FG syndrome

Overview

FG syndrome, also known as Opitz-Kaveggia syndrome, is a rare genetic disorder that primarily affects males and is characterized by intellectual disability, low muscle tone (hypotonia), distinctive facial features, and abnormalities of the central nervous system. The syndrome can also include behavioral issues, gastrointestinal problems such as constipation, and a high-arched palate. The term “FG” comes from the initials of the surnames of the first documented families affected by the condition.

Causes

FG syndrome is most commonly caused by mutations in the MED12 gene located on the X chromosome (Xq13). This gene is involved in regulating gene expression during development, particularly in the brain. Because the condition is inherited in an X-linked recessive manner, it primarily affects males, while females are typically carriers with milder or no symptoms. Rarely, mutations in other genes such as FLNA or PHF6 may also be associated with FG-like phenotypes.

Symptoms

The presentation of FG syndrome can vary, but common signs and symptoms include:

Neurological and Developmental

• Intellectual disability (mild to severe)

• Delayed developmental milestones

• Hypotonia in infancy

• Hydrocephalus or enlarged ventricles in some cases

Behavioral Features

• Hyperactivity

• Social and friendly personality

• Short attention span and impulsivity

Facial and Physical Characteristics

• Long narrow face with a prominent forehead

• Wide-set eyes (hypertelorism)

• Small, simple ears

• Downturned mouth or thin upper lip

• High-arched or cleft palate

Other Possible Features

• Constipation and other gastrointestinal issues

• Cardiac anomalies

• Genitourinary abnormalities (e.g., undescended testes)

• Seizures in some cases

Diagnosis

Diagnosis of FG syndrome is based on clinical evaluation, family history, and confirmatory genetic testing. Key steps include:

• Clinical assessment: Identification of characteristic physical, developmental, and behavioral features.

• Genetic testing: Detection of a mutation in the MED12 gene confirms the diagnosis.

• Imaging studies: Brain MRI may show structural abnormalities such as agenesis of the corpus callosum or ventriculomegaly.

• Family history: Evaluation of potential carrier status in mothers and identification of other affected relatives.

Treatment

There is no cure for FG syndrome, so treatment is supportive and based on the individual's specific needs. A multidisciplinary approach is often required and may include:

• Early intervention programs: Physical, occupational, and speech therapy to address developmental delays.

• Educational support: Special education tailored to the child’s learning abilities.

• Behavioral therapy: To manage hyperactivity, attention difficulties, and impulsive behavior.

• Medical management: Treatment for constipation, seizures, cardiac defects, or other associated health issues.

• Genetic counseling: For families to understand the inheritance pattern and recurrence risk in future pregnancies.

Prognosis

The prognosis for individuals with FG syndrome varies depending on the severity of symptoms and associated medical conditions. Many affected individuals can lead fulfilling lives with appropriate support and therapies. Cognitive and behavioral challenges may persist throughout life, but early intervention can significantly improve outcomes. With proper medical care and educational support, many individuals achieve a degree of independence in adulthood.