FG syndrome

FG syndrome is a genetic condition that affects many parts of the body and occurs almost exclusively in males. "FG" represents the surname initials of the first family diagnosed with the disorder.

FG syndrome affects intelligence and behavior. Almost everyone with the condition has intellectual disability, which ranges from mild to severe. Affected individuals tend to be friendly, inquisitive, and hyperactive, with a short attention span. Compared to people with other forms of intellectual disability, their socialization and daily living skills are strong, while verbal communication and language skills tend to be weaker.

The physical features of FG syndrome include weak muscle tone (hypotonia), broad thumbs and great toes, and abnormalities of the tissue connecting the left and right halves of the brain (the corpus callosum). Most affected individuals have constipation and/or abnormalities of the anus, such as an obstruction of the anal opening (imperforate anus). People with FG syndrome also tend to have a distinctive facial appearance including small, simple ears; a tall, prominent forehead; and outside corners of the eyes that point downward (down-slanting palpebral fissures).

Other features seen in some people with FG syndrome include widely set eyes (hypertelorism), an upswept frontal hairline, and a large head compared to body size (relative macrocephaly). Medical problems including heart defects, seizures, undescended testes (cryptorchidism), and a soft outpouching in the lower abdomen (an inguinal hernia) have also been reported in some affected individuals.

The prevalence of FG syndrome is unknown, although several hundred cases have been reported worldwide. Researchers suspect that FG syndrome may be overdiagnosed because many of its signs and symptoms are also seen with other disorders.

Researchers have identified five regions of the X chromosome that are linked to FG syndrome in affected families. In one of these regions, a mutation in a particular gene called MED12 has been found to cause the disorder. Researchers are investigating genes in other regions of the X chromosome that may also be associated with FG syndrome.

The MED12 gene provides instructions for making a protein that helps regulate gene activity. Specifically, the MED12 protein forms part of a large complex (a group of proteins that work together) that turns genes on and off. The MED12 protein is thought to play an essential role in development both before and after birth.

Researchers have identified one mutation in the MED12 gene in several people with FG syndrome. Although the mutation alters the structure of the MED12 protein, it is unclear how this change leads to intellectual disability, behavioral changes, and the physical features associated with this condition.

Read more about the MED12 gene.

FG syndrome is inherited in an X-linked recessive pattern. The genes likely associated with this disorder, including MED12, are located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation usually must occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of a gene on the X chromosome, males are affected by X-linked recessive disorders much more frequently than females. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.