Mutation and Phenotypic Spectrum of Patients With RASopathies

Area of Science:

• Medical Genetics
• Pediatric Endocrinology
• Dermatology

Background:

• Noonan syndrome and related RASopathies are a group of genetic disorders.
• These conditions present with a range of clinical manifestations.
• Accurate diagnosis and understanding genotype-phenotype correlations are essential for patient management.

Purpose of the Study:

• To investigate the shared and distinct clinical features of Noonan syndrome and related RASopathies.
• To analyze the mutation spectrum and genotype-phenotype correlations in affected individuals.
• To improve diagnostic accuracy and clinical suspicion for these conditions.

Main Methods:

• Retrospective review of 30 patients diagnosed with Noonan syndrome or related RASopathies over six years.
• Comprehensive clinical phenotype evaluation.
• Genetic testing including PTPN11 sequencing and next-generation sequencing for molecular diagnosis.

Main Results:

• Noonan syndrome was confirmed in 22 patients, with cardiofaciocutaneous syndrome in 5, and Noonan syndrome-like disorder with loose anagen hair in 3.
• PTPN11 gene mutations were identified in 57.8% of patients with confirmed molecular diagnoses.
• Common phenotypes included developmental delay, cardiac defects, ectodermal abnormalities, and coarse facial features.

Conclusions:

• Noonan syndrome and RASopathies should be suspected in patients presenting with short stature, cardiac defects, and characteristic facial dysmorphism.
• Sparse, slow-growing hair is a key feature of Noonan syndrome-like disorder with loose anagen hair, linked to SHOC2 mutations.
• Early recognition and genetic confirmation are vital for effective management of these complex genetic disorders.