title: Dopamine dysfunction in 22q11 deletion syndrome: possible cause of motor symptoms.
abstract: 22q11 Deletion syndrome (22q11DS) is a neurogenetic disorder, resulting from a hemizygous microdeletion on the long arm of chromosome 22. In 22q11DS, the phenotypic expression is highly variable. Approximately one-third of all individuals with 22q11DS develop schizophrenia-like psychotic disorder. Among the genes in the deleted region, catechol-O-methyltransferase (COMT) has a particular relevance for psychiatric disorders: lower COMT enzymatic activity decreases the clearance of dopamine (DA), yielding higher levels of catecholamines in the central nervous system. Deficits in myelinogenesis and dysfunctions in the DA system could justify the white matter abnormalities in motor/premotor circuits described in 22q11DS. The alterations in DA could determine the high incidence of psychiatric disorders and the presence of neurological soft signs in 22q11DS. Neurological soft signs are defined as non-normative performance on an examination of motor and sensory tasks without focal neurological deficits. COMT haploinsufficiency, DA dysfunction, and white matter abnormalities may contribute toward the presence of neurological soft signs in 22q11DS.
authors.affiliation: aDepartment of System Medicine, Child Neurology and Psychiatry Unit, 'Tor Vergata' University of Rome bDepartment of Neuroscience, Unit of Child Neuropsychiatry, Children's Hospital Bambino Gesù, IRCCS, Rome, Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Casarelli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Minnei
authors.forename: Mariabernarda
authors.initials: M
authors.lastname: Pitzianti
authors.forename: Marco
authors.initials: M
authors.lastname: Armando
authors.forename: Maria
authors.initials: M
authors.lastname: Pontillo
authors.forename: Stefano
authors.initials: S
authors.lastname: Vicari
authors.forename: Augusto
authors.initials: A
authors.lastname: Pasini
mesh_terms: D058165:22q11 Deletion Syndrome / Q000150:complications* / Q000378:metabolism*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004298:Dopamine / Q000378:metabolism*; D057895:Haploinsufficiency; D006801:Humans; D010641:Phenotype; D011618:Psychotic Disorders / Q000235:genetics*; D066127:White Matter / Q000002:abnormalities
chemical_list: C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; D004298:Dopamine