Fluorinated steroids do not improve outcome of isolated atrioventricular block.

INTRODUCTION: Congenital atrioventricular block (CAVB) is a rare disorder with a significant morbidity and mortality. Consensus regarding the prescription and efficacy of prenatal corticosteroids is lacking. This nationwide study was initiated to evaluate the effects of prenatal treatment with corticosteroids on the outcome of CAVB in The Netherlands. METHODS: All fetuses identified with isolated congenital AVB-II° or AVB-III° in any of the eight academic fetal heart centers of The Netherlands between 2003 and 2013 were included and reviewed. RESULTS: Fifty-six fetuses were included. Fourteen (25%) fetuses were treated with dexamethasone. We found no differences between the steroid-treated and untreated cases regarding in utero progression of the AVB (63% vs 67% respectively), survival to birth (86% vs 84%), pacemaker implantations (74% vs 58%) or long-term dilated cardiomyopathy (13% vs 17%). Steroid treated fetuses demonstrated more in utero growth restriction (38% vs 11%). CONCLUSION: No benefit from prenatal corticosteroid treatment was demonstrated for fetuses with isolated CAVB in this study. However, we found negative side effects. Our data provide no evidence to support the routine administration of corticosteroids for the treatment of fetal CAVB.

Prenatal ultrasound diagnosis of MYH7 non-compaction cardiomyopathy.

We report on two prenatal ultrasound diagnoses of left ventricular non-compaction cardiomyopathy (LVNC) associated with mutation of the cardiac ß-myosin heavy chain gene (MYH7). LVNC is characterized by a trabecular meshwork and deep intertrabecular myocardial recesses communicating with the left ventricular cavity. Clinical features range from non-penetrant disease in adult carriers to heart failure, arrhythmia and thromboembolism. Both cases showed cardiomegaly on prenatal ultrasound examinations, with features indicating non-compaction of the myocardium apparent in the third trimester. Mutations in the MYH7 gene were identified postnatally in each case in both the proband and the father. One infant underwent surgical mitral valvuloplasty and a mechanical valve implant later; in the other, left ventricular function was unimpaired at birth. Cardiac function in both cases remained stable at last follow-up. These cases highlight the importance of prenatal ultrasound diagnosis of LVNC and the need for cardiologic and molecular testing of first-degree relatives who may be unknown carriers of an MYH7 mutation.

Effect of enzyme therapy in juvenile patients with Pompe disease: a three-year open-label study.

Pompe disease is a rare neuromuscular disorder caused by deficiency of acid α-glucosidase. Treatment with recombinant human α-glucosidase recently received marketing approval based on prolonged survival of affected infants. The current open-label study was performed to evaluate the response in older children (age 5.9-15.2 years). The five patients that we studied had limb-girdle muscle weakness and three of them also had decreased pulmonary function in upright and supine position. They received 20-mg/kg recombinant human α-glucosidase every two weeks over a 3-year period. No infusion-associated reactions were observed. Pulmonary function remained stable (n = 4) or improved slightly (n = 1). Muscle strength increased. Only one patient approached the normal range. Patients obtained higher scores on the Quick Motor Function Test. None of the patients deteriorated. Follow-up data of two unmatched historical cohorts of adults and children with Pompe disease were used for comparison. They showed an average decline in pulmonary function of 1.6% and 5% per year. Data on muscle strength and function of untreated children were not available. Further studies are required.

Cardiac evaluation in children and adults with Pompe disease sharing the common c.-32-13T>G genotype rarely reveals abnormalities.

BACKGROUND AND OBJECTIVE: Pompe disease is an inherited metabolic disorder caused by deficiency of acid alpha-glucosidase. All affected neonates have a severe hypertrophic cardiomyopathy, leading to cardiac failure and death within the first year of life. We investigated the presence and extent of cardiac involvement in children and adults with Pompe disease with the common c.-32-13T>G genotype to determine the usefulness of cardiac screening in these patients with relatively 'milder' phenotypes. METHODS: Cardiac dimensions and function were evaluated through echocardiography, electrocardiography and Holter monitoring. The total group comprised 68 patients with Pompe disease, of whom 22 patients had disease onset before the age of 18. RESULTS: Two patients (3%) had cardiac abnormalities possibly related to Pompe disease: Electrocardiography showed a Wolff-Parkinson-White pattern in an 8-year-old girl, and one severely affected adult patient had a mild hypertrophic cardiomyopathy. This hypertrophy did not change during treatment with recombinant human alpha-glucosidase. In addition, four adult patients showed minor cardiac abnormalities which did not exceed the prevalence in the general population and were attributed to advanced age, hypertension or pre-existing cardiac pathology unrelated to Pompe disease. CONCLUSIONS: Cardiac involvement is rare in Pompe patients with the common c.-32-13T>G genotype. The younger patients were not more frequently affected than the adults. Electrocardiographic evaluation appears to be appropriate as initial screening tool. Extensive cardiac screening seems indicated only if the electrocardiogram is abnormal or the patient has a history of cardiac disease.

Poor outcome in Down syndrome fetuses with cardiac anomalies or growth retardation.

The outcome of Down syndrome fetuses presenting with sonographic abnormalities in the second or third trimester is unclear. Therefore, we studied 55 pregnancies referred because of sonographically suspected fetal structural anomalies or growth retardation due to trisomy 21. A detailed ultrasound scan was performed in all cases to delineate the structural anomalies. Congenital heart malformations (CHMs) were diagnosed pre- and postnatally in 29 out of 55 Down fetuses (53%), with complete or incomplete atrioventricular septal defects (AVSDs) and ventricular septal defects (VSDs) being the most frequent anomalies. The most frequent noncardiac findings were a short femur (45%) and a small-for-gestational age (SGA) fetus (27%). Termination of pregnancy was carried out in 25 out of 55 pregnancies (45%). Of the 30 continued pregnancies, 10 ended with intrauterine death. The remaining 20 pregnancies resulted in the delivery of a live-born infant whose prognosis was poor, with a 1-year survival of only 60%. Combining intrauterine death and death in the first year indicated that the overall survival rate was only 40%. Fatal outcome was noted in 68% (13/19) in the presence of CHM, in 83% (10/12) in SGA fetuses, in 86% (6/7) in combined CHM and SGA, but only in 17% (1/6) in the absence of CHM and SGA. This study indictes that second- and third-trimester in utero diagnosis of Down syndrome has a poor outcome when associated with CHM and/or SGA. This is important in the genetic counseling of the parents.