Novel compound heterozygous mutations in the desmoplakin gene cause hair shaft abnormalities and culminate in lethal cardiomyopathy.

A 2-month-old white girl born to nonconsanguineous parents presented to the dermatology department with hair loss that had commenced a few months after birth. Although her hair loss later stabilized, it remained sparse. By the age of 2 years, she was noted to have developed focal keratoderma over pressure points of the soles. Aged 5 years, she was admitted to hospital with a chest infection, and investigations at that point revealed that she had a dilated cardiomyopathy. Subsequent genetic investigations identified compound heterozygous mutations in the 3' end of the desmoplakin (DSP) gene (7567delAAGA and 6577G>A), explaining the cardiocutaneous phenotype.

Hematopoietic progenitor cell deficiency in fetuses and children affected by Down's syndrome.

OBJECTIVES: There is an increased risk of myeloid malignancy in individuals with Down's syndrome (DS), which is associated with a mutation in exon 2 of the transcription factor GATA-1. It is recognized that there is accelerated telomere shortening in blood cells of children with DS similar to that in conditions such as Fanconi anemia and dyskeratosis congenita. The latter conditions are associated with stem cell deficiency and clonal change, including acute myeloid leukemia. In this study we address the questions 1) whether the accelerated telomere shortening is associated with progenitor/stem cell deficiency in individuals with DS, predisposing to clonal change and 2) whether the occurrence of reduced numbers of stem/progenitor cells precede the incidence of mutations in exon 2 of GATA-1. MATERIAL AND METHODS: Peripheral blood from fetuses (23-35 weeks gestation) and/or bone marrow from children affected by DS and age-matched hematologically healthy controls were analyzed for telomere length, content of stem/progenitor cells, and mutations in exon 2 of GATA-1. RESULTS: We found that hematopoietic stem/progenitor cell deficiency and telomere shortening occurs in individuals with DS in fetal life. Moreover, the presence of a low number of progenitor cells was not associated with mutations in exon 2 of GATA-1. CONCLUSIONS: We propose that stem cell deficiency may be a primary predisposing event to DS leukemia development.

Double-outlet right ventricle: morphologic demonstration using nuclear magnetic resonance imaging.

Sixteen patients with double-outlet right ventricle, aged 1 week to 29 years (median 5 months), were studied with a 1.5 tesla nuclear magnetic resonance (NMR) imaging scanner. Two-dimensional echocardiography was performed in all patients. Thirteen patients underwent angiography, including nine who underwent subsequent surgical correction. Three patients underwent postmortem examination. Small children and infants were scanned inside a 32 cm diameter proton head coil. Multiple 5 mm thick sections separated by 0.5 mm and gated to the patient's electrocardiogram were acquired with a spin-echo sequence and an echo time of 30 ms. A combination of standard and oblique imaging planes was used. Imaging times were less than 90 min. The NMR images were technically unsuitable in one patient because of excessive motion artifact. In the remaining patients, the diagnosis of double outlet right ventricle was confirmed and correlated with surgical and postmortem findings. The NMR images were particularly valuable in demonstrating the interrelations between the great arteries and the anatomy of the outlet septum and the spatial relations between the ventricular septal defect and the great arteries. Although the atrioventricular (AV) valves were not consistently demonstrated, NMR imaging in two patients identified abnormalities of the mitral valve that were not seen with two-dimensional echocardiography. In one patient who had a superoinferior arrangement of the ventricles, NMR imaging was the most useful imaging technique for demonstrating the anatomy. In patients with double-outlet right ventricle, NMR imaging can provide clinically relevant and accurate morphologic information that may contribute to future improvement in patient management.

Endocarditis with multiple intracardiac shunts: identification and repair.

An 8-year-old boy who suffered from Hirschsprung's disease had development of tricuspid valve endocarditis that progressed to aortic root abscess formation, development of a fistulous communication between aorta and right atrium, atrial and ventricular septal defects, and a left ventricle to right atrium defect. Several surgical procedures were required. Operation consisted initially of closure of the septal defects and aortic valve repair. This was followed by homograft replacement of the aortic valve for persistent infection, and further closure of a left ventricle to right atrium fistula.

Occlusion of Fontan fenestrations using the Amplatzer septal occluder.

OBJECTIVE: To evaluate the efficacy and safety of the Amplatzer septal occluder device for occlusion of Fontan fenestrations. SUBJECTS: Five children aged 5-10 years who had undergone a fenestrated Fontan operation. SETTING: Tertiary paediatric cardiology centre. METHODS: Each patient had right and left heart catheterisation to assess haemodynamic suitability for fenestration closure. Sizing of the defect was achieved with a balloon wedge catheter and transoesphageal echocardiography. Transcatheter occlusion of the fenestration was accomplished using a 4 mm device in three patients, and 5 mm or 9 mm devices in the other two patients. Residual shunting following occlusion was assessed using angiography and echocardiography. RESULTS: 100% occlusion rate of the fenestration was achieved in all patients. No complications or device failures were seen during the three month follow up period. CONCLUSION: The Amplatzer septal occluder device is safe, and effectively occludes the Fontan fenestration.

Complete heart block as a complication of varicella.

A case of varicella myocarditis complicated by permanent complete heart block requiring treatment with a permanent pacemaker is presented. Antiviral therapy with Acyclovir from the moment of presentation had no effect on the course of the heart block, but may have induced recovery of myocardial contractile dysfunction.

Distal ductal origin of the right pulmonary artery: prospective diagnosis and primary repair in infancy.

Absence of the proximal segment of the right pulmonary artery was diagnosed by echocardiography in two neonates. In both a right-sided duct communicated with the right pulmonary artery at the hilum of the lung. Successful surgical repair was undertaken at seven months and 10 weeks, respectively

Recurrence of aortic coarctation following repair by re-implantation of the subclavian artery.

Four patients mean age six months, range 11 days to 2 years, underwent repair of aortic coarctation by the technique of reimplantation of the subclavian artery (Mendonca repair). All developed re-coarctation within six months of an initially successful repair.

Magnetic resonance imaging of the great arteries in infants.

Sixty infants, aged 1-48 (median 8) weeks, with suspected congenital heart disease underwent a morphological evaluation of the great arteries using magnetic resonance imaging at 1.5 Tesla. Cross-sectional echocardiography was performed in all infants, angiography in 33 and surgery in 44. Multiple sections, 5 mm thick and gated to the patients' electrocardiogram were acquired in standard and oblique imaging planes. Ventriculo-arterial connexions were correctly identified in 54 infants (6 did not have intracardiac imaging performed) and an accurate description of the relationships of the great arteries was made in all. Magnetic resonance imaging clearly demonstrated normal and hypoplastic pulmonary arteries to the level of the first hilar branches and was better than echocardiography at confirming the presence or absence of central intrapericardial pulmonary arteries in 4 infants with pulmonary atresia. All parts of the thoracic aorta were accurately demonstrated and, in 23 infants with clinical suspicion of aortic coarctation, magnetic resonance images provided more information than echocardiography. Magnetic resonance imaging accurately demonstrates great arteries non-invasively supplementing echocardiographic and angiographic findings. In many cases, it replaces the need for invasive investigations.

Doppler evaluation of superior caval venous pathways after Mustard and Senning operations.

Doppler waveforms from the superior caval vein were analysed to evaluate the patency of superior caval venous pathways following venous redirection (Mustard and Senning) operations for complete transposition. The group consisted of 26 unselected survivors of Mustard (9 patients) and Senning operations (17 patients). Patients were examined a mean of 5.9 (range 0.1-15.3) years following operation and their age at study ranged from 0.4-25.3 years, mean 7.3 years. Doppler waveforms were correlated with digital subtraction angiograms, which were performed in every patient within 24 hours of the Doppler study. Totally occluded superior caval venous pathways were identified in 3 patients with digital subtraction angiography. The remaining patients had angiographically patent pathways. In the 23 patients with patent pathways, Doppler waveforms demonstrated an initial systolic peak smaller than a second diastolic peak. In the 3 patients with totally occluded pathways, the pattern of the waveform was reversed, with the systolic larger than the diastolic peak. Doppler examination of the superior caval vein is a quick and simple bedside method of accurately determining patency of superior caval venous pathways after atrial redirection procedures for complete transposition.

Spondylometaphyseal dysplasia Sedaghatian type associated with lethal arrhythmia and normal intrauterine growth in three siblings.

Spondylometaphyseal dysplasia of the Sedaghatian type is a rare dysplasia, characterized by mild limb shortening, but lethal in the neonatal period. We describe three affected male siblings, the offspring of consanguineous parents. One was stillborn. Neonatal death was due to cardiac arrhythmia in two of the siblings. This report confirms the importance of cardiac pathology in this probably autosomal recessive disorder. This diagnosis should be excluded in any newborn with an arrhythmia as the clinical limb shortening may not be obvious.

Anomalous right pulmonary artery origins in association with the fetal valproate syndrome.

Two cases are reported of fetal valproate syndrome in association with anomalous right pulmonary artery origin. Both diagnoses were confirmed following cardiac catheterisation as echocardiography alone was inadequate to define the anatomy. Anomalous right pulmonary artery origin is extremely rare making a chance association with fetal valproate syndrome very unlikely. We recommend that anomalous pulmonary artery origin is borne in mind in patients with valproate syndrome undergoing cardiac assessment, particularly as this may be a difficult diagnosis to make on echocardiography.

Infective endocarditis in newborn infants with structurally normal hearts.

Twelve infants with structurally normal hearts were demonstrated to have intracardiac vegetations on echocardiography and diagnosed as having infective endocarditis. All were found in the right side of the heart, most frequently at the junction of the superior vena cava and the right atrium and in no case involved the tricuspid or pulmonary valves. Most were diagnosed in the course of investigation of repeatedly positive blood cultures, despite appropriate antibiotic therapy. Coagulase-negative staphylococci were isolated from blood culture in nine infants, and Streptococcus sanguis and Candida albicans from one each. All infants had had intracardiac central lines inserted to facilitate venous access, either by a percutaneous technique or as a formal surgical procedure. Eight (67%) were successfully treated and made a full recovery. Cardiac murmurs were absent in all of the cases. Echocardiography should be included in the investigation of all neonates with persistently positive blood culture, particularly when intracardiac lines have been sited. Right-sided, non-valvar lesions and infection with coagulase-negative staphylococci may carry a better prognosis than previously reported.

Growth of the pulmonary artery after neonatal balloon dilatation of the right ventricular outflow tract in an infant with the tetralogy of Fallot and atrioventricular septal defect.

A two week old girl with tetralogy of Fallot and atrioventricular septal defect underwent palliation, for severe hypoxaemia, by balloon dilatation to the right ventricular outflow tract. This procedure was repeated once over the next eight months without complications. Serial right ventricular angiograms showed growth of the hypoplastic pulmonary ring ("annulus"), trunk, and arteries. Balloon dilatation is an alternative palliative procedure for patients with the tetralogy of Fallot which may promote growth of the pulmonary ring, trunk, and arteries.

Balloon dilatation of a stenosed modified (polytetrafluoroethylene) Blalock-Taussig shunt.

A 17 month old girl with tricuspid atresia, ventricular septal defect, subvalvar and valvar pulmonary stenosis, and increasing cyanosis had angiographic evidence of proximal stenosis of a right modified (5 mm diameter) Blalock-Taussig shunt. She underwent palliative balloon angioplasty with a 6 mm Schneider balloon catheter. Successful dilatation was achieved without complication. Four months later there was subjective clinical improvement with a rise in systemic arterial saturation. Repeat angiography showed patency of the shunt without restenosis or formation of an aneurysm.

Lacunar infarcts in polycythaemia with raised packed cell volumes.

Lacunar (small deep cerebral infarcts) infarction is described in association with raised packed cell volumes. Two patients had polycythaemia vera, one stress polycythaemia. They presented with transient ischaemic episodes and were shown by computed tomography to have lacunes deep in the basal ganglia and internal capsule. Such lesions may be caused by small vessel occlusions related to increased viscosity and impaired oxygen consumption by adjacent tissues. Finding a raised packed cell volume in patients with lacunes and transient ischaemic attacks offers a further possibility of treatment.

Dilatation with progressively larger balloons for severe stenosis of the pulmonary valve presenting in the late neonatal period and early infancy.

Balloon dilatation in infants with severe pulmonary valve stenosis may not be a straightforward procedure once the arterial duct has closed. Balloon dilatation was attempted in three neonates and infants. In an 11 week old infant hypotension and bradycardia developed shortly after a 5 French end hole catheter was passed through the severely stenosed pulmonary valve. An emergency Waterston shunt was subsequently performed, but he died three days later. After this experience the technique was modified so that progressively larger balloons were used for dilatation in two infants, aged one and three weeks, with severe pulmonary valve stenosis in whom the arterial duct had closed. It was successful in both.

Severe haemolysis after percutaneous closure of a ductus arteriosus (arterial duct).

Severe mechanical haemolysis occurred after transcatheter occlusion of a ductus arteriosus (arterial duct) by a Rashkind double umbrella prosthesis. Surgical removal of the device and ligation of the duct were required before haemolysis was abolished.

Complications of the naevoid basal cell carcinoma syndrome: results of a population based study.

There are many potential complications which have been reported in association with the naevoid basal cell carcinoma syndrome. We have been able to show the relative frequencies of these problems in a population based study of 84 cases in the north west of England. The major complications of basal cell carcinomas and jaw cysts occur in over 90% of patients by 40 years of age, but may both occur before 10 years of age. Less well described complications are ovarian calcification or fibroma (24%), medulloblastoma (5%), cardiac fibroma (3%), cleft palate (5%), and ophthalmic abnormalities such as squint or cataract (26%). This study more clearly defines the possible complications of the syndrome and gives clearer guidelines for counselling and screening affected and at risk persons.