Aarskog-Scott Syndrome

Aarskog-Scott syndrome (faciogenital dysplasia) is an X-linked disorder caused by pathogenic variants in FGD1, with short stature, hypertelorism, a shawl scrotum, brachydactyly and joint laxity.

Male patients are affected, and carrier females have mild features.

Pathophysiology

FGD1 encodes a guanine nucleotide exchange factor for the small GTPase CDC42, which controls the actin cytoskeleton during bone and tissue growth.

Loss of function disrupts skeletal and genital development.

About 30% of cases are de novo, and the rest are inherited from carrier mothers.

Intelligence is normal or mildly reduced, with ADHD and learning problems common.

• Short stature with delayed pubertal growth spurt
• Hypertelorism, ptosis, broad nasal bridge, anteverted nares and long philtrum
• Widow's peak and a round face
• Shawl scrotum (scrotal fold surrounding the penis base), cryptorchidism and inguinal hernia
• Brachydactyly, clinodactyly, interdigital webbing and broad feet
• Joint laxity with genu recurvatum, and pectus excavatum
• Cervical spine anomalies (odontoid hypoplasia, instability)
• ADHD, learning difficulty, mild intellectual disability
• Dental anomalies and delayed eruption

• FGD1 sequencing with deletion and duplication analysis.
• Clinical assessment: facial features, genitalia, hands and growth.
• Cervical spine imaging (lateral flexion and extension views or MRI) before anaesthesia or sport.
• Bone age and growth evaluation.
• Developmental and behavioural assessment.
• Carrier testing of female relatives.

• Short stature: monitor height. Growth hormone 0.033 mg/kg subcutaneously daily has been used with variable response, and is a specialist decision.

• Genital and urological care: orchidopexy for cryptorchidism, and hernia repair.

• Cervical spine: if instability, avoid contact sports, inform the anaesthetist, and consider fusion for symptomatic instability or cord compression.

• ADHD: methylphenidate 5 mg orally once or twice daily increasing weekly by 5 to 10 mg to a usual maximum of 60 mg daily, with growth and blood pressure monitoring. Behavioural support alongside.

• Education and development: assessment for learning difficulties, and an individual education plan.

• Dental care: orthodontic review and regular dental treatment.

• Orthopaedic care: physiotherapy for joint laxity, and treatment of pectus if symptomatic.

• Genetic counselling: a carrier mother has a 50% chance of passing the variant to each child; sons are affected and daughters are carriers.

Special groups

• Carrier females: examine for mild features such as short stature and hypertelorism.

Monitoring. Growth, development and behaviour every 6 to 12 months. Cervical spine review before major procedures, and dental review every 6 months.

Referral and escalation. Refer to clinical genetics, paediatric endocrinology and urology. Urgent for neck pain, limb weakness or other signs of cord compression.