Noonan, syndrome
|
[MIM 163 950, 605 275, 609 942, 611 553, 613 224, 613 563, 613 706]
Prevalence: 1/1,000 to 1/2500. Autosomal dominant transmission with variable penetrance of a mutation in the chain of RAS-MAPK reactions, an important route of transmission of extracellular signals (hormonal etc) to the nucleus influencing cell proliferation and differentiation as well as metabolism. It is a multisystemic disease. A mutation in one of 8 genes located on 12q24.1 and coding for proteins of the RAS-MAPK pathway can cause Noonan or similar (LEOPARD, Costello and cardio-facio-cutaneous) syndrome, grouped under the name of RASopathies (see this term).
Association of:
- low implanted and posteriorly rotated ears, with a thick helix
- epicanthus and blue-gray or blue-green colored iris with arched eyebrows, palpebral ptosis
- micrognathia (50 %)
- evolution of the facial dysmorphism according to age:
age |
front/side |
eyes |
nose |
mouth |
neck |
newborn |
high forehead |
hypertelorism epicanthus downslanting
|
short and thick, upturned tip, wide base |
very marked philtrum, micrognathia |
excess nuchal skin |
infant |
large head, high and prominent forehead |
hypertelorism, ptosis |
short and wide, depressed base |
same |
same |
child |
elongated
|
same |
high and fine
|
same |
same |
teenager |
myopathic facies. |
same |
important nasolabial folds |
same |
pterygium coli (webbing) |
adult |
less typical features, looking thin-looking and transparent skin |
same |
same |
same |
same |
At birth: hypotonia, severe feeding difficulties.
Genotype/phenotype correlation
Gene |
heart |
size |
development |
skin/hair |
other |
PTPN11
|
mainly pulmonary stenosis, less often ASD and cardiomyopathy |
short stature |
some mutations lead to little or no cognitive impairment |
|
problems of hemostasis and leukemia |
SOS1
|
decreased risk of ASD |
less risk of short stature |
decreased risk of mental retardation |
more nevi, lentigines and
|
rhythm
|
RAFT1
|
mainly hypertrophic cardiomyopathy |
same |
same |
more nevi, lentigines and
|
|
KRAS
|
same |
same |
severe cognitive deficit |
|
|
NRAS
|
same |
same |
same |
|
|
BRAF |
|
short stature |
|
more nevi, lentigines and
|
dolichocephaly |
Anesthetic implications:
recent cardiac check-up and management according to the cardiac problem; check (including platelets count and function) hemostasis and blood count. Possible difficult intubation. Difficult venous access. One case of narrow lumbar canal has been reported. Avoid low blood pressure and ensure normoventilation given the possible cerebrovascular abnormalities. In teenagers, verify the absence of an Arnold-Chiari syndrome (see this term)
References :
Updated: August 2022