| Popis: |
Introduction: RASopathies are a set of phenotypically overlapping syndromes caused by mutations in genes that play a role in the RAS/MAPK pathway involved in development through growth factors. The most common is Noonan Syndrome (NS) which is an autosomal dominant genetic disorder, of low prevalence and which in 50% of cases is associated with variants in the PTPN11 gene. Clinical manifestations are short stature, dysmorphic facial features, congenital heart defects, most commonly pulmonary valve stenosis, typical chest, and cryptorchidism. Results: We describe 4 patients with RASopathy Noonan syndrome due to alteration in the PTPN11 gene: 3 males, and 1 female, with an average gestational age of 37.6 weeks, 2.9 kg of weight, and 45.5 cm of height at birth. 100% had: palpebral ptosis, winged neck, pectum carinatum, and short stature, 75% had heart diseases such as subaortic stenosis and ventricular septal defect, and 33% had hypoacusis and altered genitalia. The genetic variants found in the PTPN 11 gene, all heterozygous were: in the sporadic males: Exon 7 c.836 A>G. pTYR:279cys, and c.417G>C (p. Glu139Asp) and p.Asn 308 Ser , c..923A>G heterozygosis. The female with a variant in c.417G>C (p. Glu139Asp) whose mother has SN. Analysis: We found the PTPN11 gene variant in all our patients with NS, 75% being sporadic and 25% familial. Although the diagnosis of Noonan syndrome is clinical, this variant according to the literature is found in 50% of patients, in almost 60% of familial cases, and in almost 40% sporadic. There is a phenotype-genotype correlation in these patients and it is suggested that they should be monitored for predisposition to malignancy. Conclusions: It is essential to typify the clinical and genetic alteration in patients with RASopathies so that physicians involved in the care of these patients are familiar with the diagnosis, genetic variant, manifestations, and clinical follow-up, especially because of their predisposition to malignancy |
