Aarskog–Scott syndrome

Aarskog–Scott syndrome (AAS) is a rare disease

People with Aarskog–Scott syndrome often have distinctive facial features, such as widely spaced eyes (hypertelorism), a small nose, a long area between the nose and mouth (philtrum), and a widow's peak hairline. They frequently have mild to moderate short stature during childhood, but their growth usually catches up with that of their peers during puberty. Hand abnormalities are common in this syndrome and include short fingers (brachydactyly), curved pinky fingers (fifth finger clinodactyly), webbing of the skin between some fingers (cutaneous syndactyly), and a single crease across the palm. Other abnormalities in people with Aarskog–Scott syndrome include heart defects and a split in the upper lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate).^[3]

Most males with Aarskog–Scott syndrome have a shawl scrotum, in which the scrotum surrounds the penis instead of hanging below. Less often, they have undescended testes (cryptorchidism) or a soft out-pouching around the belly-button (umbilical hernia) or in the lower abdomen (inguinal hernia).^[3]

The intellectual development of people with Aarskog–Scott syndrome varies widely. Some may have mild learning and behavior problems, while others have normal intelligence. In rare cases, severe intellectual disability has been reported.^[3]

Genetics

Mutations in the FGD1 gene are the only known genetic cause of Aarskog-Scott syndrome. The FGD1 gene provides instructions for making a protein that turns on (activates) another protein called Cdc42, which transmits signals that are important for various aspects of development before and after birth.^[3]

Mutations in the FGD1 gene lead to the production of an abnormally functioning protein. These mutations disrupt Cdc42 signaling, leading to the wide variety of abnormalities that occur in people with Aarskog-Scott syndrome.^[3]

Only about 20 percent of people with this disorder have identifiable mutations in the FGD1 gene. The cause of Aarskog-Scott syndrome in other affected individuals is unknown.^[3]

Pathophysiology

The Aarskog–Scott syndrome is due to mutation in the

Within the developing mouse skeleton, FGD1 protein is expressed in precartilaginous mesenchymal condensations, the perichondrium and periosteum, proliferating chondrocytes, and osteoblasts. These results suggest that FGD1 signaling may play a role in the biology of several different skeletal cell types including mesenchymal prechondrocytes, chondrocytes, and osteoblasts. The characterization of the spatiotemporal pattern of FGD1 expression in mouse embryos has provided important clues to the understanding of the pathogenesis of Aarskog–Scott syndrome.^{[citation needed]}

It appears likely that the primary defect in Aarskog–Scott syndrome is an abnormality of FGD1/Cdc42 signaling resulting in anomalous

• detailed family history
• conducting a detailed physical examination to document morphological features
• testing for genetic defect in FGDY1
• x-rays can identify skeletal abnormalities
• echo cardiogram can screen for heart abnormalities
• CT scan of the brain for cystic development
• X-ray of the teeth
• Ultrasound of abdomen to identify undescended testis[6]

Treatment

Similar to all genetic diseases Aarskog–Scott syndrome cannot be cured, although numerous treatments exist to increase the quality of life.^[6]

Some people may have some mental slowness, but children with this condition often have good social skills. Some males may have problems with fertility.[4]

History

The syndrome is named for Dagfinn Aarskog, a Norwegian pediatrician and human geneticist who first described it in 1970,^[8] and for Charles I. Scott, Jr., an American medical geneticist who independently described the syndrome in 1971.^[9]

References