FG syndrome

Definition

FG syndrome (FGS) is a genetic disorder characterized by mental retardation, low muscle tone (hypotonia), large head, constipation, and anal abnormalities.

Description

FGS refers to a rare genetic condition that has a variety of physical and mental symptoms. Most individuals affected by FGS have symptoms including mental retardation, low muscle tone, brain abnormalities (partial agenesis of the corpus callosum), seizures, large head, characteristic facial features, large intestinal and anal abnormalities, constipation, short stature, joints that tend to stay in one place (fixed), broad big toes, and light and dark skin streaking. The syndrome was first described by Opitz and Kaveggia in 1974 based on physical findings and family history. All of these features appear to be caused by mutated or changed genes on the X chromosome . Although the full effect of the mutation or change in the gene is not fully understood, the mutations are believed to interrupt the genes' normal functions in the brain, digestive tract, and muscle tissue.

Other names for FG syndrome include Opitz-Kaveggia Syndrome and Keller syndrome.

Genetic profile

FG syndrome (FGS) is caused by mutations on the long arm of the X-chromosome. Studies in 1998 and 2000 found that individuals affected by FGS can have a mutation on the X-chromosome in two different locations on the long arm (q) of the X-chromosome: Xq12-Xq21 [called FGS1] and Xq28 [called FGS2]. When a set of symptoms are caused by gene mutations at different locations, the disorder is called heterogeneous. Although a gene mutation causing FGS can appear in an individual for the first time and is not found in the affected individual's parents, most cases of FGS are inherited.

Since both possible gene mutations are found on the X chromosome, FGS is inherited in an X-linked recessive pattern. Every individual has approximately 30,000–35,000 genes that tell their bodies how to form and function. Each gene is present in pairs, since one is inherited from their mother and one is inherited from their father. Females have two X chromosomes, while males have a single X chromosome and Y chromosome. In other words, females receive two copies of the genetic information stored on the X chromosome. When a female inherits the gene for an X-linked recessive condition, she is known as a "carrier." She usually has no problems related to that condition, because the gene on her other X chromosome continues to function properly and "masks" the abnormal gene. However, males only inherit one copy of the information stored on the X chromosome. When a male inherits the gene for an X-linked recessive condition, he will experience the symptoms associated with that condition. The mutated or changed genes which cause FGS are located on the X chromosome and thus the full-blown disorder primarily affects males carrying the mutated or changed gene on their one X chromosome. When a condition is X-linked, the gene for the condition travels through the family on the X chromosome. In X-linked genetic conditions, the risk for a carrier female to have an affected son is 50%, while the risk to have a carrier daughter is also 50%. An affected male has a 100% chance of having carrier daughters and no chance to have an affected son.

Individuals inheriting the same mutated gene in the same family can have very different symptoms. For example, approximately 38% of individuals affected by FGS have anal anomalies, like a missing anal opening (imperforate anus), while mental retardation is present in 97% of individuals affected by FGS. The difference in physical findings within the same family is known as variable penetrance or intrafamilial variability.

Demographics

FG syndrome can appear in any ethnic population. FGS has been described in individuals of Japanese, American, European, African, and other ethnic background. FGS is not believed to be more common in one specific population.

Signs and symptoms

Individuals affected by FG syndrome can be affected by a variety of symptoms. Most affected individuals have signs of FGS such as mental retardation, low muscle tone and physical development, seizures, large heads, big foreheads, a front cowlick of hair, wide-spaced eyes, extra eye folds (short, palpebral fissures), constipation, and an outgoing, talkative personality. Other fairly common signs of FGS include anal abnormalities (imperforate anus), brain abnormalities (partial agenesis of the corpus callosum, hearing impairments, broad thumbs and big toes, small ears, fine/thinning hair, fused fingers, minor back bone abnormalities, cleft lip and palate , heart defects, and fetal fingertip pads.

Diagnosis

Diagnosis of FGS is usually made from physical examination by a medical geneticist. The physical examination looks for the combined characteristic features, low muscle tone, mental retardation, etc., of FGS.

Although mutations in specific genes that cause FGS have been found, molecular genetic testing (prenatal or diagnostic) is not yet available.

Treatment and management

FG syndrome (FGS) is a genetic disorder and does not have a specific therapy that removes, cures, or fixes all signs of the disorder.

Management and treatment for FGS mainly focuses on the treatment of specific symptoms. More specifically, individuals with incompletely formed anal openings and serious heart defects would need surgery to try to correct the problems. Individuals affected by FGS who have mental retardation benefit from special school and early intervention programs.

Prognosis

The prognosis of an individual affected by FG syndrome depends on the severity of the symptoms by which they are affected. For example, approximately one-third of individuals affected by FGS will die before two years of age due to the severity of heart defects and anal abnormalities.

Most individuals affected by FGS who do not have severe physical problems, such as serious heart defects and anal abnormalities, are still affected by mental retardation. Individuals affected by FGS who have mental retardation benefit from special schools and early intervention programs.

Resources

BOOKS

Smith, Raomayne, and Eunice Kennedy Shriver, eds. Children with Mental Retardation, A Parents' Guide. Bethesda, MD: Woodbine House, 1993.

Trainer, Marilyn, and Helen Featherstone. Differences in Common: Straight Talk on Mental Retardation, Down Syndrome, and Your Life. Bethesda, MD: Woodbine House, 1991.

PERIODICALS

FG Syndrome Family Alliance Print Newsletter FG Syndrome Family Alliance, subscribe by sending email to : FGSNewsl@aol.com.

ORGANIZATIONS

Arc (a National Organization on Mental Retardation). 1010 Wayne Ave., Suite 650, Silver Spring, MD 20910. (800) 433-5255. <http://www.thearclink.org>.

WEBSITES

The Family Village. <http://www.familyvillage.wisc.edu>.

FG Syndrome Family Alliance. FG Syndrome Homepage. <http://www.geocities.com/HotSprings/Spa/3687/>.

On-line Mendelian Inheritance of Man. <http://www3.ncbi.nlm.nih.gov/Omim/>.

Dawn A. Jacob, MS, CGC