What are the Causes of Aarskog Syndrome?

Understanding Aarskog Syndrome: Causes, Genetics & Diagnosis

Aarskog-Scott syndrome is a genetic disorder that impacts multiple body systems, most notably the craniofacial structures, extremities, and the genitourinary tract. Although it predominantly affects males, females may exhibit subtler manifestations of the condition. Understanding the causes of this medical condition can aid in early detection, which in turn can improve treatment outcomes.

Read on to learn about the various causes of Aarskog syndrome, its treatment options, and diagnostic methods.

What are the Different Causes That Lead to Aarskog Syndrome?

Aarskog syndrome is primarily caused by mutations in a specific gene located on the X chromosome, making it an X-linked recessive disorder. Humans typically have 23 pairs of chromosomes, and the final pair, which is known as sex chromosomes, determines a person’s biological sex. Males have one X and one Y chromosome (XY), while females have two X chromosomes (XX).

Since the disorder is X-linked and recessive, its effects differ between males and females. Males with just one X chromosome are more vulnerable to this disorder. If the mutated gene is present on the only X chromosome, the individual is likely to develop the syndrome due to the absence of a second X chromosome to counterbalance the defect.

In females, the presence of a healthy X chromosome typically compensates for the effects of the mutated gene. As a result, most females become carriers without showing symptoms of the syndrome.

1. Case 1: Carrier Mother and Normal Father : When the mother is a carrier (XX) and the father is unaffected (XY), their children have a 50% chance of inheriting the mutated gene. A daughter who inherits the mutation becomes a carrier like her mother, while a son who inherits it will develop Aarskog syndrome because he lacks a second X chromosome to counter the mutation.
2. Case 2: Affected Father and Normal Mother : When the mother is unaffected (XX) and the father has the disorder (XY), daughters have a 100% chance of becoming carriers (XX) making them obligate carriers, but sons will inherit the father’s Y chromosome and remain unaffected (XY). Therefore, boys in this scenario are not at risk of the syndrome. 
3. Case 3: Carrier Mother and Affected Father : If the mother is a carrier (XX) and the father is affected (XY), children have more varied outcomes. Daughters have a 50% chance of being carriers (XX) and a 50% chance of being affected (XX). Sons face a 50% risk of inheriting the disorder (XY) or being completely unaffected (XY).

How is Aarskog Syndrome Treated?

The following approaches are commonly used for treating individuals with Aarskog syndrome:

1. Comprehensive, Team-Based Care : Managing Aarskog syndrome typically requires a coordinated, multidisciplinary approach. A team of healthcare professionals, such as orthopaedic surgeons, geneticists, paediatricians, urologists, and speech therapists, works together to create a treatment plan tailored to the individual’s specific symptoms and developmental needs.
2. Surgical Treatments : Surgery may be needed to correct certain physical abnormalities. Procedures might address issues such as undescended testicles, inguinal hernias, or structural problems in the hands and fingers. Orthopaedic surgeries can also be considered for musculoskeletal concerns.
3. Speech and Language Support : Children with Aarskog syndrome often experience delays in speech and language development. Speech therapy plays a key role in helping them improve articulation, language skills, and overall communication abilities.
4. Supportive Therapies : A range of therapies can help enhance daily functioning. Physical therapy may be used to strengthen muscles and support joint mobility, while occupational therapy can assist with fine motor skills. Educational interventions may also be necessary to address learning difficulties or developmental delays.
5. Genetic Counselling : Families affected by Aarskog syndrome are encouraged to seek genetic counselling. This service offers valuable insights into how the condition is inherited, the likelihood of recurrence in future pregnancies, and options for family planning.
6. Ongoing Monitoring and Care : Regular follow-up appointments are important, as the symptoms and their severity can vary. Consistent monitoring of growth, development, and any new medical concerns allows healthcare providers to adjust treatment plans as needed and ensure timely interventions.

How to Diagnose Aarskog Syndrome?

The following are the different ways to diagnose Aarskog syndrome:

1. Physical Examination : A paediatrician or clinical geneticist will examine the individual for characteristic physical traits and developmental patterns. Aarskog syndrome often presents with specific skeletal, facial, and genital features. Notable facial traits may include wide-set eyes, a short nose with a rounded tip, and a pronounced upper lip.
2. Review of Medical History : The healthcare provider will collect a detailed medical history to identify developmental concerns, learning difficulties, or other related health conditions. A family history is also explored to detect any genetic patterns or similar symptoms in relatives.
3. Genetic Testing : To confirm the diagnosis, molecular genetic testing is usually conducted. This involves analysing the FGD1 gene for mutations using techniques like DNA sequencing. Identifying a mutation in this gene helps to verify the presence of Aarskog syndrome.
4. Chromosomal Evaluation : In certain situations, a chromosomal analysis (karyotyping) may be performed. This test looks at the number and structure of chromosomes, which can help identify abnormalities, particularly those involving the sex chromosomes in males.

In summary, Aarskog syndrome is passed through mutations on the X chromosome, with the likelihood of inheritance and severity depending on whether the mutation comes from the mother, father, or both.