Noonan syndrome

Syndrome description

Noonan syndrome is a dysmorphic syndrome characterized after birth by: a particular aspect of facial features (hypertelorism, a downward eye slant, low-set posteriorly rotated ears), short stature, a webbed neck, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. Sometimes there is an intellectual deficit and a delay in language acquisition.
The final diagnosis of Noonan syndrome is also challenging in postnatal life, and it is based on clinical features due to its genetic heterogenety; several scoring systems have been used.

Prevalence

4 children out of 10.000

Noonan syndrome affects boys and girls equally. This disease is not specific to a particular population or region.

Codification

Orpha: 648
OMIM: 163950 605275 609942 610733 611553 613224 613706 615355 616559 616564 618499 618624 619087
UMLS: C0028326
MeSH: D009634
GARD: 10955
MedDRA: 10029748

A bit of history

The first complete description appears to be that of Weissenberg in 1928.
In 1963, Jacqueline Noonan, cardiopediatrician further delineated the clinical phenotype and documented its association with valvular pulmonic stenosis.

Anomalies detectable by ultrasound

Anomalies: very frequent – 80% or more

1st trimester

Cystic hygroma
Increased nuchal translucency

2nd and 3rd trimester

Thickened nuchal skin fold
Webbed neck
High forehead
Downslanted palpebral fissures
Low-set, posteriorly rotated ears
Hypertelorism
Thickened helices
Excessive amount of amniotic fluid

3D assessment of the fetal face may sometimes show the typical coarse facies described postnatally.

Anomalies: frequent 30 – 80%

1st trimester

Polyhydramnios
Hypertelorism
Abnormality of the eye

2nd and 3rd trimester

Pleural effusion
Ascites
Cryptorchidism
Hypoplasia of nasal bones
Short femur
Hypertrophic cardiomyopathy
Peripheral pulmonary stenosis
Pulmonary valve stenosis
Abnormal ductus venosus doppler (reversed a-wave)

Anomalies : occasional < 30%

1st trimester

Abnormality of the umbilical cord
Abnormal heart morphology
Ventricular septal defect
Atrial septal defect
Increased nuchal translucency (T1)
External ear malformation
Pleural effusion

2nd and 3rd trimester

Hydrops
Aplasia of the semicircular canal
Edema of the dorsum of the hands and feet
Absence of Ductus Venosus
Persistence of the Right Umbilical Vein Hydrothorax
Chylothorax
Atrial septal defect
Ventricular septal defect
Tetralogy of Fallot
Aortic coarctation
Aortic stenosis
Atrioventricular canal

Differential diagnosis

Differential diagnoses include Cardio-Facio-Cutaneous syndrome, Costello syndrome, Neurofibromatosis type 1, Noonan syndrome with multiple lentigines (all RASopathies), Baraitser-Winter, Aarskog and Escobar syndromes.

Expert editor: Emmanuel Spaggiari – Last update: 15 May 2022

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