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

Clark, Robin D.; Graham, John M.; Friez, Michael J.; Hoo, Joe J.; Jones, Kenneth Lyons; McKeown, Carole; Moeschler, John B.; Raymond, F. Lucy; Rogers, R. Curtis; Schwartz, Charles E.; Battaglia, Agatino; Lyons, Michael J.; Stevenson, Roger E.

doi:10.1097/gim.0b013e3181bd3d90

Cited by 33 publications

(30 citation statements)

References 18 publications

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“… a With a positive family history, four clinical criteria are required in children under age 5 years, and five clinical criteria (including criterion 4) are required in older subjects. For more details on this algorithm, see Clark et al (8). …”

Section: Discussionmentioning

confidence: 99%

A novel mutation in MED12 causes FG syndrome (Opitz-Kaveggia syndrome)

Rump¹,

Niessen²,

Verbruggen

et al. 2011

Clinical Genetics

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Opitz-Kaveggia syndrome is a rare X-linked multiple congenital anomalies and intellectual disability disorder caused by the recurrent p.R961W mutation in the MED12 gene. Twenty-three affected males from 10 families with this mutation in the MED12 gene have been described so far. Here we report on a new family with three affected cousins, in which we identified a novel MED12 mutation (p.G958E). This is the first demonstration that other mutations in this gene can also lead to Opitz-Kaveggia syndrome. The clinical phenotype of these three new cases is reviewed in detail and compared with the previous reported cases.

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Section: Discussionmentioning

confidence: 99%

A novel mutation in MED12 causes FG syndrome (Opitz-Kaveggia syndrome)

Rump¹,

Niessen²,

Verbruggen

et al. 2011

Clinical Genetics

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“…Somatic findings: Male sex, developmental delay (younger than 3 years of age) or cognitive impairment/intellectual disability (older than 3 years of age), malformations of the anus, heart, or skeleton, and characteristic craniofacial dysmorphic features including relative macrocephaly, dolichocephaly, tall forehead, frontal hair upsweep, long narrow face, small ears, puffy eyelids, and open mouth …”

Section: Glossarymentioning

confidence: 99%

Neuroimaging Findings in Pediatric Genetic Skeletal Disorders: A Review

Wagner

Poretti

Benson

et al. 2016

Journal of Neuroimaging

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Genetic skeletal disorders (GSDs) are a heterogeneous group characterized by an intrinsic abnormality in growth and (re-)modeling of cartilage and bone. A large subgroup of GSDs has additional involvement of other structures/organs beside the skeleton, such as the central nervous system (CNS). CNS abnormalities have an important role in long-term prognosis of children with GSDs and should consequently not be missed. Sensitive and specific identification of CNS lesions while evaluating a child with a GSD requires a detailed knowledge of the possible associated CNS abnormalities. Here, we provide a pattern-recognition approach for neuroimaging findings in GSDs guided by the obvious skeletal manifestations of GSD. In particular, we summarize which CNS findings should be ruled out with each GSD. The diseases (n = 180) are classified based on the skeletal involvement (1. abnormal metaphysis or epiphysis, 2. abnormal size/number of bones, 3. abnormal shape of bones and joints, and 4. abnormal dynamic or structural changes). For each disease, skeletal involvement was defined in accordance with Online Mendelian Inheritance in Man. Morphological CNS involvement has been described based on extensive literature search. Selected examples will be shown based on prevalence of the diseases and significance of the CNS involvement. CNS involvement is common in GSDs. A wide spectrum of morphological abnormalities is associated with GSDs. Early diagnosis of CNS involvement is important in the management of children with GSDs. This pattern-recognition approach aims to assist and guide physicians in the diagnostic work-up of CNS involvement in children with GSDs and their management.

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“…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.…”

Section: Opitz-kaveggia (Fg) Syndromementioning

confidence: 99%

“…Currently, 10 families with FG syndrome and the recurrent p.R961W mutation in MED12 have been reported (including a total of 23 affected males), and diagnostic criteria have been proposed [Clark et al, 2009]. A family history of X-linked mental retardation, deceased male infants and/or multiple fetal losses was documented in all families.…”

Section: Opitz-kaveggia (Fg) Syndromementioning

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

Cited by 33 publications

References 18 publications

A novel mutation in MED12 causes FG syndrome (Opitz-Kaveggia syndrome)

A novel mutation in MED12 causes FG syndrome (Opitz-Kaveggia syndrome)

Neuroimaging Findings in Pediatric Genetic Skeletal Disorders: A Review

MED12 related disorders

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