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FG Syndrome Type 1

NORD is very grateful to Michael J. Lyons, MD, Assistant Clinical Geneticist, Greenwood Genetic Center, for assistance in the preparation of this report.

Synonyms of FG Syndrome Type 1

  • FGS1
  • Opitz-Kaveggia syndrome

Disorder Subdivisions

  • No subdivisions found.

General Discussion

FG syndrome type 1 (FGS1) is an X-linked genetic disorder that is characterized by poor muscle tone (hypotonia), intellectual disability, constipation and or anal anomalies and complete or partial absence of the part of the brain that connects the two hemispheres of the brain (corpus callosum). Other features of the disorder are small and simple ears, tall and prominent forehead, wide and flat thumbs and great toes and downslanting eyes.

FGS1 is an X-linked genetic disorder caused by a recurrent abnormality (mutation) in the MED12 gene. The spectrum of disorders caused by mutations in this gene is still being defined. Some individuals previously diagnosed with FG syndrome do not have a MED12 gene mutation and, therefore, probably have a different reason for intellectual disability.

Symptoms

FG syndrome type 1 (FGS1) is an X-linked genetic disorder that is characterized by poor muscle tone (hypotonia), intellectual disability, constipation and or anal anomalies and complete or partial absence of the part of the brain that connects the two hemispheres of the brain (corpus callosum). Other features of the disorder are small and simple ears, tall and prominent forehead, wide and flat thumbs and great toes and downslanting eyes. Additional features may include a large head (macrocephaly), widely spaced eyes (ocular hypertelorism) and upswept frontal hair. Seizures and congenital heart defects have also been reported.

Individuals with FGS1 often have characteristic behaviors that can include hyperactivity, friendliness and attention seeking.

Causes

FGS1 is caused by a recurrent abnormality (mutation) in the MED12 gene on the X chromosome located at Xq13. The MED12 gene is responsible for production of the MED12 (TRAP230) protein that is involved in the regulation of transcription.

FGS1 is an X-linked genetic disorder. X-linked genetic disorders are conditions caused by an abnormal gene on the X chromosome and occur mostly in males. Females that have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes and one is inactivated so that the genes on that chromosome are nonfunctioning. It is usually the X chromosome with the abnormal gene that is inactivated. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a disease gene he will develop the disease. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.

Males with X-linked disorders pass the disease gene to all of their daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring.

Affected Populations

The prevalence of FGS1 is unknown. The spectrum of disorders caused by mutations in this gene is still being defined. Some individuals previously diagnosed with FG syndrome do not have a MED12 gene mutation and, therefore, probably have a different reason for intellectual disability.

Related Disorders

Symptoms of the following disorders can be similar to those of FGS1 syndrome. Comparisons may be useful for a differential diagnosis:

Lujan syndrome is an X-linked genetic disorder in the spectrum of disorders caused by mutations in the MED12 gene. This condition is characterized by intellectual disability, hypotonia, large head, tall and thin body, long and thin face and high and narrow palate. Additional features that may be present include small jaw, long hands with hyperextensible digits, abnormalities of the corpus callosum and nasal speech.

X-linked Opitz G/BBB syndrome is an X-linked genetic condition characterized by multiple birth defects including facial anomalies, abnormalities involving the trachea, larynx and esophagus and abnormalities of the genitourinary system. Cleft lip and palate are also common. Developmental delay and intellectual disability occur in about half of those affected. Heart defects, imperforate anus and defects in the midline of the brain can also occur.

Standard Therapies

Diagnosis
FGS1 syndrome is suspected based on the presence of physical characteristics. Molecular genetic testing for the MED12 gene is available and is the only way to confirm the diagnosis.

Treatment
The symptoms of FGS1 syndrome are treated individually. This usually involves care by a team of providers including a pediatrician, neurologist, cardiologist, surgeon, gastroenterologist and psychologist. Early intervention with physical, occupational and speech therapy should be initiated as soon as possible.

Genetic counseling is recommended for affected individuals and their family members.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Organizations related to FG Syndrome Type 1

References

TEXTBOOKS
Graham JM Jr. FG Syndrome In: The NORD Guide to Rare Disorders, Philadelphia: Lippincott, Williams and Wilkins, 2003:193-4.

JOURNAL ARTICLES
Clark RD, Graham JM Jr, et al. FG syndrome, an X-linked multiple congenital anomaly syndrome: The clinical phenotype and an algorithm for diagnostic testing. Genet Med. 2009 Nov;11(11):769-77.

Risheg H, Graham JM, Clark RD, et al. A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome. Nat Genet 2007;39:451-3.

Schwartz CE, Tarpay PS, Lubs HA, et al. The original Lujan syndrome family has a novel missense mutation (p.N1007S) in the MED12 gene. J Med Genet A 2007;44:472-7.
Battaglia A, Chines C and Carey JC. The FG syndrome:Report of a large Italian series. Am J Med Genet 2006;140A:2075-9.

Jehee, FS, Rosenberg C, Krepischi-Santos, AC, et al. An Xq22.3 duplication detected by comparative genomic hybridization microarray (Array-CGH) defines in a new locus (FGS5) for FG syndrome. Am J Med Genet 2005;139A:221-6.

Piluso G, Carella M, D'Avanzo M, et al. Genetic heterogeneity of FG syndrome: a fourth locus (FGS4) maps to Xp11.4-p11.3 in an Italian family. Hum Genet 2003;112(2):124-30.

Ozonoff S, Williams BJ, Rauch AM, et al. Behavioral phenotype of FG syndrome: cognition, personality and behavior in eleven boys. Am J Med Genet 2000;97:112-118.

Meroni G, Cainarca S, Berti C, et al. Identification and characterization of proteins that interact with midin, the Opitz syndrome gene product. Am Soc Hum Genet Program and Abstract 2000;abstract 959: p. 183.

Graham JM Jr, Superneau D, Rogers RC, et al. Clinical and behavioral characteristics in FG syndrome. Am J Med Genet 1999;85:470-475.

Opitz JM, Richieri-da Costa A, Aase JM, et al. FG syndrome update 1998: note of 5 new patients and bibliography. Am J Med Genet 1998;30:309-328.

Graham JM Jr, Tackels, D, Dibbern K, et al. FG syndrome: report of three new families with linkage to Xq12-q21.1 Am J Med Genet 1998;80:145-156.Briault S, Hill R, Shrimpton A, et al. A gene for FG syndrome maps in the Xq12-X21.31 region. Am J Med Genet 1997;73:87-90.

Briault S, Hill R, Shrimpton A, et al. A gene for FG syndrome maps in the Xq12-X21.31 region. Am J Med Genet 1997;73:87-90.

Kato R, Niikawa N, Nagai T, et al. Japanese kindred with FG syndrome [letter]. Am J Med Genet 1994;52:242-243.

FROM THE INTERNET
Lyons MJ.. MED12-Related Disorders. Last update: July 14, 2009. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Available at http://www.genetests.org . Accessed12/11.

Opitz JM. FG Syndrome. Orphanet Encyclopedia; Last updated 7/03. http://www.orpha.net/data/patho/Pro/en/FGSyndrome-FRenPro1053.pdf

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore, MD: The Johns Hopkins University; Entry No. 305450; Last Update1/7/10. http://omim.org/entry/305450

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Report last updated: 2012/01/05 00:00:00 GMT+0

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