Aarskog–Scott Syndrome

Aarskog–Scott syndrome (AAS) is a rare disorder inherited in an X-linked manner and is marked by short stature, facial abnormalities, and skeletal and genital anomalies. This condition primarily affects males, though females may exhibit mild features of the syndrome.

Signs and symptoms

Individuals with Aarskog–Scott syndrome often display distinctive facial features, such as widely spaced eyes (hypertelorism), a small nose, an elongated area between the nose and mouth (philtrum), and a widow's peak hairline. They often experience mild to moderate short stature during childhood, but their growth typically aligns with their peers during puberty. Common hand abnormalities in this syndrome 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 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).

Most males with Aarskog–Scott syndrome have a shawl scrotum, where the scrotum surrounds the penis rather than hanging below. Occasionally, they may have undescended testes (cryptorchidism) or a soft out-pouching around the belly-button (umbilical hernia) or in the lower abdomen (inguinal hernia).

The intellectual development of individuals with Aarskog–Scott syndrome varies significantly. Some may experience mild learning and behavioral challenges, while others have normal intelligence. In rare instances, severe intellectual disability has been noted.

Genetics

Mutations in the FGD1 gene are the sole known genetic cause of Aarskog-Scott syndrome. The FGD1 gene provides instructions for producing a protein that activates another protein called CDC42, which relays signals vital for various developmental processes before and after birth.

Mutations in the FGD1 gene result in a malfunctioning protein. These mutations disrupt CDC42 signaling, leading to the diverse abnormalities seen in individuals with Aarskog-Scott syndrome.

Approximately 20 percent of individuals with this disorder have identifiable mutations in the FGD1 gene. The cause of Aarskog-Scott syndrome in other affected individuals remains unknown.

Diagnosis

Genetic testing may be available for mutations in the FGDY1 gene. Genetic counseling is recommended for individuals or families who may carry this condition, as there are overlapping features with fetal alcohol syndrome.

Additional examinations or tests can assist with diagnosis. These may include:

• comprehensive family history

• performing a detailed physical examination to document morphological features

• testing for genetic defects in FGDY1

• x-rays to identify skeletal abnormalities

• echocardiogram to screen for heart abnormalities

• CT scan of the brain for cystic development

• X-ray of the teeth

• Ultrasound of the abdomen to identify undescended testes

Treatment

Like all genetic disorders, Aarskog–Scott syndrome cannot be cured, but various treatments are available to enhance the quality of life. Surgery may be necessary to correct some anomalies, and orthodontic treatment may be employed to address certain facial abnormalities. Trials of growth hormone have been effective in treating short stature associated with this disorder.

Prognosis

Some individuals may experience some cognitive delays, but children with this condition often possess good social skills. Some males may face fertility issues.