Abstract
Background
Noonan syndrome is a rare genetic disorder. Typical cardiac involvement include pulmonary stenosis and hypertrophic cardiomyopathy. We present the association of Noonan syndrome with familial non-hypertrophic cardiomyopathy with haemodynamic features of restrictive physiology.
Case description. A 30-year old male patient presented to the outpatient clinic with clinical symptoms of heart failure which was slowly progressive since age 20. He was found to have features of restrictive cardiomyopathy aged 12 years at the time when his mother was diagnosed with Noonan syndrome and restrictive cardiomyopathy.
On examination, his 1st and 2nd heart sounds were normal, however 3rd heart sound was present. Pulse was regular, 75 per minute, BP 110/70 mmHg. Chest was clear and saturation 98%.
Echocardiography showed small left ventricle (LV) with preserved ejection fraction (EF), borderline LV wall thickness (10-11 mm), restrictive filling pattern with mitral valve E/A ratio 4.2 and deceleration time 68 ms; dilated both atria; and pulmonary artery systolic pressure of 37 mmHg (Figure, panels A-C; F). Prominent late diastolic reversal flow was noted in hepatic veins (Panel D). LV longitudinal strain was borderline in absolute value (-18%) however demonstrated ‘apical sparing’ pattern (Panel E). The right ventricle was small in size with mild hypertrophy and dynamic function, but normal flow through pulmonary valve. Prominent diastolic reversal flow was also noted in superior vena cava.
Cardiac magnetic resonance confirmed echocardiographic findings and additionally demonstrated prominent trabeculations and myocardial crypts in the LV, small pericardial effusion; no signs of amyloidosis, myocardial infarction, infiltration or fibrosis.
Right heart catheterisation showed borderline pulmonary hypertension with a mean pressure of 25 mmHg, raised pulmonary artery wedge pressure 18 mmHg, normal pulmonary vascular resistance 1.9 WU, and a ‘square root sign’ (Panel G).
Patient underwent cardiopulmonary exercise testing, he stopped after 9 mins of Bruce protocol due to fatigue, reaching the Peak VO2 of 21.1ml/kg/min (49% of predicted value). No ST changes or arrhythmic events were noted.
Patient was diagnosed with primary (non-infiltrative) familial restrictive cardiomyopathy and discussed at multidisciplinary team meeting with recommendation of close follow-up for timing for heart transplantation. Meanwhile he was encouraged to continue treatment with ramipril and start regular physical activity.
Discussion
There are only few reports describing familial non-hypertrophic cardiomyopathy in patients with Noonan syndrome and none in their family members. We review typical clinical and diagnostic features of restrictive cardiomyopathy involving both ventricles and raise awareness of clinicians of primary familial restrictive cardiomyopathy as a possible cardiac manifestation in patients with Noonan syndrome and their immediate family members.
Abstract P645 Figure.
Tyrosyl phosphorylation of PZR promotes hypertrophic cardiomyopathy in PTPN11-associated Noonan syndrome with multiple lentigines
