Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations. (9/3692)

To better understand the role of TBX5, a T-box containing transcription factor in forelimb and heart development, we have studied the clinical features of Holt-Oram syndrome caused by 10 different TBX5 mutations. Defects predicted to create null alleles caused substantial abnormalities both in limb and heart. In contrast, missense mutations produced distinct phenotypes: Gly80Arg caused significant cardiac malformations but only minor skeletal abnormalities; and Arg237Gln and Arg237Trp caused extensive upper limb malformations but less significant cardiac abnormalities. Amino acids altered by missense mutations were located on the three-dimensional structure of a related T-box transcription factor, Xbra, bound to DNA. Residue 80 is highly conserved within T-box sequences that interact with the major groove of target DNA; residue 237 is located in the T-box domain that selectively binds to the minor groove of DNA. These structural data, taken together with the predominant cardiac or skeletal phenotype produced by each missense mutation, suggest that organ-specific gene activation by TBX5 is predicated on biophysical interactions with different target DNA sequences.  (+info)

Comparison of prenatal ultrasound and postmortem findings in fetuses and infants with congenital heart defects. (10/3692)

OBJECTIVE: Detection of congenital heart defects by prenatal ultrasound examination has been one of the great challenges since the investigation for fetal anomalies became part of the routine fetal examination. This prospective study was designed to evaluate the concordance of prenatal ultrasound findings with autopsy examination in a population consisting of both referred women and non-selected pregnant women. DESIGN: Criteria for inclusion were an ultrasound examination at the National Center for Fetal Medicine and an autopsy performed during the years 1985-94. Results from the ultrasound and autopsy examinations were systematized into categories depending on the degree of concordance. RESULTS: Of 408 infants and fetuses with developmental anomalies, 106 (26%) had congenital heart defects. In 63 (59%) of these 106 cases, the heart defect was the principal reason for the termination of pregnancy or the cause of death. Excluding five cases with a secundum atrial septal defect, there was complete agreement between the ultrasound examination and the autopsy findings in 74 (73%) of 101 cases. In 18 cases, there were minor discrepancies between ultrasound and autopsy findings. The main diagnosis was thus correct in 92 cases (91%). From the first time period (1985-89) to the second (1990-94), the detection rate of all heart defects increased from 48% to 82%. CONCLUSION: This study confirms a good correlation between ultrasound and autopsy diagnoses in fetuses and infants with congenital heart defects. A significant improvement in the detection of heart defects occurred from the first time period to the second and was probably due to increased experience and technical advances.  (+info)

Abnormal renal functions in cyanotic congential heart disease. (11/3692)

Children with cyanotic congenital heart disease had a decreased glomerular filtration rate (71-8 +/- 18-9 ml/min per 1-73 m2) measured by endogenous creatinine clearances, compared with children who had had complete corrective surgery, children with noncyanotic heart disease, and normal children. There was a significant correlation between low glomerular filtration rate and haematocrit values above 50%. Daily urinary sodium excretion was reduced in the cyanotic patients.  (+info)

Double outlet right ventricle. Study of 27 cases. (12/3692)

Out of 1610 children's hearts with congenital malformations there were 27 specimens showing double outlet right ventricle. Cases with dextrocardia, situs inversus, or l-venticular loop were excluded. Anatomical examination was performed with particular reference to the infundibular region, the great vessels, and the ventricular septum. The commonest associated malformations were ventricular septal defect and pulmonary stenosis. Aortic stenosis was the predominant finding in those cases dying in the neonatal period. An aortic conus was associated with pulmonary stenosis, ventricular septal defect, and d-transposition, a pulmonary conus with ventricular septal defect and a double conus with stenosis of either great vessel. The anterior vessel always had a muscular conus and the posterior vessel was commonly stenotic.  (+info)

Delineation of the critical deletion region for congenital heart defects, on chromosome 8p23.1. (13/3692)

Deletions in the distal region of chromosome 8p (del8p) are associated with congenital heart malformations. Other major manifestations include microcephaly, intrauterine growth retardation, mental retardation, and a characteristic hyperactive, impulsive behavior. We studied genotype-phenotype correlations in nine unrelated patients with a de novo del8p, by using the combination of classic cytogenetics, FISH, and the analysis of polymorphic DNA markers. With the exception of one large terminal deletion, all deletions were interstitial. In five patients, a commonly deleted region of approximately 6 Mb was present, with breakpoints clustering in the same regions. One patient without a heart defect or microcephaly but with mild mental retardation and characteristic behavior had a smaller deletion within this commonly deleted region. Two patients without a heart defect had a more proximal interstitial deletion that did not overlap with the commonly deleted region. Taken together, these data allowed us to define the critical deletion regions for the major features of a del8p.  (+info)

Modified Fontan operation. Considerations for the determination of the appropriate procedure. (14/3692)

BACKGROUND: Although the surgical results of the modified Fontan operation continues to improve, there are various advantages and disadvantages in terms of the post operative condition associated with the Fontan modifications. Late morbidity and mortality are mainly due to arrhythmias, thromboembolic complications, systemic venous hypertension and infective endocarditis. We reported our experience of the modified Fontan operation to determine an appropriate procedure for each patient. METHODS AND RESULTS: Seven patients (ranging from the age 1-14 years) underwent a modified Fontan operation including a lateral tunnel (n = 1), extracardiac conduit (n = 2) and autogenous atrial tunnel (n = 4). There was one hospital death due to sepsis in which the patient underwent lateral tunnel procedure. The mean follow up of another six patients was 20 months (ranging from 1-39 months) and all patients were classified as NYHA class I, and remained in normal sinus rhythm without any thromboembolic complications. CONCLUSIONS: When using the autogenous atrial tunnel, there are potential advantages; it is not associated with thromboembolism or endocarditis and has growth potential. However, in high-risk patients with increased pulmonary vascular resistance, impaired ventricular function and pre-operative atrial arrhythmias, it appears reasonable to use an extracardiac conduit.  (+info)

Molecular genetic analysis of the DiGeorge syndrome among Korean patients with congenital heart disease. (15/3692)

The DiGeorge syndrome (DGS) is a developmental defect of the third and fourth pharyngeal pouches, which is associated with congenital heart defects, hypoparathyroidism, cell-mediated immunodeficiency, velo-pharyngeal insufficiency and craniofacial dysmorphism. The aetiological factor in a great majority of DGS cases is monosomy for the chromosomal region 22q11. To analyze DGS at the molecular level, a new molecular probe (DGCR680) encompassing the ADU balanced translocation breakpoint was prepared. When 13 Korean patients with DGS-type congenital heart disease were analyzed with this probe, 9 turned out to have a deletion at this locus, and all of them except one exhibited a typical facial dysmorphism associated DGS. Though only 9 independent patients were detected to have a deletion at the locus using the commercial probe N25 (D22S75), which maps at about 160 kb from the ADU breakpoint to the telomeric end, results from fluorescence in situ hybridization revealed a deletion in all cases tested at this locus. Two patients who had a deletion at the locus D22S75 but not at DGCR680 did not exhibit any DGS-type facial abnormalities. This result implies that the 680 bp probe covering the ADU translocation breakpoint might be a candidate for a molecular marker that can distinguish a specific phenotype, such as facial features associated with the DiGeorge syndrome. This study also suggested that systematic approaches with several small DNA probes along the DGCR could help to dissect the complex phenotypes associated with the DiGeorge syndrome, such as cardiac defects, abnormal faces, thymic hypoplasia, cleft palate, and hypocalcemia, etc.  (+info)

Quantitative morphological studies of developing human cerebellar cortex in various disease states. (16/3692)

A quantitative morphological assessment was carried out of the cellularity and staining properties of the cells of the layers of the human cerebellar cortex, both in the normal child and in 41 children suffering from a series of disorders including mental retardation. A computerized image analyser and highly standardized procedures were used. All of the cases of mental retardation and some cases with congenital cardiac anomalies showed abnormal cell concentrations and staining properties. 3 cases of 'cot death' also showed abnormal results. These findings are presented as a new measurable aspect of brain disease, and as a indication for further study.  (+info)