Discussion
To date, only few studies regarding the perinatal findings in Noonan
syndrome have been described in medical literature. In the prenatal
period, the most common clinical characteristics that have been reported
are lymphatic anomalies, such as increased nuchal translucency, pleural
effusions, cystic hygroma, hydrops fetalis. Long bones <5°
centile have been described in almost half of cases. Other common
prenatal findings in NS are: polyhydramnios, macrosomia (defined as
abdominal circumference >90th centile), occipital-frontal
circumference >90th centile, congenital heart defects.
Arrhythmias have been reported only once in medical literature.
Regarding neonatal findings, cardiovascular anomalies, such as
structural heart defects, valvular dysplasia, hypertrophic
cardiomyopathy are the most common features. Lymphatic dysplasia, birth
weight and occipital-frontal circumference >90th centile,
renal defects and hypotonia are anomalies frequently described in
infants affected by NS. 10
During the prenatal period our patient showed specific findings of NS:
increased nuchal translucency, right caliectasis, polyhydramnios,
abdominal circumference and occipital-frontal circumference
> 90th centile, hydrops fetalis.
At birth other anomalies became evident, such as length
>97th centile, long fingers and toes, megalencephaly, and
Wolff-Parkinson-White syndrome (WPW). Those characteristics are not
typical of Noonan syndrome. Wolff-Parkinson-White syndrome has never
been associated with Noonan syndrome.
WPW syndrome is characterized by the presence of an accessory
atrioventricular pathway, which bypasses the normal atrioventricular
conduction. This pathway leads to a ventricular pre-excitation, causing
palpitations, syncope, ventricular fibrillation and even sudden cardiac
death. 11, 12
Recently, variants in the PI3K-AKT pathway have been described to
be associated with overgrowth syndromes (PIK3CA-Related Overgrowth
Spectrum, PROS), such as Megalencephaly-capillary
malformation-polymicrogyria syndrome (MCAP, MIM # 602501) and
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome-1
(MPPH, # MIM 603387), but also Congenital lipomatous asymmetric
overgrowth, epidermal naevi, skeletal and spinal anomalies syndrome
(CLOVES, # MIM 612918), as well as hemimegalencephaly and isolated
macrodactyly. 13 For this reason, the analysis of a
panel of genes involved in the PI3K/AKT/mTOR pathway was
performed from a saliva sample of our patient and the gene panel testing
came back negative. Since PROS shows phenotypic variability and it is
mostly caused by somatic PI3KCA mutations, it could be important
to follow the child over time, in order to monitor the onset of other
signs related to PROS. It could be interesting to perform the analysis
of a panel of genes involved in the PI3K-AKT pathway in other tissues as
well. Indeed, it cannot be excluded that PIK3CA mutant cells
might exert growth-promoting effects on adjacent or distant cells by
signal propagation of secreted biomolecules or exosomes.