; having difficulty establishing or following plans; experiencing a sense of urgency and engaging in behavior that is uninhibited, cannot be inhibited, and is uncontrolled. The possibility of repression is inconceivable.
Self-injurious behavior
MedGen UID:
88371
Concept ID:
C0085271
Individual Behavior
Self-aggression.
Low frustration tolerance
MedGen UID:
108189
Concept ID:
C0548883
Mental or Behavioral Dysfunction
The feeling of frustration can be defined as an emotional reaction that occurs when a desired goal is not achieved. Frustration intolerance is defined as an age-inappropriate response to frustration, characterized by crying or temper tantrums in children, or aggressive or other undesirable behaviors.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Kinetic tremor
MedGen UID:
1638576
Concept ID:
C4551521
Sign or Symptom
Tremor that occurs during any voluntary movement. It may include visually or non-visually guided movements. Tremor during target directed movement is called intention tremor.
Flushing
MedGen UID:
5234
Concept ID:
C0016382
Sign or Symptom
Recurrent episodes of redness of the skin together with a sensation of warmth or burning of the affected areas of skin.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVBrunner syndrome
Follow this link to review classifications for Brunner syndrome in Orphanet.

Recent clinical studies

Etiology

Bortolato M, Floris G, Shih JC
J Neural Transm (Vienna) 2018 Nov;125(11):1589-1599. Epub 2018 May 10 doi: 10.1007/s00702-018-1888-y. PMID: 29748850Free PMC Article

Diagnosis

Minniti ML, Kalantari S, Pasca L, Bruno S, Arceri S, Novello E, Giorgio E, Rizzo V, Borgatti R, Valente EM, Pisani A, Orcesi S, Sirchia F
Am J Med Genet A 2024 Jan;194(1):82-87. Epub 2023 Sep 26 doi: 10.1002/ajmg.a.63413. PMID: 37750385
Marcos J, Renau N, Valverde O, Aznar-Laín G, Gracia-Rubio I, Gonzalez-Sepulveda M, Pérez-Jurado LA, Ventura R, Segura J, Pozo OJ
J Chromatogr A 2016 Feb 19;1434:91-101. Epub 2016 Jan 14 doi: 10.1016/j.chroma.2016.01.023. PMID: 26818237
Palmer EE, Leffler M, Rogers C, Shaw M, Carroll R, Earl J, Cheung NW, Champion B, Hu H, Haas SA, Kalscheuer VM, Gecz J, Field M
Clin Genet 2016 Jan;89(1):120-7. Epub 2015 Apr 19 doi: 10.1111/cge.12589. PMID: 25807999

Prognosis

Nilsson KW, Åslund C, Comasco E, Oreland L
J Neural Transm (Vienna) 2018 Nov;125(11):1601-1626. Epub 2018 Jun 7 doi: 10.1007/s00702-018-1892-2. PMID: 29881923Free PMC Article
Palmer EE, Leffler M, Rogers C, Shaw M, Carroll R, Earl J, Cheung NW, Champion B, Hu H, Haas SA, Kalscheuer VM, Gecz J, Field M
Clin Genet 2016 Jan;89(1):120-7. Epub 2015 Apr 19 doi: 10.1111/cge.12589. PMID: 25807999

Clinical prediction guides

Nilsson KW, Åslund C, Comasco E, Oreland L
J Neural Transm (Vienna) 2018 Nov;125(11):1601-1626. Epub 2018 Jun 7 doi: 10.1007/s00702-018-1892-2. PMID: 29881923Free PMC Article
Marcos J, Renau N, Valverde O, Aznar-Laín G, Gracia-Rubio I, Gonzalez-Sepulveda M, Pérez-Jurado LA, Ventura R, Segura J, Pozo OJ
J Chromatogr A 2016 Feb 19;1434:91-101. Epub 2016 Jan 14 doi: 10.1016/j.chroma.2016.01.023. PMID: 26818237
Palmer EE, Leffler M, Rogers C, Shaw M, Carroll R, Earl J, Cheung NW, Champion B, Hu H, Haas SA, Kalscheuer VM, Gecz J, Field M
Clin Genet 2016 Jan;89(1):120-7. Epub 2015 Apr 19 doi: 10.1111/cge.12589. PMID: 25807999
Piton A, Poquet H, Redin C, Masurel A, Lauer J, Muller J, Thevenon J, Herenger Y, Chancenotte S, Bonnet M, Pinoit JM, Huet F, Thauvin-Robinet C, Jaeger AS, Le Gras S, Jost B, Gérard B, Peoc'h K, Launay JM, Faivre L, Mandel JL
Eur J Hum Genet 2014 Jun;22(6):776-83. Epub 2013 Oct 30 doi: 10.1038/ejhg.2013.243. PMID: 24169519Free PMC Article
Scott AL, Bortolato M, Chen K, Shih JC
Neuroreport 2008 May 7;19(7):739-43. doi: 10.1097/WNR.0b013e3282fd6e88. PMID: 18418249Free PMC Article

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