ESPE Abstracts

Introduction: Noonan syndrome (NS) is a dominant autosomal genetic disorder caused by a mutation in the RAS–MAPK pathway. The clinical manifestations usually reported in NS are short stature, pulmonary stenosis, cryptorchidism, hematological abnormalities and dysmorphic face.

Patients and Methods: We studied the demographic characteristics, clinical presentations and treatment patterns associated with NS, integrating genetic results in 21 patients aged between 18 months and 23 years.

Results: The average age of diagnosis is 7.33 years, emphasizing the challenges in early recognition. Among the cases, there was a male predominance, with 13 males and 8 females, indicating potential gender-specific considerations. Dysmorphic facial features were universally observed in all cases, highlighting the diagnostic importance of facial phenotype in NS. Skeletal abnormalities were prevalent, with 15 out of 21 cases exhibiting deformities. Mental retardation is reported in 10 cases, underscoring the cognitive impact of the syndrome. Cardiac involvement was a common finding, with 17 out of 21 cases presenting with heart disease, particularly pulmonic stenosis and persistent arterial canal. Cryptorchidism was identified in 10 out of 13 males, emphasizing the importance of assessing genitourinary abnormalities in male patients. Hearing deficits were present in 5 out of 21 cases, adding to the spectrum of associated clinical features. Additionally, monocytosis was observed in three cases, and these individuals subsequently developed juvenile myeloid leukemia. Hyperthyroidism was noted in three cases, shedding light on the potential endocrine complications associated with NS. Six out of the 21 cases were treated with growth hormone, indicating a therapeutic approach to address growth-related concerns in select individuals with NS. Genetic analysis revealed PTPN11 mutations in three cases and one CBL mutation, providing insights into the underlying molecular basis of NS. These genetic findings contribute to the expanding understanding of the genetic landscape associated with the syndrome. Notably, 95% of the cases exhibited short stature, underscoring the prevalence of this characteristic in NS. This finding highlights the importance of early recognition and intervention to address growth-related concerns in affected individuals.

Conclusion: This comprehensive analysis, integrating both clinical and genetic data, provides valuable insights into the clinical and molecular heterogeneity of NS. It emphasizes the importance of a multidisciplinary approach for accurate diagnosis, management, and surveillance of associated comorbidities, while also paving the way for further research to enhance our understanding of this complex genetic disorder and optimize patient care.