FRCA Notes

Noonan Syndrome

This topic almost certainly lies outside the purview of the FRCA exam.

If one were to shoehorn it into being relevant, the appropriate curriculum item is: 'recalls/explains the implications of paediatric... syndromes'.

Resources

  • Noonan syndrome causes a classic trifecta of congenital cardiac defects, skeletal/growth abnormalities and characteristic facial abnormalities
  • It resembles Turner syndrome (XO) but with a normal karyotype
  • Incidence 1 in 1,000 - 2,500 without gender preponderance
  • Mutations to the RAS-MAPK signalling pathway cause Noonan syndrome (i.e. it is a RASopathy)
  • Autosomal dominant with variable expression and penetrance, however many cases arise due to de novo mutations

  • PTPN11 gene mutation (50%)
    • Causes the SHP-2 protein to be continuously active instead of switching on/off in response to other proteins
    • Leads to aberrant activation and up-regulation of RAS signalling
    • This disrupts cellular growth and division, resulting in abnormal features of Noonan syndrome

Diagnosis

  • Primarily clinical based on characteristic appearance and clinical features
  • Sometimes confused with King-Denborough syndrome
  • Confirmation via molecular testing


Characteristic appearance/airway changes
Macrocephaly
Hypertelorism
Down-slanting palpebral fissures
High-arched eyebrows
Epicanthic folds
Depressed nasal root with wide nasal base
Full upper lip
Dental malocclusion (50-67%)
High-arched palate (55-100%)
Micrognathia (33-43%)
Broad/webbed neck (pterygium colli)
Occasionally associated with multiple giant cell neoplasms of the jaw

Cardiovascular

  • Pulmonary valve stenosis (50-60%)
  • Hypertrophic cardiomyopathy (20%)
  • ASD (8%)
  • VSD (5%)
  • PDA (3%)

  • 50% have abnormal ECG, especially in those with hypertrophic cardiomyopathy, characterised by:
    • LAD
    • Abnormal R/S ratio over the left precordial leads
    • Abnormal Q-wave

Neurological

  • Psychomotor deficit
  • Cognitive deficits (25%)
  • Ocular abnormalities
  • Hydrocephalus
  • Arnold-Chiari I
  • Atlanto-axial dislocation

Genitourinary

  • Cryptorchidism
  • Infertility (males)
  • Delayed menarche
  • Other renal abnormalities

Gastrointestinal

  • Feeding difficulties
  • GORD
  • Splenomegaly

Haematological

Abnormal bleeding due to variable abnormalities in up to 75%
Partial factor XI deficiency (commonest; 25%)
Prolonged PT
Prolonged APTT
Abnormal platelet count
Prolonged bleeding time
Low factor XII activity
Low factor VIII activity
von Willebrand disease
Factor IX deficiency (rare)
Factor II deficiency (rare)
  • Significant surgical bleeding has been reported even in patients with normal clotting assays and platelet counts

  • Occasionally associated with:
    • Malignancy, particularly leukaemia
    • Transient myeloproliferative disorder of infancy

Other features

  • Growth delay of post-natal onset
  • Mild/moderate, proportionate short stature (50%)
  • Pectus carinatum or excavatum
  • Spina bifida and other vertebral or rib anomalies
  • Cubitus valgus
  • Hyperkeratosis or eczema

Perioperative management of the patient with Noonan Syndrome


  • Common surgeries include:
    • Cardiac surgery to correct defects
    • Surgical correction of cryptorchidism in males
    • Ocular surgery
    • Oral surgery inc. adenoidectomy
    • Correction of pterygium colli

History and examination

  • Standard paediatric history
  • Cardiac and haematological abnormalities and management thereof
  • Cardiorespiratory function
  • Robust airway assessment

Investigations

  • Bloods
    • FBC
    • Coagulation studies including PT, APTT, platelet count, factor XI levels and bleeding time
    • May need further specific testing depending on exact clotting/bleeding dyscrasia
    • Group and cross match ± preparation of other specific transfusion products based on individual needs e.g. FFP

  • Consider respiratory investigations if significant chest wall deformities; CXR, ABG and lung function tests

  • Cardiovascular investigations: ECG, TTE

Planning and optimisation

  • Close liaison with Haematology regarding nature, and optimal management, of haematological issues in the perioperative period
  • Liaison with Paediatric and Surgical teams
  • Not suitable for day-case surgery; plan for overnight stay ± HDU/PICU care depending on nature of surgery
  • Airway planning

Monitoring and access

  • AAGBI
  • Patients with pulmonary stenosis may require arterial line ± CVC depending on the nature of surgery

Induction technique

  • Anticipate difficult airway in children due to presence of multiple facial aberrations, although adults may have more normal airway anatomy
  • Induction techniques which maintain spontaneous ventilation may therefore be preferable given the inability to perform awake intubation in paediatric patients
  • May need to modify induction technique according to nature and degree of cardiac anomalies

  • General goals are:
    1. Minimise sympathetic activation
    2. Avoid direct or reflex increases in cardiac contractility or HR
    3. Avoid hypovolaemia (IV fluid) or significant hypervolaemia (furosemide, amiloride)
    4. Avoid significant reductions in LV afterload

Regional anaesthesia

  • Skeletal defects (kyphoscoliosis and lumbar lordosis) may complicate regional anaesthetic techniques
  • Neuraxial techniques may be contraindicated by cardiac features
  • Use of regional anaesthesia is documented

Care bundle

  • Consider endocarditis prophylaxis in patients deemed at risk
  • Maintain euthermia
  • Not associated with thromboembolism so VTE prophylaxis as for other paediatric patients

Obstetrics

  • At risk of haemodynamic instability due to interplay of:
    • Sympathetic stimulation from labour pain
    • Episodic, prolonged Valsalva manoeuvre
    • Increased blood volume during uterine contractions/placental auto-transfusion
    • Reduced blood volume due to bleeding
    • Co-existing cardiovascular disease

  • Complex airway management owing to:
    • Pre-existing airway difficulties
    • Added risks associated with the obstetric population
    • Potential difficulties in administering neuraxial anaesthetic techniques

  • Close monitoring for 24hrs with regards to cardiorespiratory parameters
  • Avoid factors which may cause cardiorespiratory strain such as:
    • Uncontrolled pain
    • Hypovolaemia ± hypotension
    • Hypothermia
    • Other sympathetic stimulation

  • RV failure due to increased PVR or excessive IV fluid administration
  • Only weak evidence to suggest any association with malignant hyperpyrexia
  • Large volume, unexpected intra-operative blood loss