Clinical Features, Image Analysis And Mutations Of Children Cardiomyopathy

Part I Clinical features and prognosis of children cardiomyopathyObjective:Cardiomyopathy is one kind of serious disease of children, which prognosis is poor, and survivors are often accompanied by myocardial dysfunction. This study was performed to summarize the clinical features and prognosis of children with cardiomyopathy.Methods:Collected the clinical data of 53 patients with cardiomyopathy diagnosed by Echo and cMRI in children’s hospital of chongqing medical university in recent 4 years,8 cases of hypertrophic cardiomyopathy (HCM),17 cases of dilated cardiomyopathy (DCM),11 cases of restrictive cardiomyopathy (RCM),10 cases of endocardial fibroelastosis (EFE),7 cases of left ventricular noncompaction (LVNC), the morbidity and clinical characteristics were summarized, and the prognosis were followed up.Results:53 cases consisted of 34 boys and 19 girls with an age range of 0.2 to 14 years, the average age is 5.53±4.29.2 cases of HCM and 1 patient with LVNC had family history. The clinical manifestations were fatigue, shortness of breath, palpitation after activity, abdominal distension, double lower limbs and facial edema, decreased urine output, increased heart rate, and enlargement of the liver.4 cases manifested as paroxysmal syncope,6 cases had nocturnal paroxysmal dyspnea, orthopnea as onset of acute left heart failure.34 patients with DCM, LVNC and EFE most had systolic dysfunction,19 patients with HCM, RCM most had diastolic dysfunction. The heart rate increased, cardiac dullness boundary expansion ratio of 34 cases with cardiac systolic dysfunction of cardiomyopathy was higher than the patients with cardiac diastolic dysfunction of cardiomyopathy, and the difference was statistically significant (P< 0.05). The clinical cardiac function grade were moderate to severe in 34 patients with systolic dysfunction, the ratio was higher than the patients with cardiac diastolic dysfunction, and the difference was statistically significant (P< 0.05).29 cases of them were followed up for 6 months to 3 years, the ratio of symptoms disappeared or reduced and heart reduced was 58.62%.10 cases of 19 patients with diastolic dysfunction were followed up for 6 months to 3 years, the ratio of symptoms aggravated and death was 70%.Conclusion:In this study the onset age of children cardiomyopathy patients was small, more male than female, more for sporadic cases, with highest proportion of DCM, clinical findings of cardiac insufficiency was more commonly. The clinical feature was severe of patients with systolic dysfunction, but had relatively good prognosis. The clinical feature was mild of patients with diastolic dysfunction, but had poorer prognosis.Part II The clinical value of magnetic resonance imaging in diagnosis of children cardiomyopathy and evaluation of cardiac functionObjective:To evaluate the role of echocardiography (Echo) and cardiac magnetic resonance imaging (cMRI) in the diagnosis of children cardiomyopathy and the evaluation of cardiac function.Methods:53 patients with cardiomyopathy as the patients group,22 cases of healthy volunteers as the normal control group for the same period. Each research object of patients group and control group underwent both cMRI and Echo in the same day, and the cardiac functional grade of the patients were graded according to New York Heart Association (NYHA). Compared the advantages of two means in displaying the characteristic morphological changes of cardiomyopathy, and the difference between the two methods when measure the cardiac function indexes, including left ventricular end diastoiic volume (EDV), left ventricular end systolic volume (ESV), left ventricular ejection fraction (EF), left ventricular fractional shortening (FS), compared both of them with clinical cardiac function grade respectively. Compared the correlation between the clinical cardiac function grade and peak filling rate (PFR) measured by cMRI, the blood ratio in rapid filling period with atrial systolic mitral valve (E/A), isovolumic relaxation time (IVRT) by Echo.Results:cMRI could accurately display the characteristic morphological changes of cardiomyopathy, and late gadolinium enhancement on cMRI might suggest myocardial fibrosis, which had obvious advantages in the diagnosis of cardiomyopathy than Echo. The cardiac function indexes of EDV,ESV,EF,FS by cMRI were lower than Echo value both in the patient group and the control group, the difference was statistically significant (P<0.05). Index of the systolic function EF, FS of 2 measurement methods had correlation with clinical cardiac function grade(r=-0.577, r=-0.596, r=-0.583, r=-0.503); Index of the diastolic function PFR measured by cMRI had correlation with clinical cardiac function grade(r=-0.477), while Index of the diastolic function E/A> IVRT measured by Echo didn’t have correlation with clinical cardiac function grade(r=0.086, r=-0.057). There was statistical significance in cMRI cardiac function indexes in patient group with those in the control group (P<0.05). Index measured by cMRI of DCM, LVNC and EFE patients including EDV, ESV, EF, FS had significant difference with the normal control group (P<0.05), most had systolic dysfunction. Index measured by cMRI of HCM, RCM patients including PFR, EDV had significant difference with the normal control group (P<0.05), most had diastolic dysfunction.Conclusion:cMRI and Echo are of great value in the diagnosis and the assessment of cardiac function in children with cardiomyopathy, but the cMRI have more advantages of displaying cardiomyopathy characteristic morphological changes, is superior than Echo for the quantification of ventricular function in the abnormal left ventricle because it does not make invalid geometrical assumptions. cMRI has a better correlation with clinical cardiac function grade by NYHA and has a high clinical practical value.Part Ⅲ Mutations in cardiomyopathyObjective:To Screen the pathogenic genes in the patients, find out the characteristics of pathogenic genes of children cardiomyopathy, and compare with reported gene mutations of different ethnic groups.Methods:Gene Mutational analysis in a cohort of 35 patients with cardiomyopathy(22 boys and 13 girls) and 20 healthy volunteers, was performed by direct DNA sequencing of the genetic coding sequence with a total of 11 genes of encoding sarcomere protein gene (beta myosin heavy chain gene MYH7, myosin binding protein C MYBPC3, cardiac troponin T TNNT2, cardiac troponin I TNNI3,a-tropomyosin 1 TPM1, muscle ball light chain protein 2 MYL2, muscle protein light chain 3 MYL3, alpha actin ACTC1), Z disk protein gene (T cap protein TCAP), cell scaffold protein gene (tafazzin protein gene TAZ), nuclear membrane protein gene (nuclear fiber layer protein gene LMNA). First select 2 patients with DCM, 2 patients with HCM and 2 patients with RCM, a total of 6 cases of unrelated propositus by direct DNA sequencing. Test the positive results in the other 29 cases of the 35 cases samples and 20 cases samples of the control group.Results:In one case of HCM and one case of RCM, in MYH7 coding regions found a known missense mutation (A26V, rs 186964570 C> T), located in exon 4, the encoded amino acid from alanine (Ala) into valine (Val). In two cases of HCM, two cases of RCM and one case of DCM, in TNNT2 coding regions found a known synonymous mutation (11061, rs3729547 C> T), located in TNNT2 exon 10, the encoding amino acid remains the same, still for isoleucine (Ile). In one case of RCM found one known missense mutation (K260R, rs3730238 A> G), located in TNNT2 exon 14, the encoded amino acid from lysine (Lys) into arginine (Arg). The two known missense mutations might be benign in the reported function research. In two cases of HCM, two cases of RCM and two cases of DCM, in TPM1 and MYBPC3 coding regions were found unknown SNPs, which located in exon 4 and exon 19, did not cause the change of the amino acid sequence; In TNNI3 coding regions found an unknown SNP (K50Q, A> C), located in exon 4, the encoded amino acid from lysine (Lys) into glutamine (Gln); In ACTC1 coding regions found an unknown SNP (A206G, C> G), located in exon 5, the encoded amino acid from alanine (Ala) into a glycine (Gly). The two unknown missense mutations were found in the other 29 cases of the 35 cases samples and 20 cases samples of the control group, might be SNP loci.Conclusion:In this study we found a known synonymous mutation and 2 missense mutations located in MYH7 and TNNT2.Two unknown synonymous mutation,2 missense mutation SNPs located in TPMl, MYBPC3, TNNI3 and ACTC1. All in the gene encode sarcomere proteins, which was one of the reported main pathogenic gene of children cardiomyopathy. And the same gene mutations appeared in different clinical phenotypes, which prompted there existed a complex genetic modification.