Question

Disease paper on Noonan Syndrome

Answer 1

The functions of SHP2  is expressed throughout the body and is an important player in cellular responses to growth factors, hormones, cytokines, and cell adhesion molecules

*Noonan syndrome is a genetic disorder that prevents normal development in various parts of the body.

*Noonan syndrome is caused by the mutation in the PTPN11 gene, mapped to chromosome 12q24.1, which encodes the non-receptor protein tyrosine phosphatase SHP2.

* Mutation in PTPN II gene is common inNoonann patients with

*Mutation result in the gain of function for SHP2
- SHP2 is essential in several intracellular signal transduction pathways and controls a number of developmental processes including semi-lunar valve development

*Noonan syndrome affects individuals :

1. unusual facial characteristics

2. short stature

3. heart defects

4. other physical problems and possible developmental delays

*Common characteristics:

1. cardiac disease

2. short stature

3. facial anomalies

4. chest deformities

5. increased bleeding or bruising

6. cognitive disabilities

*Characteristic facies (hypertelorism, downward eye slant, and low-set ears)**
*Short Stature
*Chest deformity (pectus excavatum)
*Pulmonary stenosis

Other findings
- undescended testes
- learning difficulties
- Scoliosis, kyphosis
- thrombocytopenia
- muscular hypotonia
- hepatosplenomegaly
- kidney abnormality
- webbing of the neck
- unusual EKG

*Effects of Noonan syndrome on speech and/or language:

1. feeding and nutrition problems

2. mild hearing loss

3. motor dexterity difficulties

4. speech and/or language delay

-Many Noonan syndrome individuals have high arched palate which influences articulation

-Many NS children have teeth that are wrongly positioned which influences articulation

*The types of inheritance in Noonan syndrome:

Autosomal dominant inheritance
- no preferential sex affected

*The clinical presentation of a newborn with Noonan syndrome:

- excess nuchal skin
- Edema
- Forehead sloping and broad
- Posteriorly rotated thick ears
- May have down-slanting eyes
- Hypertelorism (abnormal distance between the eyes)

*The individuals with Noonan syndrome bruise easily due to factor XI deficiency

* The most common cardiovascular finding in Noonan syndrome is:

Valvular Pulmonary stenosis - often dysplastic associated ASD and pulmonary artery branch stenosis

*It .can be diagnosed by a pediatrician by genetic testing and physical characteristics of individuals.

*Unusual EKG findings are seen in Noonan syndrome.

*Management:

• Manage the pulmonary symptoms of Noonan

- valvectomy often required
- resection anomalous muscle bundles
- outflow patch may be needed

• The management for Hypertrophic cardiomyopathy seen in Noonan's:

- Beta-blockers in infancy effective
- Calcium channel blockers effective
- Surgery in symptomatic obstructed HCM
- Cardiac transplant may be needed