ESPE Abstracts

Introduction: Noonan syndrome (NS) is an autosomal dominant disorder that involving multiple organ systems, with an incidence of 1:1,000 to 1:2,500.The clinical features as short stature, dysmorphic facial features, congenital heart defects most commonly pulmonary valve stenosis, typical chest, cryptorchidism. The PTPN11 gene is located on the long arm of chromosome 12q24.1 and encodes for the non-receptor protein tyrosine phosphatase SHP-2 (SHP2), generating a gain of its function. Mutations in the PTPN11 gene are present in up to 50% of NS cases, followed by mutations in SOS1 and RAF1, KRAS, BRAF. NS and other clinically overlapping conditions such as NS with multiple lentigines (formerly called LEOPARD syndrome), cardiofaciocutaneous syndrome, or Costello syndrome, are caused by mutations in genes encoding proteins of the RAS-MAPKinases pathway. Because of this shared mechanism, these conditions have been collectively termed «RASopathies».

Objective: To characterize the patients with "RASopathies" Type Noonan Syndrome with PTPN11 mutation of the pediatric endocrinology consultation during the years 2016-2021

Results: We describe 4 patients with mutation in the PTPN11 gene: 3 men, 1 woman, with averages of: 37.6 weeks of gestational age, 2.7 kg of weight and 47.6 cm of height at birth. 100% had: palpebral ptosis, winged neck, pectum carinatum and short stature, 75% heart disease type subaortic stenosis and ventricular septal defect, and 33% hearing loss and alteration of genitalia. The mutations found in the PTPN 11 gene, all heterozygous were : in the males heterozygous and sporadic :Exon 7 c.836 A>G. pTYR:279cys, and c.417G>C (P.Glu139Asp) and p.Asn 308 Ser, c..923A>G, the female with mutation of c.417G>C (P.Glu139Asp) whose mother has SN.

Analysis: Although the diagnosis is clinical, this mutation according to the literature is found in 50% of patients, found in almost 60% of familial cases and in almost 40% they are sporadic. We found the mutation the PTPN11 gene in all our patients with NS, and 75% sporadic and 25% familiar. There is a phenotype-genotype correlation and they should be monitored for predisposition to malignancy

Conclusion: It is essential that physicians involved in the care of these patients are familiarised with their manifestations and clinical follow –up, especially due to predisposition to malignancy.