Aarskog-Scott syndrome is a rare genetic disorder affecting the development of several parts of the body. Also known as faciogenital dysplasia, the condition primarily impacts the formation of the face, limbs, and genitals. Its effects are seen most often in males, though females can sometimes present with mild features of the syndrome.
Genetic Causes and Inheritance
Aarskog-Scott syndrome results from a mutation in a specific gene known as FGD1. This gene provides instructions for making a protein that activates another protein, Cdc42, which is involved in signaling pathways for development before and after birth. The FGD1 protein plays a part in embryonic development, particularly in the formation of the skeleton.
The inheritance pattern for the condition is X-linked. The FGD1 gene is located on the X chromosome, one of the two sex chromosomes. Because males have only one X chromosome, a single altered copy of the gene is sufficient to cause the condition. Females, having two X chromosomes, would need mutations in both copies to be fully affected, which is unlikely.
The disorder is passed down from a mother who carries one copy of the mutated gene to her son. A female carrier of the mutated gene often shows no significant symptoms. She may, however, display very subtle features, such as widely spaced eyes or a widow’s peak hairline. In a number of cases, no mutation in the FGD1 gene is found, suggesting that other genes may also be involved.
Key Physical and Developmental Features
The syndrome’s characteristic physical traits can vary in severity among individuals. While most have normal intelligence, some may experience mild learning or behavioral differences in childhood.
Facial Features
Distinctive facial features can include widely spaced eyes, a small nose, and a long area between the nose and mouth. A V-shaped hairline, commonly called a widow’s peak, is another frequent characteristic. Other features may include drooping eyelids and a broad nasal bridge.
Skeletal and Limb Features
Skeletal development is also affected, resulting in short stature that may not become apparent until a child is between one and three years old. Hand and foot abnormalities are common, including short fingers and toes, webbing of the skin between digits, and a single crease across the palm. The fifth finger may also show a curve, a feature known as clinodactyly.
Genital Features
The development of the genitals is impacted, particularly in males. A common feature is the “shawl scrotum,” where the scrotal tissue surrounds the penis instead of hanging below it. Some males may also have undescended testicles or hernias in the lower abdomen or around the belly button.
The Diagnostic Process
Diagnosing Aarskog-Scott syndrome begins with a clinical examination, where a doctor will look for the characteristic physical features of the face, limbs, and genitals. The presence of several of these key traits raises the initial suspicion of the syndrome.
A detailed family medical history is also an important part of the diagnostic process. Identifying a pattern of the condition in the family, consistent with X-linked inheritance, can provide strong supporting evidence for a diagnosis. The doctor will inquire about similar features in male relatives on the mother’s side of the family.
While physical traits and family history are highly suggestive, a definitive diagnosis is achieved through molecular genetic testing. This test analyzes a blood sample to identify a disease-causing mutation in the FGD1 gene. A positive genetic test confirms the diagnosis, although a negative result does not completely rule it out, as other, yet-to-be-identified genes may also cause the syndrome.
Management of Symptoms
There is no cure for the underlying genetic cause of Aarskog-Scott syndrome, so treatment focuses on managing the specific symptoms of each individual. This supportive care often involves a team of specialists to address the various health issues that may arise.
Interventions are tailored to the person’s needs. For example, surgical procedures may be performed to correct genital anomalies like undescended testicles or to repair hernias. Orthodontic care is often necessary to address dental abnormalities that may occur. In cases where short stature is a significant concern, growth hormone therapy may be considered to promote growth during childhood.
With appropriate and timely management of symptoms, the overall prognosis for individuals with Aarskog-Scott syndrome is generally positive. Most affected people can expect to have a normal life expectancy. Regular monitoring and supportive care enable them to manage the challenges associated with the condition.