Makindo Medical Notes

Related Subjects: |Autosomal Dominant |Autosomal Recessive |X Linked Recessive

Named after an American pediatric cardiologist, Jacqueline Noonan, Noonan syndrome is a genetic disorder that affects both males and females. Almost all children with Noonan syndrome reach adulthood and are able to lead normal, independent lives, although heart defects and other complications can occasionally be severe and life-threatening.

About

• Noonan syndrome is a genetic disorder characterized by distinctive facial features, heart defects, and other developmental issues.
• It is sometimes referred to as "Male Turner syndrome" due to similarities in some features, though it affects both sexes.
• It affects 1 in 2,500 live births, regardless of sex or ethnicity.

Aetiology

• Noonan syndrome is inherited in an Autosomal Dominant pattern, meaning only one copy of the mutated gene is necessary for the condition to occur.
• It is often associated with mutations in genes related to the RAS/MAPK pathway, particularly PTPN11 on chromosome 12, which plays a role in cell growth and development.
• At least eight specific genetic mutations have been identified, including SOS1, RAF1, and KRAS.

Clinical Features

• Growth: Short stature often becomes apparent around age two, with growth delays persisting through childhood.
• Facial Features: Characteristic dysmorphic facial features, such as a triangular face, widely spaced eyes, low-set ears, and ptosis (drooping eyelids).
• Cardiovascular:
  • Pulmonary Stenosis: The most common heart defect in Noonan syndrome.
  • Hypertrophic Cardiomyopathy: Seen in 20-30% of patients and may lead to complications over time.
  • Septal Defects: Atrial and ventricular septal defects can occur, contributing to congenital heart disease.
• Developmental: Mild intellectual disability or learning difficulties, delayed motor milestones, and hypotonia (reduced muscle tone).
• Hematological: Increased risk of bleeding due to conditions like factor XI deficiency.
• Other Features: Delayed puberty in males, cryptorchidism (undescended testes), and a tendency toward low muscle tone.

Differential Diagnosis

• Turner Syndrome: Noonan syndrome shares several physical characteristics with Turner syndrome, such as short stature and certain facial features, but Turner syndrome occurs in females with a missing X chromosome (45,X).
• Cardio-facio-cutaneous (CFC) Syndrome: Similar genetic pathways are involved, with overlapping features like heart defects and developmental delays.
• Costello Syndrome: Another RASopathy with overlapping characteristics, including similar facial features and developmental delays.

Management

• Cardiac Care: Regular monitoring and treatment of heart defects, including surgical intervention for significant pulmonary stenosis or cardiomyopathy as needed.
• Growth Hormone Therapy: May be considered for treating short stature, especially if growth is significantly delayed.
• Developmental Support: Early intervention with speech therapy, physical therapy, and special education can improve outcomes for developmental delays.
• Hematologic Monitoring: Regular monitoring and management of bleeding disorders, such as factor XI deficiency, to prevent complications during surgery or injury.
• Multidisciplinary Approach: A team including cardiologists, endocrinologists, geneticists, and developmental specialists is often required for comprehensive care.