Simpson-Golabi-Behmel syndrome (SGBS) is a rare genetic disorder characterized by excessive growth before and after birth. This condition belongs to a group of disorders known as overgrowth syndromes, which involve accelerated growth in various body parts. SGBS primarily affects males, leading to a distinctive set of physical characteristics and potential health considerations.
Genetic Causes and Inheritance
The most common cause of Simpson-Golabi-Behmel syndrome involves a mutation in the GPC3 gene, located on the X chromosome. This gene provides instructions for making glypican-3, a protein that helps regulate cell growth and division. When the GPC3 gene is altered, the protein may not function correctly, leading to the uncontrolled growth seen in affected individuals.
SGBS follows an X-linked inheritance pattern, meaning the mutated gene resides on the X chromosome. Males have one X and one Y chromosome, so a single altered GPC3 gene on their X chromosome is sufficient to cause the syndrome. Females, possessing two X chromosomes, are typically carriers of the condition. They usually have one normal GPC3 gene on their other X chromosome, which often compensates for the mutated one, resulting in no symptoms or much milder features.
A mother who is a carrier has a 50% chance with each pregnancy of passing the mutated X chromosome to her child. If she passes it to a son, he will develop SGBS. If she passes it to a daughter, the daughter will be a carrier like herself. In rare instances, mutations in other genes, such as GPC4, have also been associated with SGBS, though GPC3 remains the primary genetic cause identified.
Physical and Developmental Characteristics
Individuals with Simpson-Golabi-Behmel syndrome typically exhibit significant overgrowth, evident even before birth with increased fetal size and birth weight. This accelerated growth continues throughout childhood, leading to a large overall body size. Their heads are also notably large, a condition known as macrocephaly, with a prominent forehead being a common feature.
Distinctive facial characteristics are often present, including a coarse facial appearance, wide-set eyes (hypertelorism), and a broad nasal bridge. A large mouth with a prominent tongue (macroglossia) is frequently observed, which can sometimes affect feeding or speech. Skeletal abnormalities, such as extra fingers or toes (polydactyly) or fused fingers or toes (syndactyly), and anomalies of the ribs or spine can also occur. Some individuals may present with supernumerary nipples, and internal organ involvement can include anomalies affecting the heart or kidneys. The spectrum of intellectual development varies widely, ranging from normal cognitive function to mild or severe intellectual disability.
Associated Health Risks
Individuals with Simpson-Golabi-Behmel syndrome have an increased susceptibility to developing certain types of embryonal tumors during childhood. The heightened chance of tumor formation is particularly relevant in the first few years of life. The most frequently observed tumors are Wilms tumor, which is a type of kidney cancer, and hepatoblastoma, a form of liver cancer. While these tumors are more common in children with SGBS than in the general population, it is important to note that not every child with the syndrome will develop a tumor. The risk is considered highest during the preschool years, gradually decreasing as the child gets older.
Diagnosis and Management
Diagnosis of Simpson-Golabi-Behmel syndrome typically begins with a clinical evaluation by a medical geneticist or pediatrician, recognizing the characteristic physical features. Molecular genetic testing is then performed to confirm the diagnosis, usually by analyzing a blood sample to identify a GPC3 gene mutation. Since there is no cure for SGBS, management focuses on addressing specific symptoms and monitoring for potential complications. A multidisciplinary team, including pediatricians, geneticists, cardiologists, nephrologists, and oncologists, is generally involved. Regular surveillance protocols are put in place to detect potential tumors early, typically involving periodic abdominal ultrasounds and blood tests to measure alpha-fetoprotein (AFP) levels.