IMPE Abstracts

The Noonan syndrome (NS) is part of the rasopathies. Rasopathies are autosomal dominant and recessive disorders due to mutations in genes encoding components or regulators of the RAS/mitogen-activated protein kinase (MAPK) signal transduction pathway, which is essential for cell cycle differentiation, growth, and senescence This syndrome presents three cardinal characteristics: distinctive facial features, postnatal short stature, and cardiac abnormalities. NS coexists with minor signs such as cryptorchidism, delayed puberty, bleeding disorders, lymphedema, chest abnormalities, skin disorders, varying degrees of neurocognitive delay and predisposition to myeloproliferative disorders.

Results: A total of 11 patients (6 men and 5 women) were diagnosed with exome sequencing by the pediatric endocrinology service of Medellín, Colombia in the years 2021 to 2022; all had been referred for short stature. The earliest diagnosis was at one year of life and the latest diagnosis was at 17 years. The most frequently altered gene was PTPN11 in 7 patients, and the most prevalent mutation was p.Asn308Asp, in the PTPN11 gene in 3 cases. This is also one of the most prevalent mutations in the European and Argentina population. Other genes found were SHOC, LZTR1, NRAS, KRAS. 36.3% had a short stature mother and 18% had a short stature affected father. In addition, 100% have height and weight according to their gestational age at birth and 18.1% were premature. The clinical manifestations had the following order of presentation: 100% of the patients had short stature, low-set ears at 81.8%, short neck at 72.2%, downward palpebral fissures at 63.6%, hypertelorism at 45.4%, neurodevelopmental delay 45.4%, heart disease at 45.4%, cryptorchidism at 36.3%, cubitus valgus at 27.2%, prominent forehead at 18.1%, telemamilla at 18.1%, syndactyly, language disorder, umbilical hernia, clinodactyly, spina bifida, renal alteration, and bronchiectasis in 9% of cases. Growth hormone treatment for short stature was administered in 27.2% of these patients.

Conclusion: NS has a prevalence of one in 1,000-2,500, being a frequent disorder in our population. This syndrome requires multidisciplinary management due to short stature, increased risk of tumors and associated heart disease. Diagnosis can be made on the basis of clinical features, but may be missed in mildly affected patients. Molecular genetic testing can confirm diagnosis in 70% of cases and has important implications for genetic counseling. The initiation of growth hormones continues to be discussed due to the risk of increased tumors in these patients and the lack of long-term studies that support treatment.