title: Behavior of 10 patients with FG syndrome (Opitz-Kaveggia syndrome) and the p.R961W mutation in the MED12 gene.
abstract: Opitz and Kaveggia [Opitz and Kaveggia (1974); Z Kinderheilk 117:1-18] reported on a family of five affected males with distinctive facial appearance, mental retardation, macrocephaly, imperforate anus and hypotonia. Risheg et al. [Risheg et al. (2007); Nat Genet 39:451-453] identified an identical mutation (p.R961W) in MED12 in six families with Opitz-Kaveggia syndrome, including a surviving affected man from the family reported in 1974. The previously defined behavior phenotype of hyperactivity, affability, and excessive talkativeness is very frequent in young boys with this mutation, along with socially oriented, attention-seeking behaviors. We present case studies of two older males with FG syndrome and the p.R961W mutation to illustrate how their behavior changes with age. We also characterize the behavior of eight additional individuals with FG syndrome and this recurrent mutation in MED12 using the Vineland Adaptive Behavior Scales 2nd edition, the Reiss Profile of Fundamental Goals and Motivation Sensitivities, and the Achenbach Child Behavior Checklist. Males with this MED12 mutation had deficits in communication skills compared to their socialization and daily living skills. In addition, they were at increased risk for maladaptive behavior, with a propensity towards aggression, anxiety, and inattention. Based on the behavior phenotype in 10 males with this recurrent MED12 mutation, we offer specific recommendations and interventional strategies. Our findings reinforce the importance of testing for the p.R961W MED12 mutation in males who are suspected of having developmental and behavioral problems with a clinical phenotype that is consistent with FG syndrome.
authors.affiliation: Medical Genetics Institute, Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, California 90048, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Graham
authors.forename: Jeannie
authors.initials: J
authors.lastname: Visootsak
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Dykens
authors.forename: Lillie
authors.initials: L
authors.lastname: Huddleston
authors.forename: Robin D
authors.initials: RD
authors.lastname: Clark
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Jones
authors.forename: John B
authors.initials: JB
authors.lastname: Moeschler
authors.forename: John M
authors.initials: JM
authors.lastname: Opitz
authors.forename: Jackie
authors.initials: J
authors.lastname: Morford
authors.forename: Richard
authors.initials: R
authors.lastname: Simensen
authors.forename: R Curtis
authors.initials: RC
authors.lastname: Rogers
authors.forename: Charles E
authors.initials: CE
authors.lastname: Schwartz
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Friez
authors.forename: Roger E
authors.initials: RE
authors.lastname: Stevenson
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000523:psychology*; D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D001120:Arginine / Q000235:genetics / Q000378:metabolism; D002648:Child; D002653:Child Behavior Disorders / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D003142:Communication; D006801:Humans; D008297:Male; D056892:Mediator Complex; D038901:X-Linked Intellectual Disability / Q000150:complications / Q000235:genetics / Q000523:psychology*; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D012920:Social Behavior Disorders / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D012951:Socialization; D013577:Syndrome; D014364:Tryptophan / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: C460107:MED12 protein, human; D056892:Mediator Complex; D011988:Receptors, Thyroid Hormone; D014364:Tryptophan; D001120:Arginine