Eye anomalies

95%

—

Short stature

50%-70%

For age, sex, family background

Hypotonia

Majority

Can contribute to feeding problems, speech articulation issues, delayed attainment of gross motor milestones

Joint hyperextensibility

Majority

—

Pectus anomaly

Majority

Characteristic pectus deformity of the chest: pectus carinatum superiorly pectus excavatum inferiorly

Cryptorchidism in males

60%-80%

—

Congenital heart disease

50%-80%

25%-71% of affected persons have pulmonary valve stenosis, often w/pulmonary valve dysplasia.

Hearing loss

40%

May be sensorineural, conductive, or mixed

Hypertrophic cardiomyopathy

10%-29%

Half of those w/hypertrophic cardiomyopathy are diagnosed by age 6 mos.

Learning disability

25%

~10%-15% of those w/NS require special education.

Intellectual disability1

6%-23% Renal anomalies

11%

Abnormal bleeding or bruising

Bleeding: 6%-10%; bruising: majority

1. Defined as IQ 70 Prenatal features. Advanced paternal age has been observed in cohorts with simplex NS.

Constitutional

Measurements of growth parameters

On NS-specific growth charts; To identify those w/failure to thrive /or short stature

Endocrine

Bone age, growth hormone thyroid function studies1

In children w/short stature (height 2 SD below standard growth curve or crossing 2 major height %iles) Gastrointestinal/

Feeding

Gastroenterology / nutrition / feeding team eval

In infants w/poor weight gain, dysphagia; Eval for malrotation if persistent unexplained vomiting

Development

Developmental assessment

To incl:; Motor, adaptive, cognitive, speech-language eval; Eval for early intervention/ special education Psychiatric/

Behavioral

Neuropsychiatric eval may be considered.

For those age 12 mos: screen for behavior concerns, autism, depression, ADHD, anxiety (some symptoms may not be present until adulthood).

Cardiovascular

Echocardiogram EKG

To identify congenital heart defects, cardiomyopathy, /or cardiac conduction abnormalities

Genitourinary

Kidney ultrasound

To assess for renal anomalies; if present, referral to urologist Assessment for cryptorchidism in males

Musculoskeletal

PT/OT eval

To incl:; Assessment of gross motor fine motor skills Consider radiographs of the spine if asymmetry or scoliosis is present on physical exam.

Lymphatic

In consultation w/hematologist: bleeding history, CBC w/differential, PT/aPTT, factor XI, XII, IX, VIII, vWf, platelet aggregation testing

If initial screening was performed before age 12 mos, repeat after age 12 mos.2

Eyes

Ophthalmologic eval

To assess for amblyopia, refractive error, nystagmus, strabismus, clinically significant ptosis

Hearing

Audiologic eval

Assess for hearing loss middle ear effusion.

Integument

Full skin exam

Consider referral to dermatologist in those w/multiple lentigines requiring monitoring or significant xeroderma.3

Neurologic

Neurologic eval

To incl brain spine MRI if signs or symptoms consistent w/possible Chiari malformation Genetic

counseling

By genetics professionals4

To obtain a pedigree inform affected persons their families re nature, MOI, implications of NS to facilitate medical personal decision making Family support resources

Noonan Syndrome: Treatment of Manifestations Manifestation/Concern

Treatment

Considerations/Other

Short stature

GH therapy may be considered.

No standard dose has been established.; No apparent correlation between dosage used final height, though earlier age at initiation of GH therapy is assoc w/ final adult height.; Short stature due to NS is an FDA-approved indication for GH treatment.

difficulties

Consideration of nasogastric tube feedings in infants w/poor growth, esp if they have a congenital heart defect or cardiomyopathy

Invasive intervention (i.e., placement of gastrostomy tube) may be needed, though feeding issues are often self-limited. DD/ID