Paula and Bobby
Parents of Lillie
What is Noonan syndrome?
A genetic disorder that presents with unusual facial characteristics and short stature. Health conditions associated with this disorder include eczema, developmental delay, short stature, webbed neck, pulmonic stenosis, and unique facial features. It is an inherited genetic condition, and just one copy of the mutated gene in each cell is enough to cause the disorder.
Female Pseudo-turner Syndrome, Male Turner Syndrome, Noonan syndrome, Turner Phenotype With Normal Karyotype
What gene changes cause Noonan syndrome?
Noonan syndrome is part of a group of related conditions known as RASopathies. Changes in one of several autosomal-dominant genes cause the syndrome. Around half of all cases are caused by mutations in the PTPN11 gene, with a further 10-15% of cases caused by SOS1 gene mutations. Mutations in the RAF1 and RIT1 genes are accounting for around 5% of cases. And a further 15-20% of cases present with cause unknown. The PTPN11, SOS1, RAF1, and RIT1 genes are responsible for providing the instructions for making proteins needed for cell division and growth. Mutations in the genes associated with Noonan syndrome cause this protein to be active longer than normal rather than switching on and off in response to cell signals. This then disrupts cell growth regulation and leads to characteristic clinical features of Noonan syndrome.
In the case of autosomal dominant inheritance just one parent is the carrier of the gene mutation, and they have a 50% chance of passing it onto each of their children. Syndromes inherited in an autosomal dominant inheritance are caused by just one copy of the gene mutation.
Genes, locations, and inheritance modes
RRAS, 19q13.33 - Autosomal Dominant
OMIM Number - 163950 (please check the OMIM page for updated information)
What are the main symptoms of Noonan syndrome?
The main symptoms of Noonan syndrome include characteristic facial features such as a deep groove between the nose and mouth, widely spaced eyes that are often pale blue or blue-green, and low-set ears rotated backward. A high arch in the roof of the mouth, a small lower jaw, and excess neck skin or webbing are also all characteristic of the syndrome. Children with Noonan syndrome are often both a normal length and weight at birth, but their growth slows over time. Individuals with the syndrome may also have a sunken or protruding chest.
Congenital heart disease can also be a symptom of Noonan syndrome, specifically a narrowing of the valve that controls blood flow from the heart to the lungs. Individuals may also present twitch hypertrophic cardiomyopathy, which enlarges and weakens the heart muscle.
Eczema and bleeding disorders are also a dominant symptom of Noonan syndrome leading to excessive bruising and nosebleeds.
Noonan syndrome leads to delayed puberty in male adolescents and possible infertility related to undescended testes.
Most individuals with Noonan syndrome are of normal intelligence, but a developmental delay is a common symptom. Vision and hearing problems are also potential symptoms.
How does someone get tested for Noonan syndrome?
The initial testing for Noonan syndrome can begin with facial analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the need for further testing. A consultation with a genetic counselor and then a geneticist will follow.
Based on this clinical consultation with a geneticist, the different options for genetic testing will be shared and consent will be sought for further testing.
Medical information on Noonan syndrome
Hoban et al., (2012) reported an infant with features of Noonan syndrome, but with a severe hypertrophic cardiomyopathy and a SHOC2 mutation. Cordeddu et al., (2009) had previously reported the same, but with in addition the loose anagen hair syndrome.
Note that some patients with SHOC2 and PTPN11 mutations (Ekvall et al., 2011) can have a severe phenotype, but without a lethal cardiomyopathy.
Gripp et al., (2013) reported a new patient and review the condition. Their patient also had loose anagen hair syndrome and myelofibrosis. Four out of 4 have had to date a structural cardiac anomaly and 80% have had hypotonia and macrocephaly. Skin hyperpigmentation, sparse lightly coloured hair and increased fine skin wrinkles are common. There is also relative megalencephaly and a benign external hydrocephalus. Severe craniosynostosis was documented in the case reported by Takenouchi et al., (2014). Two further patients were reported by Baldassarre et al., (2014). There was extremely different phenotypic expression in the severity of the cardiac lesion and the intellectual disability."
* This information is courtesy of the L M D.
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