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.
FGS1 is typically 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.
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.
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.
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.
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