Endocrine Abstracts

Introduction: Noonan syndrome (NS) is an autosomal dominant genetic disorder characterized by the combination of facial dysmorphia, short stature and congenital heart disease. The mutation of the PTPN11 gene is present in 50% of cases, recently the mutation of other genes was found, notably KRAS and SOS1. We report the case of a patient followed in our department for NS with a SOS1 gene mutation.

Case report: A 4 years old male patient, referred to our department for failure to thrive (FTT). The diagnosis of NS was made in view of a typical facial dysmorphia, a congenital cardiac disorder with a moderately tight pulmonary valve stenosis, a bicuspid aortic valve and a non-stenosing sub-aortic septal hypertrophy for which the patient was operated, as well as a FTT with a weight and a height between - 2 and - 3 standard deviation (SD). A left cryptorchidism was also found on clinical examination. The genetic study found a pathogenic variant of the SOS1 gene with autosomal dominant RASopathy. For his FTT, the first line workup was normal. IgF1 was normal for the age of the patient. The glucagon test wasn’t in favor of growth hormone (GH) insufficiency.

Discussion and conclusion: At present, seven genes have been shown to be associated with NS: PTPN11, SOS1, RAF1, KRAS, NRAS, SHOC2, and CBL. The most common gene associated with NS is PTPN11, which accounts for approximately 50% of all cases. SOS1 missense mutations are the second-most-common cause of NS, accounting for approximately 15% of cases. NS is one of a group of genetic diseases called RASopathies. They are clinically defined as a group of medical genetic syndromes caused by germline mutations in genes that encode components or regulators of the Ras-mitogen-activated protein kinase (MAPK) pathway. These disorders include neurofibromatosis type 1, Noonan syndrome, Noonan syndrome with multiple lentigines, capillary malformation–arteriovenous malformation syndrome, Costello syndrome, cardiofaciocutaneous syndrome, and Legius syndrome. They have in common many symptoms. In our patient, Costello syndrome was also discussed as a diagnosis, but we did not find an abnormality of the HRAS gene.