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Simpson-Golabi-Behmel syndrome


Other Names for this Disease
  • Bulldog syndrome
  • Dysplasia gigantism syndrome, X-linked
  • Golabi-Rosen syndrome
  • SGBS
  • SGBS1
More Names
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Your Question

My partner is a carrier for Simpson-Golabi-Behmel syndrome and her son was diagnosed with this rare condition. Is there information regarding prognosis or life expectancy for individuals with this syndrome? What are the potential long term effects on cardiac function? Could any heart abnormalities be corrected? How does the genetic mutation cause this condition, and should we expect other body areas to be affected? Also, my partner gets supraventricular tachycardia including atrial fibrillation. Can carriers of SGBS manifest some signs or symptoms of the condition? Can any type of procedure or intervention help my partner's heart issues?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What is Simpson-Golabi-Behmel syndrome?

Simpson-Golabi-Behmel syndrome (SGBS) is a condition that affects many parts of the body and occurs primarily in males. It is an overgrowth syndrome, which means that affected individuals have macrosomia and continue to grow and gain weight at an unusual rate. The severity varies from very mild forms in carrier females to infantile lethal forms in affected males.[1] Individuals typically have distinctive facial features including hypertelorism, macrostomia, macroglossia, a broad nose with an upturned tip, and palatal abnormalities.[2] Other, variable findings include extra nipples, diastasis recti, umbilical hernia, congenital heart defects, renal defects, gastrointestinal anomalies, skeletal anomalies, hand anomalies, genitourinary abnormalities, and hepatosplenomegaly.[3][2] Some people with the condition have mild to severe intellectual disability. About 10 percent of people with SGBS develop tumors in early childhood, including Wilms tumor and neuroblastoma. Some cases of SGBS are caused by mutations in the GPC3 gene and in other cases, the cause is unknown.[2] It is inherited in an X-linked recessive manner.[4]
Last updated: 2/15/2011

What is the prognosis and life expectancy for individuals with Simpson-Golabi-Behmel syndrome?

The spectrum of signs and symptoms associated with Simpson-Golabi-Behmel syndrome is very broad, varying from very mild forms in carrier females to infantile lethal forms in affected males. As many as 50% of affected males die in the newborn period, although the causes of this high mortality remain unknown;[1] it has been suggested that it is probably related to cardiac abnornalities.[4] People with milder cases often live into adulthood.[2] Because of the varying degrees of manifestations and severity associated with the condition, prediction of prognosis and life expectancy most likely varies on an individual basis.
Last updated: 5/27/2011

What are the long term effects of this disorder on cardiac function?

Some authors have concluded that cardiac abnormalities of any type are common in Simpson-Golabi-Behmel syndrome (SGBS), and that they occur in almost one half of cases, with cardiovascular malformations (congenital heart defects) seen in one-third of cases.[5] Therefore, it is likely that the effects of SGBS on cardiac function are variable and may depend on how severely affected an individual is, as well as the nature of the cardiac abnormality that an individual has or may be more likely to develop. It has been recommended that the heart function should be watched closely in individuals with SGBS, because it can be a cause of early death.[1] It has also been recommended that individuals with congenital heart disease (either corrected or uncorrected) undergo anticoagulation (use of blood thinners) to prevent thromboembolic events (blood clots) and antibiotic prophylaxis to prevent bacterial endocarditis.[6]

Septal defects (abnormal openings between 2 chambers of the heart) seem to be common, and pulmonary stenosis, aortic coarctation, transposition of the great vessels, and patent ductus arteriosus or patent foramen ovale have been reported. Conduction defects and arrhythmias (irregular heartbeats) have also been described, as well as cardiomyopathy.[6][1] One author suggested that cardiac arrhythmias may be a major component of SGBS and can be responsible for death in early infancy and perhaps for cardiac arrest in adults.[5] Another article discussed a 44-year-old man who had an acute internal carotid artery dissection; the authors suggested that the overgrowth involved in SGBS may have caused an increase in the length of the carotid, leading to a greater risk of dissection.[5]

Individuals interested in learning about their own cardiac conditions or risks should speak with their health care provider or a cardiologist.
Last updated: 5/27/2011

Can heart abnormalities in an individual with Simpson-Golabi-Behmel syndrome be corrected?

A large variety of cardiac abnormalities have been reported in individuals with SGBS. Whether or not a heart abnormality can be corrected depends on the type and severity of the heart abnormality that an individual has.  For example, some congenital heart defects, such as ventricular septal defects (VSD), can range from mild to severe; a small defect may not require treatment while a large defect, which can cause heart failure, may require medications and surgery to close the hole. Other cardiac abnormalities which develop later in life may require surveillance in order to identify risks and problems as early as possible. Individuals interested in information about specific risks and cardiac abnormalities, including possible treatment options, should speak with their health care provider or cardiologist.
Last updated: 2/15/2011

How does a mutation in the GPC3 gene cause the signs and symptoms of Simpson-Golabi-Behmel syndrome?

Mutations (changes) in the GPC3 gene are responsible for some cases of Simpson-Golabi-Behmel syndrome (SGBS). This gene provides instructions for making a protein called glypican 3, which is involved in the regulation of cell growth and division (cell proliferation). Researchers believe that the functioning GPC3 protein can cause certain cells to self-destruct (undergo apoptosis) when they are no longer needed, which can help establish the body's shape. GPC3 mutations can delete part or all of the gene, or alter the structure of glypican 3 protein. These mutations prevent the protein from performing its usual functions, which may contribute to an increased rate of cell growth and cell division, starting before birth. It is unclear, however, how a shortage of functional glypican 3 causes overgrowth of the entire body and the other abnormalities characteristic of SGBS.[2] The gene appears to be expressed in a number of tissues, including the lung, liver, and kidney.[1] Researchers also believe that in some cell types, when the gene and protein are working correctly, glypican 3 may act as a tumor suppressor, which is a protein that prevents cells from growing and dividing in an uncontrolled way to form a cancerous tumor.[7]
Last updated: 2/15/2011

Can a female carrier for Simpson-Golabi-Behmel syndrome manifest signs or symptoms of the condition?

Yes, it is possible for a female carrier for SGBS to manifest signs and symptoms of the condition. SGBS is inherited in an X-linked manner. This means that the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome and one Y chromosome), one altered copy of the gene in each cell is sufficient to cause the condition, because they do not have another X chromosome with a working copy. Because females have two copies of the X chromosome, one altered copy of the gene in each cell usually leads to less severe symptoms in females than in males, or may cause no symptoms at all.[2]

One of the reasons that carrier females may show varying degrees of symptoms is called X-inactivation. This involves randomly "switching off" most of one of the X chromosomes in women, which ensures that women and men have generally the same number of X chromosome genes working in the cell. If the normal, random process of switching off one of the X chromosomes has been skewed strongly towards switching off the X chromosome carrying the working copy of the gene, more cells in the woman's body would contain an active X chromosome with the mutated copy of the gene. This would lead to less of the working gene product being available, so the woman will show the effects of the mutated gene, though usually less severely than in men.[8]

It has been reported that some females who have one altered copy of the GPC3 gene have distinctive facial features including an upturned nose, a wide mouth, and a prominent chin. Their fingernails may be malformed and they can have extra nipples. Skeletal abnormalities, including extra spinal bones (vertebrae), have also been reported in affected females.[2] Penetrance (the proportion of individuals with a mutation who manifest signs or symptoms of the condition) in carrier females is unknown.[6]
Last updated: 5/31/2011

How might supraventricular tachycardia be treated?

In most people, supraventricular arrhythmias are not dangerous. Mild arrhythmias, such as isolated premature beats, may require no treatment. A few people, however, may have arrhythmias that become dangerous and require immediate, perhaps prolonged, treatment. Treatment for supraventricular tachycardia usually focuses on decreasing the heart rate and breaking up the electrical circuits made by the abnormal conducting pathways. It includes stopping the acute episode and preventing any new ones. One of the most important considerations in treating an acute episode of supraventricular tachycardia is how severely the heart function has been affected. If an individual has low blood pressure, chest pain, or a failing heart with tachycardia, the condition may be considered unstable. Such cases may cause serious danger and require immediate treatment. Health care providers typically devise treatment that meets the specific cause of an individual's supraventricular tachycardia.  Treatment options (when being treated by a health care provider) may include vagal maneuvers, carotid massage, medications, use of a pacemaker, or surgery.[9]

The materials provided are for informational or educational purposes only and are not intended as a substitute for professional medical care, advice, diagnosis, or treatment. Individuals seeking treatment options for supraventricular tachycardia or another cardiac abnormality should speak with their health care provider or cardiologist for personalized, expert advice.
Last updated: 2/15/2011

References