Investigations
1st investigations to order
ECG
Test
Congenital heart defects are present in up to 75% of cases; so, if NS is suspected, a cardiovascular examination with ECG should be performed.[1]
The most common cardiac anomalies include dysplastic and/or stenotic pulmonary valve, hypertrophic cardiomyopathy, septal defects, and tetralogy of Fallot.[30][55][56][57]
Result
wide QRS complexes, with a predominantly negative pattern in the left precordial leads (62%); left axis deviation, and giant Q waves
echocardiogram
Test
Congenital heart defects are present in up to 75% of cases; so, if NS is suspected, a cardiovascular examination with echocardiogram should be performed.[1]
The most common cardiac anomalies include dysplastic and/or stenotic pulmonary valve, hypertrophic cardiomyopathy, septal defects, and tetralogy of Fallot.[30][55][56][57]
Result
may show congenital heart defects
Investigations to consider
FBC
Test
Bleeding diatheses are not uncommon, and if NS is suspected, screening for coagulation abnormalities should be considered, particularly if there is easy bleeding or bruising, or surgery is planned.[53]
A mild-to-moderate bleeding tendency is not uncommon, although prevalence in the literature varies dramatically, and multiple types of coagulation defects and bleeding diatheses have been documented.[42][53][52] Severe haemorrhage has been reported to occur in 3% of cases.
Platelet depletion may be secondary to ineffective production, with reduced or absent megakaryocytes in the bone marrow, or may occur because of sequestration in an enlarged and/or myelodysplastic spleen.[40]
Result
anaemia, thrombocytopenia
coagulation profile
Test
Bleeding diatheses are not uncommon, and if NS is suspected, screening for coagulation abnormalities should be considered, particularly if there is easy bleeding or bruising, or surgery is planned.[53]
A mild-to-moderate bleeding tendency is not uncommon, although prevalence in the literature varies dramatically, and multiple types of coagulation defects and bleeding diatheses have been documented.[42][53][52] Severe haemorrhage has been reported to occur in 3% of cases.
If coagulation abnormalities are present, the patient should be referred to a haematologist for further assessments.[60]
Result
prothrombin time, activated partial thromboplastin time, bleeding time may be prolonged
molecular genetic testing
Test
May be necessary when the diagnosis is equivocal, or for family reasons (e.g., parental diagnosis, determination of the risk for recurrence, or reproductive planning).
Clinical diagnostic testing for all genes in the Ras/MAPK pathway known to cause Noonan syndrome is available. However, a proportion of people with NS will not have a mutation in any of these genes.
Some laboratories suggest testing in a tiered manner, beginning with the PTPN11 hotspots (serial single gene testing). Other laboratories use a multigene panel that simultaneously tests for all genes known to cause Noonan syndrome.
Result
characteristic mutations of associated genes (e.g., PTPN11, SOS1, RAF1, RIT1, RASA2, LZTR1, SHOC2, KRAS, NRAS, BRAF, and MAP2K1)
abdominal ultrasound
Test
Should be performed if enlargement of the spleen is suspected.
Splenomegaly may be a feature of myelodysplasia.[40]
Result
may show splenomegaly
renal ultrasound
Test
Should be performed if renal malformation is suspected (e.g., malformations such as duplex collecting system, distal ureteric stenosis, renal hypoplasia, unilateral renal agenesis, or unilateral renal ectopia); this may be present in up to 10% of cases.[50]
Result
may show malformations
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