Noonan syndrome: Structural abnormalities of the mitral valve causing subaortic obstruction

Among 41 consecutive children with classic Noonan syndrome, 27 patients (66%) presented cardiac anomalies. Eight patients (19.5%) had a congenital anomaly of the mitral valve consisting of 5 with partial atrioventricular canal defect and 3 with anomalous insertion of the mitral valve on the ventricular septum. Five patients (12%) presented with a significant left ventricular outflow tract obstruction caused by the anterior leaflet of the mitral valve: two cases with atrioventricular canal and three cases with isolated anomalous insertion of the mitral valve. Echocardiography is the best tool for the diagnosis. Cardiac defects of patients with Noonan syndrome may be explained on the basis of anomalies of the extracellular matrix involving cardiac valves including the mitral valve.Conclusion In children with Noonan syndrome and left ventricular hypertrophy a careful echocardiographic assessment of the mitral valve should reveal those in whom the left ventricular outflow tract obstruction is anatomical in nature.     

Cardiovascular changes in children with mucopolysaccharide storage diseases and related disorders – clinical and echocardiographic findings in 64 patients

Cardiovascular abnormalities were evaluated in 64 children aged between 1 year 9 months and 25 years with mucopolysaccharidoses (MPS) and related disorders. A heart murmur was heard in 18 patients, but in only 6 was it characteristic for specific valvular lesions. Echocardiography was performed in 63 children. In one girl cardiac lesions were diagnosed on autopsy. In 46 patients (72%), valvular lesions and/or different types of cardiomyopathy were detected. There were no characteristic changes for different types of MPS. In the majority of children in whom dermatan sulphate accumulated, cardiac involvement was the most frequent (88%) and severe. The most common lesion, regardless of MPS type, was thickening of the mitral valve (66%), with regurgitation or stenosis in 28 (44%). Aortic valve thickening was detected in 17 patients (27%), asymmetric septal hypertrophy or hypertrophic cardiomyopathy in 18, congestive cardiomyopathy in 1 and endocardial thickening in 13 patients. Cardiac involvement was less frequent in children with Sanfilippo disease. Two or more echocardiographic examinations were performed in 23 patients. In 19 of them (83%) cardiac changes were more severe during the second examination. One 7-year-old boy with Hunter disease underwent successful mitral valve replacement. Conclusions Cardiac involvement is present in most patients with MPS although there are few clinical signs and symptoms. The most common and severe changes are in Hurler, Hunter, Maroteaux-Lamy and I-cell disease, rarely in Sanfilippo disease. Mitral valve deformation is most frequent in all patients. The cardiac lesions are progressive. Received: 15 March 1997 / Accepted: 20 January 1998     

Mitral valve prolapse syndrome in children with Duchenne's progressive muscular dystrophy.

Myocardial function was evaluated prospectively by noninvasive methods in 20 boys with clinical, biochemical, muscle biopsy, and electromyographic evidence of Duchenne's progressive muscular dystrophy. Auscultatory evidence of a nonejection systolic click suggested mitral valve prolapse (MVP) syndrome in seven patients. Phonocardiography disclosed that the click was mid-systolic in four patients and early in three. Echocardiographic features consistent with this diagnosis were identified in all seven patients and in an additional four. One of these had an apical pansystolic murmur, suggestive of mitral regurgitation, whereas in the other three, prolapse of the mitral valve was "silent". Echocardiographic findings included an abrupt midsystolic, posterior motion (greater than 3 mm beyond the CD line) in five patients, multiple sequence echoes in six, and posterior coaptation of the mitral valve near the left atrial wall in six. The features most characteristic of MVP syndrome was a smooth, pansystolic, anteriorly concave (hammock-like) posterior motion deviating more than 3 mm beyond the CD line. Among the remaining nine patients who did not have echocardiographic evidence of prolapsing mitral valve, none had an early, middle or late nonejection systolic click or a heart murmur, although four patients in this group had moderate to severe scoliosis. These observations document of occurrence of MVP syndrome in children with Duchenne's muscular dystrophy and indicate that its prevalence is high. We speculate that prolapse of the mitral valve in these patients is an expression of the underlying cardiomyopathy characteristic of Duchenne's muscular dystrophy rather than an isolated, dystrophic involvement of the mitral valve leaflets.     

What is the True Frequency of Carditis in Acute Rheumatic Fever? A Prospective Clinical and Doppler Blind Study of 56 Children with up to 60 Months of Follow-Up Evaluation

BACKGROUND: This study aimed to evaluate prospectively clinical and echocardiographic findings of patients who had rheumatic fever with and without clinical features of cardiac involvement. METHODS: For this study, 56 consecutive patients (mean age, 11.4 years) with acute rheumatic fever diagnosed according to the 1992 modified Jones criteria were evaluated at diagnosis, after 3 and 6 months, then at 2 and 5 years. All assessments were performed blindly and included physical and cardiac examination, electrocardiogram, chest X-ray, and two-dimensional color-flow Doppler echocardiography. RESULTS: Initial clinical carditis was observed for 27 patients (48.2%), all of whom had positive echocardiographic abnormalities. Echocardiographic abnormalities were observed in 11 patients who had arthritis or chorea presentation without initial clinical carditis. Persistence of the abnormalities was observed at a late follow-up evaluation in 72.7% of the cases. Sydenham's chorea was present in 8 patients with clinical carditis and in 10 without this disorder, 8 of whom had echocardiographic abnormalities. CONCLUSION: Patients who had acute rheumatic fever without clinical signs of carditis showed acute and late follow-up echocardiographic abnormalities suggestive of cardiac involvement. Clinicians should be attentive for the presence of cardiac involvement among patients with chorea.     

Prenatal Diagnosis of Severe Aortic Stenosis

We sought to identify echocardiographic markers that might be useful for managing fetuses with significant aortic stenosis. The study was a retrospective review of fetal echocardiographic studies and postnatal outcomes of all fetuses diagnosed with significant aortic stenosis who did not have a hypoplastic left ventricle on the initial echocardiogram. Where possible, fetal echocardiographic measurements included the aortic, mitral, pulmonary, and tricuspid valve annulus sizes; left ventricular dimensions and volume; septal and left ventricular wall thicknesses; and echocardiographic Doppler interrogation of the left heart and oval fossa. Observations also included an assessment of ascites, pericardial effusion, and endocardial fibroelastosis. Prenatal measurements were compared to postnatal outcomes. Four patients (group 1) had either clinically successful relief of their aortic obstruction (n= 3) or required no intervention (n= 1). Five fetuses evolved to the hypoplastic left heart syndrome (group 2). These infants demonstrated little or no growth in left ventricular, aortic valve, or mitral valve dimensions on serial examination. They also more often exhibited mitral stenosis, severe restriction of interatrial shunting, and early to mid second trimester left ventricular dilatation. Serial measurements of fetal cardiac size and function are helpful for predicting the postnatal outcome of fetuses with aortic stenosis.     

A post-streptococcal pathogenesis in children with tic disorders is suggested by a color Doppler echocardiographic study.

BACKGROUND: A post-streptococcal autoimmune mechanism, similar to that of rheumatic fever or Sydenham's chorea, has been hypothesized in some cases of neuropsychiatric disorder (tics and/or obsessive-compulsive disorders). A few studies on the involvement of other organs, outside the central nervous system, have been performed in these patients. AIM: To evaluate a possible post-streptococcal pathogenesis in the children affected by tic disorders and showing sign of streptococcal exposure. METHODS: A case-control study was performed at the Outpatient Division of the Child Neurology and Psychiatry, and Paediatrics Departments of the University "La Sapienza" of Rome, from September 1, 2000, to February 28, 2005. Forty-eight subjects affected by tic disorder, aged 4-16 years, with signs of a recent or intercurrent exposure to streptococcal antigens, and 18 age-matched patients affected by tic disorder but without evidence of streptococcal exposure were examined by Color doppler echocardiography. RESULTS: The rate of echocardiographic abnormalities was significantly higher (p<0.001) in the patients with sign of streptococcal exposure. In 28 out of 48 patients (58.3%), the color Doppler echocardiography showed abnormalities: 26 patients (54,3%) had a mitral regurgitation, 1 (2%) a mitral valve prolapse and finally 1 (2%) showed a kinking of the anterior mitral valve leaflet. In the control group, four children (22.2%) showed a mitral regurgitation. All of these abnormalities were not hemodynamically significant, and in many cases decreased with time. CONCLUSIONS: The higher rate of echocardiographic abnormalities observed in patients with tic disorder and exposure to group A beta-haemolytic streptococcal antigens, together with their decrease with time, suggest a post-streptococcal pathogenesis.     

Cardiac involvement in Coffin-Lowry syndrome

Coffin-Lowry syndrome is an X-linked recessive syndrome of mental retardation, characteristic facies and skeletal anomalies. In one patient with the syndrome, we observed early recurrent episodes of congestive heart failure with intercurrent normalization and the late development of mitral insufficiency due to annular dilation and congenital abnormalities of the valve apparatus. This unusual course of cardiac involvement, the non-adaptation of the left ventricular contractility to the aggravation of the mitral insufficiency and the postoperative persistence of the ventricular dysfunction, underline the possible role of an associated primary myocardial disease. This clinical observation demonstrates clearly that a mitral valve malformation can occur in patients with the syndrome, but also the role of a dilated cardiomyopathy, which can be secondary to the mitral regurgitation, but is more likely a myocardial disorder occurring as part of the syndrome.     

Marfanoid children. Etiologic heterogeneity and cardiac findings

The clinical, cardiac, and echocardiographic test results of 20 children with marfanoid features are reviewed. Fifteen were diagnosed as having Marfan syndrome, two had "possible" Marfan syndrome, and three had other diagnoses. On first evaluation, eight patients with Marfan syndrome (53%) had mitral regurgitation and none had aortic regurgitation. Echocardiography showed aortic root enlargement in 12 (80%) of 15 patients and mitral valve prolapse in 12 (80%) of 15. None had a normal echocardiogram. At follow-up examination, one patient had developed aortic root enlargement, and one patient, mitral valve prolapse. Thus, although aortic root enlargement is usually present in early childhood in patients with Marfan syndrome, it is not considered specific because in this study it also occurred in one child with Alport's syndrome and in one with marfanoid features. Four patients with aortic root enlargement were treated with propranolol and their echocardiograms showed no further increase in the aortic root diameter for several years. We recommend echocardiography in the diagnosis and routine management of children in whom Marfan syndrome is suspected.     

儿童多发性大动脉炎合并心功能不全5例病例系列报告

目的 总结儿童多发性大动脉炎（TA）合并心功能不全的临床特征。方法 回顾性分析首都儿科研究所附属儿童医院2013年1月至2019年12月确诊的TA合并心功能不全患儿的临床资料。结果 共5例患儿进入本文分析,均为女性,起病年龄2~14岁。以心脏症状起病4例,包括胸闷、心悸、头晕、乏力、多汗。血管杂音5例,脉弱/无脉4例,高血压4例。5例均合并心脏瓣膜受累,3例为多瓣膜受累。二尖瓣关闭不全4例;主动脉瓣关闭不全3例,其中2例伴有升主动脉扩张;三尖瓣关闭不全3例;冠状动脉扩张3例。5例临床分型均为Ⅲ型（混合型）。4例接受糖皮质激素和（或）免疫抑制剂治疗,2例接受TNF-α拮抗剂英夫利昔单抗治疗。1例失访,4例随访6~48个月,患儿症状均有不同程度好转,除已有不可逆心脏损伤外,炎性指标均正常,无新发病灶。1例合并顽固高血压,拟接受外科手术治疗。结论 TA患儿应定期行心脏超声检查以及早发现心脏病变,、及时干预。以心脏症状起病的患儿,除应考虑原发性心脏疾病,还应警惕TA累及心脏的可能。TA合并心功能不全患儿中,主动脉和肾动脉出现血管狭窄者,多合并高血压。     

Cardiovascular changes in children with mucopolysaccharide disorders

The aims of this study were to evaluate cardiac involvement, assess risk factors and mortality, and define the outcome of cardiac abnormalities with age in the different types of mucopolysaccharidoses (MPS). The echocardiograms of 99 patients with MPS, aged 1-24 y (median age 10.3 y) were reviewed between 1978 and 2000. Mitral regurgitation (MR) was detected in 29 patients (29%). MR was more frequent in types IH [ n = 11 (38%)], II [ n = 10 (24%)] and III [ n = 4 (20%)]. Sixteen patients (16%) developed aortic regurgitation (AR), seen mostly in types II [ n = 9 (56%)] and IV [ n = 4 (24%)]. AR and/or MR was detected in 37 patients and 8 had both abnormalities of borderline significance (odds ratio 2.95, 95% confidence interval 1.0-8.85, p = 0.05). Of 99 patients, 47 had a normal study on their first echocardiogram, whereas only 7 had a normal study on subsequent echocardiograms. Fifty-four (54%) had a single echocardiogram. Of these, 27 (50%) were abnormal and 27 normal. Forty-five patients had more than one echocardiogram, of which 25 (56%) were abnormal and 20 normal. In 13/20 (65%) a cardiac abnormality developed on a subsequent echocardiogram which was statistically significant ( p = 0.002). Overall mitral and aortic valve abnormalities showed a positive association with age. Univariate analysis of risk factors showed that increasing age, MPS I and ejection fraction were significant risk factors for death. However, left ventricular hypertrophy, mitral valve abnormalities and type II MPS were not significant risk factors for death, with borderline significance for aortic valve abnormalities.

Conclusion: This study demonstrates the evaluation of ventricular function, which is a significant risk factor for death, along with increasing age and MPS I, and outlines the borderline significance of aortic valve abnormalities, which has not been mentioned in previous studies. It also shows that mitral valve lesions, commonly seen in MPS, were not a significant risk factor for death. The results emphasize the importance of performing serial echocardiograms in patients with MPS to assess ventricular function and the progression of cardiac abnormalities with age.     

Gaucher's disease with mitral and aortic involvement: Echocardiographic findings

Summary Cardiac involvement in Gaucher's disease has been reported in only a few patients, mostly adults with pericardial changes. We describe findings in two siblings with Gaucher's disease, aged 15 and 9 years respectively, in whom mitral and aortic valve lesions were evaluated by auscultation and echocardiography. In both cases the mitral and aortic valves were thick and restricted in motion. Continuous Doppler echocardiography revealed significant mitral regurgitation and mitral stenosis. At the aortic valve level there was a systolic pressure gradient. Echocardiographic investigation of patients with suspected cardiac involvement with Gaucher's disease is recommended.     

The clinical course and echocardiographic features of Marfan's syndrome in childhood

The clinical and echocardiographic manifestations in 25 patients with Marfan's syndrome diagnosed during infancy and childhood (mean [+/- SD] age, 8.1 +/- 4.8 years; range 0 to 16 years) were evaluated. Twenty-one patients (84%) had a midsystolic click, 11 patients (44%) had mitral regurgitation (MR), and five patients (20%) had combined MR and aortic regurgitation (AR). Echocardiography demonstrated mitral valve prolapse in all 25 patients, aortic root dilatation in 20 patients (80%), AR in seven patients (28%), and aortic aneurysm in five patients (20%). During the follow-up period (mean, 5 +/- 4.5 years), progressive AR and aortic aneurysm were documented in four patients, progressive MR in three patients, and progressive aortic root dilatation in two patients. Five patients (22%) died during the follow-up period. Among patients with a positive family history of Marfan's syndrome, MR was less frequent as compared with sporadic cases (29.4% vs 75%, respectively). Progressive cardiovascular involvement was more frequent among patients diagnosed before 10 years of age compared with those diagnosed later (60% vs 12.5%, respectively). Cardiovascular involvement was a common feature of childhood Marfan's syndrome, causing significant morbidity and mortality. Sporadic cases and children diagnosed before 10 years of age represented a particularly high-risk group.     

A clinical profile of mitral valve prolapse syndrome

Clinical, radiologic, electrocardiographs and 2-dimensional echocardiographic findings of fifty cases of mitral valve prolapse syndrome attending the Pediatric Cardiology clinic of I.C.H. and Childrens Hospital, Medical College, Kottayam over a period of ten years from 1980-1989 are presented. Mitral valve prolapse syndrome (MVPS) accounted for 2% of cardiac problems attending our pediatric cardiology clinic. Isolated MVPS constituted 64% of the cases. The common causes of secondary MVPS were Marfan Syndrome-18%, Atrial Septal Defect-10% and Rheumatic fever-8%. Associations of MVPS included Pectus excavatum (8%), Isolated arachnodactyly (2%) and Straight back syndrome (2%). 2-D echocardiogram demonstrated prolapse of both leaflets of Mitral valve in 44%, Isolated posterior mitral valve leaflet prolapse in 32% and Isolated anterior mitral valve leaflet prolapse in 24% of cases. No complications were seen during follow up.     

Echocardiographic evaluation of mitral valve in patients with pure rheumatic mitral regurgitation

The aims of this study were to evaluate the structure of the mitral valve (MV) and subvalvar apparatus in patients with rheumatic mitral regurgitation (MR) by echocardiography and to compare the differences in morphologic abnormalities between subgroups of patients with and without mitral valve prolapse (MVP). Two-dimensional and color Doppler echocardiographic examinations were performed in 20 consecutive patients with isolated rheumatic MR and in 15 healthy subjects as controls. Annular diameter, left ventricular end-diastolic dimension, anterior leaflet length, and both leaflet thicknesses were greater in MR than those of controls. Anterior leaflet and chordal lengths were greater in severe MR than in mild or moderate MR. Sixty percent of rheumatic MR patients had nodules on the body or tip of the anterior mitral leaflet and MR was more severe in these patients. Nine of 20 patients (45%) had MVP. MR was more severe in the patients with MVP than those without prolapse. Rheumatic etiology should be suspected in patients with MR when irregular focal thickening of MV, relatively immobile posterior leaflet, eccentric regurgitant jet, and anterior MVP are found in echocardiographic study.     

Mitral valve disease in Marfan's syndrome.

Cardiovascular disease in Marfan''s syndrome presenting in childhood affects the mitral valve more often than the aortic valve or the aorta, as in adults. Early evaluation of the cardiovascular system is necessary for any child in whom Marfan''s syndrome is suspected.     

Use of Doppler Echocardiography to Support the Decision to Discontinue Secondary Prophylaxis for Patients With Rheumatic Fever and Normal Cardiac Auscultation

Secondary prophylaxis remains the safest way to prevent or minimize heart valve damage in patients with rheumatic fever. However, criteria to determine the duration of prophylaxis have not been well established. This study aimed to evaluate the clinical and Doppler echocardiographic profile of patients with rheumatic fever and a normal clinical examination at least 5 years after the first episode and to discuss the contribution of Doppler echocardiography in supporting the decision to discontinue secondary prophylaxis. An observational longitudinal study analyzing 183 patients with rheumatic fever and a normal clinical examination 5 years or more after the initial attack was conducted. The patients underwent Doppler echocardiography to study the severity of mitral or aortic valvular disease. Of the 183 patients, 77 (42 %) had clinical carditis. Subclinical chronic heart disease occurred for 79 % of the patients with previous clinical carditis and for 25 % of the patients without clinical carditis. Of the 35 patients with previous clinical carditis who were in the period of discontinued prophylaxis, residual valvular heart disease was observed in all, whereas of the 62 patients without clinical carditis, only 27 % showed residual valvular heart disease. Considering Doppler echocardiographic criteria, prophylaxis would be continued for 13 (34 %) of the patients with previous clinical carditis and for only 2 (3 %) of those without clinical carditis. Return of cardiac auscultation to normal is not always accompanied by return of Doppler echocardiographic findings to normal. Criteria regarding Doppler echocardiographic findings and valve morphology should be evaluated by the time secondary prophylaxis is discontinued. However, further studies are needed to demonstrate whether prolonged prophylaxis provides any benefit to patients with persistent echocardiographic findings.     

Subclinical hypothyroidism and Down's syndrome; studies on myocardial structure and function

Background: The management of subclinical hypothyroidism (SH) is still controversial, as the benefit to risk ratio of prolonged L-thyroxine therapy is not clear cut. Some authors have shown abnormalities of myocardial function and structure in adults with SH, which could be reversed by L-thyroxine therapy. As SH frequently affects children with Down''s syndrome (DS), and almost one half of these are affected by congenital heart disease, a concomitant SH related impairment of cardiac function might further compromise their clinical condition. Aims: To establish whether SH influences myocardial structure and function in children with DS. Methods: Sixteen children with DS and untreated SH and 25 matched euthyroid controls with DS underwent echocardiographic analysis of left ventricular mechanics and tissue characterisation. Results: None of the 16 patients had myocardial impairment. Conclusion: Results suggest that children with DS who have SH are not at risk of cardiac disease. Clinicians should consider these data in the management of SH, as the benefit to risk ratio of prolonged L-thyroxine therapy is not clear cut.     

Reversible mitral valve prolapse and mitral regurgitation in children with Graves' disease

An association between mitral valve prolapse (MVP) and hyperthyroidism has been described in adults. However, the long-term prognosis when associated with significant mitral regurgitation remains unclear. Three consecutive children with Graves' disease were found to have a loud mitral regurgitation murmur (grade III/VI) and echocardiographic evidence of MVP with moderate mitral regurgitation. The cardiac manifestations included palpitations, exertional dyspnea, and exercise intolerance. The electrocardiograms at presentation were sinus tachycardia in all cases. All had hyperthyroidism and positive thyroid antibodies. Exophthalmos occurred in two and appeared later than the cardiac symptoms in one. The cardiac murmur disappeared in all patients when antithyroid agents controlled the hyperthyroidism. Follow-up echocardiography showed normal in one and MVP with mild mitral regurgitation in two. We conclude that MVP and significant mitral regurgitation can occur in children with hyperthyroidism, especially those with Graves' disease. The prognosis is good after adequate medical control of the hyperthyroidism.     

Mitral valve replacement in the neonate: A report of two cases

Summary Mitral valve replacement was performed in two critically ill neonates with severe mitral stenosis and regurgitation. Both patients had coexisting severe aortic stenosis previously treated by transventricular aortic valve dilatation. Preoperative echocardiography showed a mitral annulus measuring between 11 and 12 mm in diameter—too small for any of the commercially available free-standing valve prostheses. Accordingly, the porcine valve from a commercially available 12-mm external-valved conduit was removed and sutured into position. The function of the valve was satisfactory in both cases and cardiopulmonary bypass was discontinued easily with a good cardiac output established in both. Both patients died—one at 20 h and one 36 h after surgery. In each case, the immediate cause of death was acute bleeding secondary to preexisting hepatic failure and depletion of coagulation factors. At autopsy, both prostheses had been correctly placed and were competent. Left ventricular outflow tract obstruction secondary to strut imposition was not evident. Both patients were very ill preoperatively. Although neither patient survived mitral valve replacement, we were encouraged by the relative hemodynamic improvement in the immediate postoperative period. We believe that prosthetic valve replacement could become a viable therapy for the neonate with severe mitral valve abnormalities.     

Echocardiographic studies of left ventricular disease in Ullrich-Noonan syndrome.

Echocardiography has been used for cardiovascular evaluation of individuals and families with Ullrich-Noonan syndrome. Previously undiagnosed left ventricular disease has been found as a discrete lesion or in association with other cardiac abnormalities. This raises the estimated frequency of heart disease in the Ullrich-Noonan syndrome to about 50%. Since left ventricular disease in this syndrome may not be entirely typical of asymmetric septal hypertrophy, caution should be exercised in the echocardiographic diagnosis. To date, one notable difference between the echocardiograms in these patients and other patients with asymmetric septal hypertrophy is the absence of systolic anterior motion of the mitral valve. Since the most common cardiac lesion the the Ullrich-Noonan syndrome is pulmonary stenosis, the potential for septal thickening produced by severe pulmonary stenosis must also be taken into account.