Noonan syndrome
Updates to Article Attributes
Noonan syndrome (NS) is a genetically and phenotypically heterogeneous non aneuploidic-aneuploidic congenital RASopathy. Affected individuals can bear some clinical features similar to that of Turner syndrome.
Epidemiology
The estimated incidence is at ~1 in 1000-2500 10. As individuals have normal number of chromosomes, both males and females can be affected.
Clinical presentation
An immense number of clinical features have been described which can be present at varying degrees. These include:
- craniofacial
- telecanthus, hypertelorism
- low-set ears, rotated ears +/- thickened helix
- epicanthus
- facial asymmetry
- intellectual disability
- microgenia
- low neck hairline
- cervicothoracic
- pterigium colli: webbed neck
- winged scapulae
- pectus excavatum
- pectus carinatum
-
- pulmonary stenosis (with dysplastic pulmonary valve): most common cardiac anomaly 3
- hypertrophic cardiomyopathy 3,4: thought to affect ~20% of individuals 3
- patent ductus arteriosus (PDA)
-
generalised musculoskeletal
- renal anomalies
- dilated renal pelvices 6,9
Pathology
Genetics
The inheritance is autosomal dominant although a significant proportion of cases are sporadic 8. Many genes have been implicated, the most common being the PTPN11 gene which encodes for SHP2, which results in an inability to inactivate SHP2 causing increased signalling of the Ras/MAPK pathway. However. other genes that may be less commonly implicated including SOS1, KRAS, RAF1, NRAS, and SHOC2 10. Because of its effect in amplifying the Ras/MAPK pathway, it is considered to be a RASopathy 10.
Radiographic features
Antenatal ultrasound
Early 1st trimester ultrasound may show nuchal oedema or a cystic hygroma similar to that of Turner syndrome. With subsequent scanning, some of the above individual clinical features may be present sonographically.
History and etymology
It is named after Jacqueline A Noonan (1928-fl 2019), an American paediatric cardiologist 11.
-<p><strong>Noonan syndrome (NS)</strong> is a genetically and phenotypically heterogeneous non aneuploidic congenital <a href="/articles/rasopathy-1">RASopathy</a>. Affected individuals can bear some clinical features similar to that of <a href="/articles/turner-syndrome">Turner syndrome</a>. </p><h4>Epidemiology</h4><p>The estimated incidence is at ~1 in 1000-2500 <sup>10</sup>. As individuals have normal number of chromosomes, both males and females can be affected. </p><h4>Clinical presentation</h4><p>An immense number of clinical features have been described which can be present at varying degrees. These include:</p><ul>- +<p><strong>Noonan syndrome (NS)</strong> is a genetically and phenotypically heterogeneous non-aneuploidic congenital <a href="/articles/rasopathy-1">RASopathy</a>. Affected individuals can bear some clinical features similar to that of <a href="/articles/turner-syndrome">Turner syndrome</a>. </p><h4>Epidemiology</h4><p>The estimated incidence is at ~1 in 1000-2500 <sup>10</sup>. As individuals have normal number of chromosomes, both males and females can be affected. </p><h4>Clinical presentation</h4><p>An immense number of clinical features have been described which can be present at varying degrees. These include:</p><ul>
-<p>cardiopulmonary</p>-<ul>- +<a href="/articles/pectus-carinatum">cardiopulmonary</a><ul>
-<p>vascular</p>-<ul><li>- +<a href="/articles/patent-ductus-arteriosus">vascular</a><ul><li>
- +<li>generalised musculoskeletal<ul>
- +<li><a href="/articles/short-stature">short stature</a></li>
- +<li><a href="/articles/short-stature">hypotonia</a></li>
-<p>generalised musculoskeletal</p>-<ul>-<li><p><a href="/articles/short-stature">short stature</a></p></li>-<li><p><a href="/articles/short-stature">hypotonia</a></p></li>-<li><p><a href="/articles/delayed-sternal-ossification">delayed sternal ossification</a> <sup>7</sup></p></li>- +<a href="/articles/delayed-sternal-ossification">delayed sternal ossification</a> <sup>7</sup>
- +</li>