Noonan Syndrome Workup

Updated: Apr 22, 2022
  • Author: Margaret M McGovern, MD, PhD; Chief Editor: Luis O Rohena, MD, PhD, FAAP, FACMG  more...
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Approach Considerations

All patients with Noonan syndrome should be evaluated to determine which disease manifestations they display. A complete physical and neurologic examination should be performed, and a genetics consultation should be sought. In addition, the following assessments should be made at the time of diagnosis:

  • Cardiac evaluation: Including echocardiographic and electrocardiographic assessment

  • Ophthalmologic and audiologic evaluation

  • Coagulation screen

  • Renal ultrasonographic examination

  • Developmental assessment

Before any patient with Noonan syndrome can undergo a surgical procedure, a full hematologic workup must be performed.


Laboratory Studies

Bleeding diatheses are common among patients with Noonan syndrome. The most frequent abnormality is factor XI deficiency, but various disorders have been reported in patients with Noonan syndrome. A complete blood count (CBC) with platelet count, coagulation profile, and measurement of factor XI level should be obtained at a minimum. Moreover, before any patient with Noonan syndrome can undergo a surgical procedure, a full hematologic workup must be performed.

If full phenotypic expression is not apparent, karyotyping may be necessary. Mutation analysis may confirm the diagnosis of Noonan syndrome, but failure to identify a germline mutation in any of the associated genes does not rule out the disorder; this entity remains a clinical diagnosis.

Many individuals with Noonan syndrome have reduced insulinlike growth factor-1 (IGF-1) and IGF-binding protein 3, but these tests are not diagnostic of the syndrome itself.


Imaging Studies

Appropriate imaging studies in Noonan syndrome include the following:

  • Echocardiography

  • Renal ultrasonography

  • Brain and cervical spine magnetic resonance imaging (MRI): If neurologic symptoms are present

  • Radiography: To examine the chest and back if abnormalities are present [1] and to evaluate the patient for Noonan-like/multiple giant cell lesion syndrome (NS/MGCLS)


Other Tests

Any child suspected of having Noonan syndrome requires a detailed cardiac workup. This includes electrocardiography, echocardiography, and consultation with a pediatric cardiologist.

Assessment of development is necessary to identify any delays and allow for intervention. Full-scale intelligence quotient (IQ) ranges from 48-130, with a mean of 86.1 (approximately one standard deviation [SD] below the general population mean). Approximately 25% of patients with Noonan syndrome have mental retardation. A study by Roelofs et al found that in persons with Noonan syndrome, full-scale and performance IQs saw significant improvement in adult scores compared with childhood values, with performance IQ reaching normal levels. However, verbal IQ did not advance proportionately to performance IQ by adulthood. The investigators suggested that the improvement in performance IQ in individuals with Noonan syndrome points to a developmental delay in executive functioning that is outgrown in adulthood. However, maturation of motor skills was also suggested as a reason for the improvement. The study included 16 patients, whose intelligence was evaluated in childhood and adulthood. [27]

As previously mentioned, the incidence of progressive high-frequency sensorineural hearing loss may be as high as 50%. Thus, audiologic evaluation is indicated.

DNA-based testing of the known causative genes, which can be performed via next-generation sequencing, can be considered for confirmation of diagnosis. [28] Unless a known mutation is present in a family, negative (ie, normal) test findings do not rule out a diagnosis of Noonan syndrome.