FG Syndrome – Causes, Symptoms & Treatment


FG syndrome is an X-linked abnormality. Those affected suffer from defective vitamin D receptors and, as a result, complex symptoms such as developmental delay, muscle weakness, strabismus and sensorineural hearing loss. Treatment is symptomatic.

What is FG Syndrome?

Chromosomal aberrations are also known as chromosomal abnormalities. They are structural or numerical changes in chromosomes in an organism or a specific cell. Chromosomal aberrations are therefore major changes within the genetic material that can trigger serious clinical pictures.

A structural chromosomal abnormality is the FG syndrome, which is also referred to in the literature as Opitz-Kaveggia syndrome or Keller syndrome . The disease is a serious and rare condition that is caused by abnormalities in the X chromosome and results in developmental delays in addition to physical abnormalities.

The disease was first described in 1974. John Marius Opitz and Elisabeth Kaveggia are considered the first to describe it. The term FG syndrome has its roots in an acute case of the syndrome. The letters F and G are the surname initials of two sisters who gave birth to multiple children with the syndrome.

According to current knowledge, there are allelic connections between FG syndrome and Lujan-Fryns syndrome . The prevalence for FG syndrome is estimated at 1 case in 500 newborns. Heart defects and defects in the limbs cannot be ruled out either.


FG syndrome is caused by mutations in the MED12 gene, better known as mediator complex subunit 12. The gene is located on gene locus 13.1 of the X chromosome and carries 44 exons. The unit encodes in the DNA for a subunit of the mediator complex, which is also known as mediator or thyroid hormone receptor-associated protein.

Other names are TRAP or thyroid hormone receptor-associated protein, vitamin D receptor interacting protein, and DRIP and vitamin D receptor-interacting protein. The proteinergic gene product consists of 28 subunits.

If there is a structural anomaly in the corresponding chromosome, the composition of the protein changes structurally so that the complex can no longer fulfill its physiologically intended functions and a defective vitamin D receptor is formed.

There are different sub-forms of the FG syndrome, which depend on the exact gene locus of the chromosomal abnormality. In addition to the Xq13 locus, abnormalities have been documented in FLNA Xq28, Xp22.3, CASK Xp11.4-p11.3 and Xq22.3. Based on the family disposition observed, an x-chromosomal hereditary basis is obvious.

Symptoms, Ailments & Signs

Patients with FG syndrome have a key symptom of severe mental retardation . In most cases there are also multiple personality changes. In almost all cases, a strong tendency towards hyperactivity was observed. Accompanying symptoms can be anomalies in the facial area.

The facial features of the patients, for example, often appear lifeless and unfriendly. In many cases, there is low muscle tone throughout the body. The corners of the mouth hang down accordingly and motor skills can be limited. In some cases, a permanently open mouth was observed, which is also due to the reduced muscle tone. Gastrointestinal symptoms have also been documented.

Chronic constipation is one of the most important symptoms in this context. In individual cases, foramen parietale permagnum (FPP) was found in the patients . This is a rare disorder of cranial development associated with bony defects of the parietal bone and significant enlargement of the parietal foramina.

The respiratory tract of many patients is also susceptible to infections. Additionally, cleft palate , cleft larynx, strabismus , hernia , hypospadias , hydrocele , sleep apnea , and sensorineural hearing loss, as well as recurrent otitis or reflux can be signs of FG syndrome.

Diagnosis & History

The first suspected diagnosis of FG syndrome is made in infancy or early childhood. In most cases, clinical symptoms such as reduced muscle tone, the permanently open mouth and chronic constipation are the first indications of the syndrome. The doctor provides evidence of the reduced muscle tone through neuroelectrical examinations.

Molecular genetic methods are used to confirm the diagnosis, which provide evidence of the causative chromosomal abnormality. In terms of differential diagnosis, slight variants of GBBB syndrome, Atkin-Flaitz syndrome, fragile X syndrome, Keipert syndrome, naso-digito-acoustic syndrome, and Say-Meyer syndrome must be distinguished.

The same is true for Donnai-Barrow syndrome, Sotos syndrome , and C syndrome . Pelizaeus-Merzbacher disease , Dubowitz syndrome and Renpenning syndrome are also possible differential diagnoses. A suspicion can be raised before birth in the malformation ultrasound. Patients with FG syndrome have an unfavorable prognosis. Many of those affected die during childhood. After the critical childhood phase, only a few of the patients die.

When should you go to the doctor?

Parents who notice birth defects, signs of chronic constipation, and other signs of FG syndrome in their child should see their pediatrician. The X-linked abnormality is a serious condition that definitely needs to be diagnosed and treated. Therefore, unusual complaints, external abnormalities and other symptoms should be clarified by a doctor. If serious complications arise, the best-case scenario is that the medical emergency services will be contacted or the child should be taken to a hospital immediately.

Patients suffering from FG syndrome require close monitoring and regular evaluation. Depending on the severity of the abnormality, treatment may need to be performed by multiple doctors. In the case of hearing problems, for example, an audiologist must be consulted, while an ophthalmologist or optician is the right person to contact if you have vision problems. The doctor in charge can best answer which doctors are to be called in. In most cases, he will also recommend therapeutic counseling to the parents and initiate the necessary support for the child.

Treatment & Therapy

A causal treatment for the FG syndrome is not yet available. Because it is a genetic disease, advances in gene therapy over the next few decades may open up causal treatment options. At the present time, patients with the syndrome are treated purely symptomatically.

The treatment of the life-threatening symptoms is the focus of the treatment measures. Above all, possible heart defects must be corrected invasively. Surgical treatments are also available for cleft palate, cleft larynx, reflux, hernias, strabismus, hypospadias, and hydrocele.

A feeding tube may be needed to secure nutrition. CPAP ventilation is used for sleep apnea. Sensorineural hearing loss is treated with cochlear implants . The doctor treats recurrent otitis with tubes to equalize the pressure.

Growth hormone therapy can counteract severe growth disorders. On the supportive therapeutic side, parents of affected children receive psychological support. Mental retardation is counteracted therapeutically by means of early support.

Outlook & Forecast

FG syndrome offers an unfavorable prognosis. The sick children often die during childhood. If the first years of life are survived, there is a high chance of survival. However, the symptoms significantly impair the well-being and general quality of life of those affected. Psychological treatment must therefore always be initiated during therapy. This can at least improve mental well-being.

Nevertheless, FG syndrome is a serious condition that places a great deal of strain on those affected. Mental retardation in particular has a negative effect on health, as it is associated with numerous neurological complaints. Accompanying symptoms such as constipation or foramen parietale permagnum can lead to further complications over the course of life, from which the patient may die.

Life expectancy is reduced and most of those affected die either in childhood or between the ages of 40 and 50. The limited ability to move can lead to being bedridden, being overweight and many other secondary complaints and long-term consequences that mean a further deterioration in the state of health of those affected. Early treatment can relieve symptoms and allow patients to lead relatively normal lives in a care facility.


So far, the FG syndrome can only be prevented by genetic counseling in family planning and, if necessary, fine ultrasound during pregnancy. The decision not to have a child is considered the most effective and so far only preventive measure if there is a corresponding family history.


In most cases, the options for aftercare in FG syndrome are severely limited. Since this is a genetic disease, it cannot be completely and causally treated. In order to prevent the FG syndrome from being passed on to children, genetic counseling should be carried out if you wish to have children. Self-healing cannot occur with this disease.

Most of those affected are dependent on surgical interventions to alleviate the symptoms. The patient should rest after such an operation and not engage in physical activity. In general, physical exertion or other stressful activities should be avoided.

Furthermore, those affected are often dependent on taking hormones that are intended to promote the growth of the patient. It is important to ensure that these hormones are taken correctly and, above all, regularly, taking into account possible side effects or interactions.

A doctor should therefore always be consulted if anything is unclear. Above all, parents must ensure that their children take their medication correctly. Since the FG syndrome can also often lead to psychological problems in the parents or relatives, they should also consult a psychologist.

You can do that yourself

Self-help options for FG syndrome are limited. Those affected are dependent on treatment by a doctor in order to limit the symptoms.

As children suffer from increased disability, they need strong support and encouragement in their lives. Above all, this must be done by their own parents and their relatives. This can minimize further complications in adulthood. Hyperactivity can also be treated with special training.

Since many patients also suffer from visual problems, visual aids should be worn from a young age. This can prevent further deterioration in vision. Reflux disease should also be diagnosed and treated early on in order to avoid a possible ulcer or tumor disease.

However, parents often need psychological support as well. This can take place through a psychologist or through discussions with other affected persons. Regular intake of growth hormones can also reduce growth and development disorders. FG syndrome cannot be directly prevented. However, prenatal examinations can indicate the syndrome at an early stage.

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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.