FG syndrome: Report of three new families with linkage to xq12-q22.1

Graham, John M.; Tackels, Darci; Dibbern, Kurt; Superneau, Duane; Rogers, Curtis; Corning, Ken; Schwartz, Charles E.

doi:10.1002/(sici)1096-8628(19981102)80:2<145::aid-ajmg11>3.0.co;2-3

Cited by 32 publications

(11 citation statements)

References 25 publications

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“…We recently described clinical findings in three additional families with FG syndrome and confirmed the localization of a gene for the FG syndrome in Xq12-q21 [Briault et al, 1997;Graham et al, 1998]. Using these same families and one additional sporadic case of FG syndrome, herein we compare the behavior and personality characteristics of six FG boys with other agematched mentally retarded boys with Down syndrome, Prader-Willi syndrome, nonspecific mental retardation, and Williams syndrome.…”

Section: Introductionmentioning

confidence: 62%

Clinical and behavioral characteristics in FG syndrome

Graham¹,

Superneau²,

Rogers³

et al. 1999

Am. J. Med. Genet.

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FG syndrome is a rare X-linked recessive form of mental retardation, first described by Opitz and Kaveggia in 1974. Based on over 50 reported cases, FG syndrome is associated with agenesis of the corpus callosum, minor facial anomalies (high, broad forehead with frontal cowlick, ocular hypertelorism, down-slanted palpebral fissures, and small cupped auricles), relative macrocephaly, broad thumbs and halluces, and prominent fetal fingertip pads. Affected individuals manifest neonatal hypotonia and severe constipation, which usually resolves during mid-childhood. The hypotonia with joint hyperlaxity evolves into spasticity with joint contractures in later life. Affability, hyperactivity, and excessive talkativeness are noted frequently in patients with FG syndrome. Recently, we described three additional families (six additional patients) with FG syndrome who support the localization of a gene for the FG syndrome in chromosome region Xq12-q21 [Graham JM Jr, Tackels D, Dibbern K, Superneau D, Rodgers C, Corning K, Schwartz CE. 1998. Am J Med Genet 80:145-156.]. Using these same families and one additional sporadic case of FG syndrome, we compared behavioral and personality characteristics of 6 FG boys with other boys with syndromic and nonsyndromic mental retardation: eight with Down syndrome, seven with Prader-Willi syndrome, eight with nonspecific mental retardation, and 13 with Williams syndrome. Using the Vineland Adaptive Behavior Scales, the Reiss Personality Profiles, and the Achenbach Child Behavior Checklist, parents were asked to characterize the behavior and personality of their boys from ages 4 to 10 years. When compared with Williams syndrome, the FG boys had fewer internalizing behaviors and were significantly less anxious and withdrawn but had similar socially oriented, attention-seeking behaviors. On the Reiss Profile, FG boys were also quite similar to Williams syndrome boys. On the Vineland Scales, FG boys demonstrated significant relative strengths in their socialization skills, consistent with their personality, tending to confirm previous descriptions of their personalities.

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Section: Introductionmentioning

confidence: 62%

Clinical and behavioral characteristics in FG syndrome

Graham¹,

Superneau²,

Rogers³

et al. 1999

Am. J. Med. Genet.

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“…They also noted the distinctive affable, outgoing personality in surviving males. Later reports by McCardle and Wilson [1993]; and Graham et al [1998] (Family 1 and Family 3) confirmed the distinctive features of FG syndrome associated with the recurrent missense mutation (c.2881C>T, p.R961W) in MED12. …”

Section: Opitz-kaveggia (Fg) Syndromementioning

confidence: 70%

“…FG syndrome facial features from Case 1 from Graham et al [1998] shown as a child (A) and in late adolescence (B).…”

Section: Figurementioning

confidence: 99%

MED12 related disorders

Graham

Schwartz

2013

American J of Med Genetics Pt A

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MED12 is a member of the large Mediator complex, which has a critical and central role in RNA polymerase II transcription. As a multiprotien complex, Mediator regulates signals involved in cell growth, development and differentiation, and it is involved in a protein network required for extraneuronal gene silencing and also functions as a direct suppressor of Gli3-dependent Sonic hedgehog signaling. This may may explain its role in several different X-linked intellectual disability syndromes that share some overlapping clinical features. This review will compare and contrast four different clinical conditions that have been associated with different mutations in MED12, which is located at Xq13. To date, these conditions include Opitz–Kaveggia (FG) syndrome, Lujan syndrome, Ohdo syndrome (Maat-Kievit-Brunner type, or OSMKB), and one large family with profound X-linked intellectual disability due to a novel c.5898insC frameshift mutation that unlike the other 3 syndromes, resulted in affected female carriers and truncation of the MED12 protein. It is likely that more MED12 mutations will be detected in sporadic patients and X-linked families with intellectual disability and dysmorphic features as exome sequencing becomes more commonly utilized, and this overview of MED12-related disorders may help to correlate MED12 genotypes with clinical findings.

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“…1 Family 4, III-11 was first reported by Riccardi et al 5 as patient I-6. Family 5, II-1, II-3, and II-10 were reported by Keller et al 4 Family 6, III-3 was reported by McCardle and Wilson 6 as J.B. Family 7 was reported by Graham et al 8 as Family 1. Family 8 was reported by Graham et al 8 as Family 3.…”

Section: Figmentioning

confidence: 90%

“…Family 5, II-1, II-3, and II-10 were reported by Keller et al 4 Family 6, III-3 was reported by McCardle and Wilson 6 as J.B. Family 7 was reported by Graham et al 8 as Family 1. Family 8 was reported by Graham et al 8 as Family 3. Family 9 was reported by Graham et al 9 and by Opitz et al 10 as Family 3, Patient 4.…”

Section: Figmentioning

confidence: 90%

FG syndrome, an X-linked multiple congenital anomaly syndrome: The clinical phenotype and an algorithm for diagnostic testing

Clark

Graham

Friez

et al. 2009

Genetics in Medicine

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FG syndrome is a rare X-linked multiple congenital anomaly-cognitive impairment disorder caused by the p.R961W mutation in the MED12 gene. We identified all known patients with this mutation to delineate their clinical phenotype and devise a clinical algorithm to facilitate molecular diagnosis. We ascertained 23 males with the p.R961W mutation in MED12 from 9 previously reported FG syndrome families and 1 new family. Six patients are reviewed in detail. These 23 patients were compared with 48 MED12 mutation-negative patients, who had the clinical diagnosis of FG syndrome. Traits that best discriminated between these two groups were chosen to develop an algorithm with high sensitivity and specificity for the p.R961W MED12 mutation. FG syndrome has a recognizable dysmorphic phenotype with a high incidence of congenital anomalies. A family history of X-linked mental retardation, deceased male infants, and/or multiple fetal losses was documented in all families. The algorithm identifies the p.R961W MED12 mutation-positive group with 100% sensitivity and 90% spec-ificity. The clinical phenotype of FG syndrome defines a recognizable pattern of X-linked multiple congenital anomalies and cognitive impairment. This algorithm can assist the clinician in selecting the patients for testing who are most likely to have the recurrent p.R961W MED12 mutation.

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FG syndrome: Report of three new families with linkage to xq12-q22.1

Cited by 32 publications

References 25 publications

Clinical and behavioral characteristics in FG syndrome

Clinical and behavioral characteristics in FG syndrome

MED12 related disorders

FG syndrome, an X-linked multiple congenital anomaly syndrome: The clinical phenotype and an algorithm for diagnostic testing

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