Biventricular Hypertrophy and Valvular Pulmonary Stenosis in Adult Patient with Noonan Syndrome: A Rare Case

41-year-old Javanese male presented with chief complaint shortness of breath. His Body Mass Index (BMI) was 18,3. He had an oval-shaped face with a short neck, thin hair, and prominent nasolabial fold. Echocardiography showed biventricular hypertrophy alongside pulmonary valve stenosis, pulmonary regurgitation and minimal pericardial effusion. We reported a case of a patient with typical characteristics of Noonan syndrome (NS) such as pulmonary valve stenosis accompanied by biventricular ventricular hypertrophy and its typical face who survived through adulthood. Case Report Biventricular Hypertrophy and Valvular Pulmonary Stenosis in Adult Patient with Noonan Syndrome: A Rare Case Tinton Pristianto1, Rosi Amrilla Fagi1,2 Faculty of Medicine, Universitas Airlangga. Department of Cardiology and Vascular Medicine, Dr. Soetomo General Hospital.


Introduction
Noonan syndrome is a genetic disorder that is often accompanied by multiple congenital abnormalities.
Noonan syndrome incidence is reported to be approximately one in 1,000 and one in 2,500 [1] . Some of the symptoms and signs include congenital heart disease, short stature, short and wide neck, sternal deformity, developmental abnormalities, cryptorchidism, increased bleeding risk, and distinct facial features 2 . Noonan syndrome phenotypes in children have been thoroughly studied previously, but its prevalence in adults is small and rarely known. Dr. Noonan reported that Noonan syndrome occurred in 56 adults aged 21-59 years [3] . A study by Shaw DKK that reported medical problems in children and adults with Noonan syndrome aged 12-71 years who were followed for 12 years found that 31% of patients have heart problems 4 .
More than 80% of Noonan syndrome patients have abnormalities in cardiovascular system 5 .
Cardiovascular abnormalities that often occur in Noonan syndrome are pulmonary stenosis 6 and hypertrophic cardiomyopathy (HCM), which are dominant in interventricular septum and left ventricle area [7] . Pulmonary stenosis is the most common heart defect, where pulmonary valve dysplastic occurs in 25-35% of patients 4 .
Hypertrophic cardiomyopathy is found in 20% of Noonan syndrome patients which is usually caused by a RAF19 mutation. It is important for adults with Noonan syndrome to have regular heart check [5] . Hypertrophic RV was found (RVWT 1.0 cm). There was a minimal inferior (0.7 cm) pericardial effusion.

Discussion
In 1962, Jacqueline Noonan, a pediatric cardiologist, identified nine patients whose faces were very similar, had short stature, significant chest deformities, and pulmonary stenosis [10] .
Noonan Syndrome was named after Dr. Noonan because she was the first person to report that this condition occurs in both sexes, is linked to normal chromosomes, and includes congenital heart defects [5] . Noonan syndrome is a relatively common non-chromosomal syndrome similar to Turner's syndrome phenotype and is associated with cardiovascular malformations [11] . It will be challenging to identify Noonan syndrome in individuals with mild symptoms. The incidence is one in 1,000 to 2,500 live births for severe phenotypes, whereas mild clinical phenotypes might occur more frequently (about 1%) [12] .
Among the genes that are mutated in people with  [14] . Patients with Noonan syndrome who have a missense mutation in PTPN11 are more likely to have pulmonary stenosis and ASD and are less likely to have hypertrophic cardiomyopathy (HCM) than patients without PTPN11 mutations [15] . Patients who have SOS1 mutation are also more likely to have pulmonary stenosis than those who do not have SOS1 or PTPN11 mutations [16] . Previous studies also found that 80-95% of patients with RAF1 mutations will have HCM [5] . Bleeding risk and myelomonocytic leukemia are also found in Noonan syndrome patients with PTPN11 mutation [13] . KRAS gene mutation provides a clinical phenotype of developmental delay [17] . older adults, nasolabial folds will appear more visible than ordinary people of their age and their skin will appear to be transparent and thin. The hair will appear to be thin and sometimes curly, and sometimes their eye colors are blue or turquoise, which are not similar to their family's. [ 5] In this case,