Biventricular Hypertrophic Cardiomyopathy With Right Ventricular Outflow Tract Obstruction Associated With Noonan Syndrome in an Adult

Abstract

oonan syndrome is one of the most common nonchromosomal syndromes frequently accompanied by cardiovascular malformations. 1 The major cardiovascular defects are valvular pulmonary stenosis, commonly due to a dysplastic valve, 2,3 and hypertrophic cardiomyopathy (HCM), which predominantly affects the interventricular septum and left ventricle. [4][5][6][7][8][9] We report an adult case of Noonan syndrome with biventricular HCM accompanied by isolated right ventricular outflow tract (RVOT) obstruction without valvular abnormalities. To the best of our knowledge, these conditions are regarded as rather uncommon manifestations of cardiac defects in adults with Noonan syndrome. Case ReportA 42-year-old man with dyspnea and palpitation on exertion was referred from his local hospital for further cardiac examination in April 2000. Heart murmur and electrocardiographic abnormalities were first noticed when he was 10 years of age, and he had experienced mild dyspnea on exertion since that time. On admission, blood pressure was 118/68 mmHg and pulse was regular at 72 beats/min. Neither mental retardation nor sexual infantilism was observed. He was of short stature (152cm; < mean -3.0 SD), had a short neck, a shield-like chest with widely spaced nipples, cubitus valgus (Fig 1A), and the characteristic facial traits of ocular hypertelorism and low-set posteriorly rotated ears ( Fig 1B). A grade 3 systolic ejection murmur was heard at the mid-left sternal border and S4 was heard at the apex. An electrocardiogram showed left axis deviation, P waves with high peaks in the inferior limb leads, and deep S waves over the precordial leads. Chest X-ray showed cardiomegaly with normal pulmonary vascularity. Laboratory tests revealed prolongation of the activated partial thromboplastin time (46.2 s; normal value, 24-37 s) and a somewhat deficient clotting factor 11 (61.2%; normal value, 75-137%) but without any hepatic dysfunction. The lymphocyte karyotype showed a normal male pattern.Transthoracic echocardiography (Fig 2) revealed biventricular hypertrophy with asymmetric septal hypertrophy. The hypertrophied septum bulged out into the outflow portion of the right ventricle, thus reducing the size of the right ventricular cavity and resulting in outflow obstruction. Transesophageal echocardiography (Fig 3) demonstrated far more pronounced hypertrophy in the interventricular septum than in the free wall of each ventricle and marked narrowing of the RVOT. The pulmonary valve was normal. Magnetic resonance imaging clearly demonstrated marked biventricular hypertrophy including that of the left ventricular free wall (Fig 4). Cardiac catheterization showed a pulmonary capillary wedge pressure of 11 mmHg, pulmonary arterial pressure of 22/12 (16) mmHg, RVOT pressure of 22/6 mmHg, right ventricle apex pressure of 70/6 mmHg, right atrial pressure of 6 mmHg, systemic arterial pressure of 110/70 (90) mmHg, and cardiac index of 1.44 L·min -1 · m -2 . A systolic pressure gradient of 48 mmHg was seen across the right ventricular outflow tract (F...

Massive Global Right Ventricular Hypertrophy with Both Fixed and Dynamic Obstruction and Pulmonary Valve Dysplasia

“…There is little data available to guide management of a case of diffuse intracavitary RV obstruction. In the isolated case of a patient with Noonan syndrome having a similar cardiac phenotype reported by Hayashi et al., the patient was managed successfully with beta blockade alone 13 . In the present case, in spite of beta blockade, the patient continues to be extremely symptomatic.…”

“…In the isolated case of a patient with Noonan syndrome having a similar cardiac phenotype reported by Hayashi et al, the patient was managed successfully with beta blockade alone. 13 In the present case, in spite of beta blockade, the patient continues to be extremely symptomatic. We hypothesize that in the present case, the patient's syncope resulted predominantly from RV preload dependence; any procedure achieving decreased RV work and thereby reducing hypertrophy might serve to improve diastolic performance.…”

“…With his hypothesized specific genetic background, the relatively mild pathologic stimulus provoked by the pulmonary valve gradient may have been sufficient to elicit a disproportionate hypertrophic response, resulting in the present phenotype. In this context, a single patient with Noonan syndrome having a combination of pulmonary valve dysplasia and hypertrophic cardiomyopathy leading to RVOT obstruction has been previously reported by Hayashi et al 13 …”

Adults with genetic syndromes and cardiovascular abnormalities: clinical history and management

“…Hypertrophic cardiomyopathy can progress in the adult with Noonan syndrome to right ventricular outflow tract obstruction due to septal hypertrophy, can be associated with severe pulmonary valve stenosis, or can evolve into a dilated form of cardiomyopathy. [223][224][225][226] Restrictive cardiomyopathy and constrictive pericarditis have been rarely reported. 226 -228 Idiopathic pulmonary hypertension has been reported in two adults and one female teenager with Noonan syndrome.…”

Significant biventricular obstruction in non-syndromic hypertrophic cardiomyopathy

“…However, most cases present early and this condition is rare in adults without a dysplastic pulmonary valve 1 2. It appears that biventricular HCM in young patients can initially be localised to only the RV 3.…”