Behavioral features in young adults with FG syndrome (Opitz–Kaveggia syndrome)

Abstract

Opitz and Kaveggia [1974] reported on a family of 5 affected males with distinctive facial appearance, mental retardation, macrocephaly, imperforate anus and hypotonia. Risheg et al. [2007] identified an identical mutation (p.R961W) in MED12 in 6 families with Opitz-Kaveggia syndrome, including a surviving affected man from the original family reported in 1974. The previously described behavior phenotype of hyperactivity, affability, and excessive talkativeness is very frequent in young boys with FG syndrome, along with socially oriented, attention-seeking behaviors. We present case studies of 5 adult males who were previously published with the clinical diagnosis of FG syndrome and then subsequently proven by Risheg et al. [2007] to have the recurrent p.R961W mutation. These individuals had episodic and longstanding behavior patterns, sometimes aggressive or self-abusing, that occurred more frequently in puberty and early adulthood. We try to describe the triggers for these behaviors, indicate how these behaviors change with advancing age, and suggest specific recommendations and interventional strategies based on the clinical histories of affected adolescent males with FG syndrome [Graham et al., 2008;Clark et al., 2009]. Young men who exhibit these behaviors may benefit from a careful examination to detect medical problems, use of mood stabilizers if needed, and/or behavioral intervention. The transition to a community living situation can be challenging without careful planning and timely behavioral intervention. They remain impulsive and can have aggressive outbursts when making the transition to adult life, but these challenges can be managed, as demonstrated by these clinical histories.

MED12 related disorders

“…There is a consistent behavior phenotype in males with FG syndrome and this syndrome should be considered in males who present with developmental delay and a behavioral phenotype of hyperactivity, affability, and excessive talkativeness along with the distinctive clinical features of FG syndrome [Graham et al, 1999; Risheg et al, 2007; Clark et al, 2009; Graham et al, 2010]. Males with the recurrent R961W mutation in MED12 have strengths in socialization and daily living skills, despite their communicative deficits [Graham et al, 2008], and their strengths in socialization skills may mask their communicative deficits.…”

Novel MED12 gene somatic mutations in women from the Southern United States with symptomatic uterine fibroids

“…Germline mutations of MED12 gene have been reported in the Opitz–Kaveggia and Lujan–Fryns syndromes, which are characterized by congenital anomalies and intellectual disability (Taatjes 2010). Evidence has showed that MED12 performs both general and gene-specific roles to regulate gene expression (Graham et al 2010; Taatjes 2010). Nevertheless, the explanation for the high occurrence of MED12 gene mutations and the functional roles of these mutations in the tumorigenesis of uterine fibroids remain unknown.…”

MED12 mutations in human diseases

“…In 2007, Risheg found that there are frequent mutations in the twenty-fi rst exon of MED12 of FG syndrome patients, which results in C2881T and R961W mutations in the protein. Thereafter, the relationship between FG syndrome and mutations in MED12 was confi rmed by several other groups (Opitz and Kaveggia, 1974;Risheg et al, 2007;Graham et al, 2008;Graham et al, 2010). In addition, Rump P and colleagues found that three cousins suffering from FG syndrome all bear a mutation (G958E) in MED12, suggesting that the G958E mutation may also cause FG syndrome (Rump et al, 2011).…”