Which are the causes of Simpson-Golabi-Behmel syndrome?

Simpson-Golabi-Behmel syndrome (SGBS) is a rare genetic disorder that primarily affects males. It is characterized by a wide range of physical and developmental abnormalities. The syndrome was first described in the 1970s by Simpson, Golabi, and Behmel, hence the name.

The causes of Simpson-Golabi-Behmel syndrome are attributed to mutations in the GPC3 gene, which is located on the X chromosome. This gene provides instructions for producing a protein called glypican 3. Glypican 3 is involved in regulating cell growth and division during embryonic development. Mutations in the GPC3 gene lead to a deficiency or dysfunction of glypican 3, resulting in the characteristic features of SGBS.

SGBS is an X-linked recessive disorder, meaning that the mutated gene is located on the X chromosome. Males have one X and one Y chromosome, while females have two X chromosomes. Since males have only one copy of the X chromosome, a single mutation in the GPC3 gene is sufficient to cause the syndrome. In females, who have two X chromosomes, a mutation would need to be present on both copies of the gene to manifest the disorder. However, females with a single mutated copy of the GPC3 gene may still exhibit some features of SGBS, albeit typically milder in severity.

Most cases of Simpson-Golabi-Behmel syndrome are not inherited from an affected parent but occur as spontaneous mutations. These mutations can occur during the formation of sperm or egg cells or early in embryonic development. However, in some cases, the syndrome can be inherited from a carrier mother who has a single mutated copy of the GPC3 gene. Carrier females have a 50% chance of passing on the mutated gene to their children, regardless of the child's gender.

The symptoms and characteristics of Simpson-Golabi-Behmel syndrome can vary widely among affected individuals. However, there are several common features that are often observed. These include:

• Overgrowth: Individuals with SGBS tend to have increased birth weight and height compared to average individuals. This overgrowth continues throughout childhood and can result in a larger overall body size.


• Facial abnormalities: Facial features associated with SGBS include a broad nasal bridge, wide-spaced eyes, a prominent forehead, and a wide mouth with a thick upper lip.


• Organ abnormalities: SGBS can affect various organs, including the heart, kidneys, liver, and gastrointestinal system. These abnormalities can lead to functional impairments and may require medical intervention.


• Intellectual disability: Many individuals with SGBS have some degree of intellectual disability, ranging from mild to severe. Developmental delays and learning difficulties are also common.


• Skeletal abnormalities: Skeletal anomalies such as extra fingers or toes (polydactyly), joint abnormalities, and spinal defects may be present in individuals with SGBS.


• Other features: Additional features of SGBS can include hernias, hearing loss, dental abnormalities, and genitourinary anomalies.

Diagnosis of Simpson-Golabi-Behmel syndrome is typically based on clinical evaluation and genetic testing. A thorough physical examination, including a detailed family history, can help identify characteristic features of the syndrome. Genetic testing can confirm the presence of mutations in the GPC3 gene.

Management and treatment of Simpson-Golabi-Behmel syndrome involve a multidisciplinary approach. Since the syndrome affects multiple organ systems, a team of specialists, including geneticists, pediatricians, cardiologists, orthopedic surgeons, and developmental specialists, may be involved in the care of affected individuals.

Treatment is focused on addressing the specific symptoms and complications associated with SGBS. This may include surgical interventions for organ abnormalities, physical and occupational therapy for developmental delays, and educational support for learning difficulties. Regular monitoring and follow-up are essential to manage the ongoing medical needs of individuals with SGBS.

In conclusion, Simpson-Golabi-Behmel syndrome is a rare genetic disorder caused by mutations in the GPC3 gene. It primarily affects males and is characterized by a wide range of physical and developmental abnormalities. The syndrome is typically not inherited from affected parents but occurs as spontaneous mutations. Diagnosis is based on clinical evaluation and genetic testing. Management involves a multidisciplinary approach to address the specific symptoms and complications associated with SGBS. Ongoing monitoring and support are crucial for individuals with this syndrome.