Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Behavior of 10 patients with FG syndrome (Opitz-Kaveggia syndrome) and the p.R961W mutation in the MED12 gene. 1897 76

Opitz and Kaveggia [Opitz and Kaveggia (1974); Z Kinderheilkd 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); Nature Genetics 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 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 five adult males who were previously published with the clinical diagnosis of FG syndrome and then subsequently proven by Risheg et al. [Risheg et al. (2007); Nature Genetics 39:451-453] 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.
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PMID:Behavioral features in young adults with FG syndrome (Opitz-Kaveggia syndrome). 2098 78

The ASXL genes (ASXL1, ASXL2, and ASXL3) participate in body patterning during embryogenesis and encode proteins involved in epigenetic regulation and assembly of transcription factors to specific genomic loci. Germline de novo truncating variants in ASXL1 and ASXL3 have been respectively implicated in causing Bohring-Opitz and Bainbridge-Ropers syndromes, which result in overlapping features of severe intellectual disability and dysmorphic features. ASXL2 has not yet been associated with a human Mendelian disorder. In this study, we performed whole-exome sequencing in six unrelated probands with developmental delay, macrocephaly, and dysmorphic features. All six had de novo truncating variants in ASXL2. A careful review enabled the recognition of a specific phenotype consisting of macrocephaly, prominent eyes, arched eyebrows, hypertelorism, a glabellar nevus flammeus, neonatal feeding difficulties, hypotonia, and developmental disabilities. Although overlapping features with Bohring-Opitz and Bainbridge-Ropers syndromes exist, features that distinguish the ASXL2-associated condition from ASXL1- and ASXL3-related disorders are macrocephaly, absence of growth retardation, and more variability in the degree of intellectual disabilities. We were also able to demonstrate with mRNA studies that these variants are likely to exert a dominant-negative effect, given that both alleles are expressed in blood and the mutated ASXL2 transcripts escape nonsense-mediated decay. In conclusion, de novo truncating variants in ASXL2 underlie a neurodevelopmental syndrome with a clinically recognizable phenotype. This report expands the germline disorders that are linked to the ASXL genes.
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PMID:De Novo Truncating Variants in ASXL2 Are Associated with a Unique and Recognizable Clinical Phenotype. 2806 64


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