Rasopathy

Gene: SOS2

Green List (high evidence)

Over 20 affected individuals reported. The overall phenotype fits well into the spectrum of Noonan syndrome and is most similar to the phenotype observed in patients with SOS1-related Noonan syndrome, with ectodermal anomalies as common features and short stature and learning disabilities as relatively infrequent findings compared to the average Noonan syndrome phenotype. The spectrum of heart defects in SOS2-related Noonan syndrome is consistent with the known spectrum of cardiac anomalies in RASopathies, but no specific heart defect was particularly predominating. Notably, lymphatic anomalies were extraordinarily frequent, affecting more than half of the patients, manifesting as increased NT and hydrops antenatally, and congenital chylothorax in the newborn period. Notably, lymphedema occurring after newborn period, such as lymphedema of lower limbs and genitalia, was found in almost half of the reported individuals.

The missense changes c.791C>A p.(Thr264Lys), c.800T>G p.(Met267Arg), c.800T>A p.(Met267Lys), and c.1127C>G p.(Thr376Ser) are recurrent.

Created: 11 Sep 2020, 9:55 p.m. | Last Modified: 11 Sep 2020, 9:55 p.m.

Panel Version: 0.78

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Noonan syndrome 9, MIM# 616559

Publications

• 26173643
• 25795793
• 32788663

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments