Simpson-Golabi-Behmel syndrome
Simpson-Golabi-Behmel syndrome is an X-linked overgrowth condition characterized by distinctive facial features, skeletal abnormalities, and an increased risk of childhood tumors.
Overview
Simpson-Golabi-Behmel syndrome is a condition that affects many parts of the body and occurs primarily in males. It is classified as an overgrowth syndrome, meaning affected infants are considerably larger than normal at birth (macrosomia) and continue to grow and gain weight at an unusual rate. While symptoms vary widely, individuals with mild cases often live into adulthood.
Symptoms
The physical characteristics of the syndrome are diverse and can include:
- Distinctive facial features: Widely spaced eyes, an unusually large mouth, a large tongue that may have a groove down the middle, a broad nose with an upturned tip, and abnormalities of the palate. In older children and adults, these features are often described as coarse.
- Chest and abdominal abnormalities: Extra nipples, diastasis recti (an abnormal opening in the abdominal muscle), umbilical hernia, or a hole in the diaphragm that may crowd the heart and lungs.
- Organ and skeletal issues: Heart defects, malformed or abnormally large kidneys, an enlarged liver and spleen (hepatosplenomegaly), and various skeletal abnormalities.
- Developmental impact: Potential abnormalities affecting the development of the skeleton, kidneys, and genitalia. Intellectual disability ranging from mild to severe may occur, though some individuals have normal intelligence.
- Tumor risk: Approximately 10 percent of affected individuals develop cancerous or noncancerous tumors in early childhood, most commonly Wilms tumor (a rare form of kidney cancer) or neuroblastoma.
Causes & Risk Factors
The most common cause is a mutation in the GPC3 gene, which provides instructions for making the protein glypican 3. This protein inhibits the hedgehog signaling pathway, which is critical for cell growth, specialization, and embryonic patterning. Mutations prevent this inhibition, leading to overactive signaling and increased cell proliferation.
Some individuals do not have an identified GPC3 mutation, and the cause remains unknown in these cases. A more severe, distinct disorder previously designated as Simpson-Golabi-Behmel syndrome type 2 (SGBS2) is now considered a separate condition.
Inheritance
This condition is inherited in an X-linked pattern. Because males have only one X chromosome, one altered copy of the gene is sufficient to cause the syndrome. Females have two X chromosomes; therefore, one altered copy usually results in less severe health problems or no symptoms at all, though some females may exhibit distinctive facial features, malformed fingernails, extra nipples, or skeletal abnormalities.