Infective endocarditis in patients after percutaneous pulmonary valve implantation with the stent-mounted bovine jugular vein valve: Clinical experience and evaluation of the modified Duke criteria.

AIMS: Percutaneous pulmonary valve implantation (PPVI) has proven good hemodynamic results. As infective endocarditis (IE) remains a potential complication with limited available clinical data, we reviewed our patient records to improve future strategies of IE prevention, diagnosis and treatment. METHODS: Medical records of all patients diagnosed with Melody® valve IE according to the modified Duke criteria were retrospectively analyzed in three Belgian tertiary centers. RESULTS: 23 IE episodes in 22 out of 240 patients were identified (incidence 2.4% / patient year) with a clear male predominance (86%). Median age at IE was 17.9 years (range 8.2-45.9 years) and median time from PPVI to IE was 2.4 years (range 0.7-8 years). Streptococcal species caused 10 infections (43%), followed by Staphylococcus aureus (n = 5, 22%). In 13/23 IE episodes a possible entry-point was identified (57%). IE was classified as definite in 15 (65%) and as possible in 8 (35%) cases due to limitations of imaging. Echocardiography visualized vegetations in only 10 patients. PET-CT showed positive FDG signals in 5/7 patients (71%) and intracardiac echocardiography a vegetation in 1/1 patient (100%). Eleven cases (48%) had a hemodynamically relevant pulmonary stenosis at IE presentation. Nine early and 6 late percutaneous or surgical re-interventions were performed. No IE related deaths occurred. CONCLUSIONS: IE after Melody® valve PPVI is associated with a relevant need of re-interventions. Communication to patients and physicians about risk factors is essential in prevention. The modified Duke criteria underperformed in diagnosing definite IE, but inclusion of new imaging modalities might improve diagnostic performance.

20 years of arterial switch operation for simple TGA.

BACKGROUND: Arterial switch operation became the golden treatment for simple transposition of the great arteries (sTGA). We describe our experience with the arterial switch operation regarding long-term outcome and the need for re-intervention. Nevertheless, supravalvular pulmonary stenosis (SPS) remains a concern in the long run. We assess the evolution of SPS over time and evaluate the effect of technical modifications on SPS during our experience. METHODS: We performed a retrospective study on 133 patients operated with ASO for TGA between October 1991 and November 2009. Last report method was used. We reviewed our pediatric cardiology and cardiac surgery database to examine the echocardiographic data and electrocardiograms. A mean follow-up of 9.2 years (+/- 5.83 SD) was reached. RESULTS: One (0.8%) patient deceased postoperatively due to cardiogenic shock. The overall actuarial freedom from reoperation (open and percutaneous) was 88.1%, 78.5% and 76.9% at 1, 5 and 10 years. SPS needed to be treated in 17 patients. Valve regurgitation at final investigation was maximal moderate in 5 patients for the aortic valve, 10 for pulmonary valve and 3 in tricuspid valve. CONCLUSIONS: ASO shows excellent long-term results in sTGA with a very low morbidity and mortality and is therefore the procedure of choice. Re-intervention rate is determined by SPS. Since the extensive mobilization of the pulmonary arteries and the creation of a longer neo-pulmonary root, reduction in SPS was seen with no re-interventions in the second half of the group. To obtain a final comparison with the atrial switch operation, a longer Follow-up is necessary.

Transapical left ventricular access for difficult to reach interventional targets in the left heart.

OBJECTIVE: Interventional targets may be virtually "excluded" due to vascular access problems or complex previous surgical procedures. This study reviews our experience using transapical ventricular puncture to gain direct access to the systemic ventricle. PATIENTS: Patient 1 (74 years, 2 previous sternotomies), patient 2 (66 years, 5 previous sternotomies), and patient 5 (69 years, 3 previous sternotomies) with prosthetic valves had paravalvular mitral valve leaks. Patient 3 (6.3 years, 2 previous sternotomies) with an extracardiac Fontan conduit, had a significant residual leak after two previous surgical attempts of patch closure of a severely regurgitant right atrioventricular valve. Patient 4 (10 months) had failure of standard ablation of the posteroseptal region of the mitral valve with persistent life-threatening episodes of ventricular tachycardia. METHODS: Procedures were performed under general anesthesia. Entry site was percutaneous in three patients and in two (and one conversion) a mini-thoracotomy was used. Sheaths were placed (6 F) using standard Seldinger technique, followed by the procedure as required. Direct surgical closure of the puncture site was done in 4 patients and in patient 3, a percutaneous vascular occlusion device was used. RESULTS: Easy and immediate access was obtained in all patients. The paravalvular leaks were crossed within seconds and completely closed with Amplatzer occluders. In patient 3 the valve was crossed using a Brokenbrough needle and a 12-mm Amplatzer device was placed in the patch leak. Patient 4 was successfully ablated using a 7-F irrigated catheter endo- and epicardially. Complications were in the percutaneous puncture group: in one patient a coronary artery was punctured and in one a hemothorax developed. CONCLUSION: Direct left ventricular puncture offers a very useful alternative access site in selected patients to reach "inaccessible" targets for certain percutaneous interventions in patients where standard approaches may be impossible or difficult.

Stenting of hypoplastic aortic segments with mild pressure gradients and arterial hypertension.

OBJECTIVE: To determine the safety, feasibility and effectiveness of stent expansion of hypoplastic aortic segments with pressure gradients in patients with arterial hypertension. DESIGN: Non-randomised prospective clinical trial. SETTING: Tertiary referral centre, congenital cardiac unit. PATIENT SELECTION: 20 consecutive patients (median age 14.5 years, range 11.6-38.8 years) with arterial hypertension and a hypoplastic segment of the aorta. Seventeen patients had successful previous arch interventions in a coarctation site. INTERVENTIONS: Stent deployment in hypoplastic arch segments. MAIN OUTCOME MEASURES: Gradient across the aortic arch; complications early and during follow up; residual hypertension. RESULTS: 23 stents were deployed: 13 in the cross and 10 in the isthmus. The mean gradient across the aortic arch decreased from 16 (SD 6) (median 17) to 3 (4) (median 1) mm Hg (p < 0.001). In a few patients a mild gradient persisted just distal to the left carotid artery due to residual orificial narrowing or acute angulation. No complications occurred during or after the procedure. During follow up of 2.2 years (range 0.2-4.8 years) arterial hypertension resolved in 10 patients and 10 required residual drug treatment with better control of blood pressures. CONCLUSIONS: Pressure loss due to residual hypoplastic aortic segments can be treated effectively and safely with stent expansion. Some patients remain mildly hypertensive and require additional drug treatment.

Idebenone treatment in Friedreich's ataxia: neurological, cardiac, and biochemical monitoring.

The authors report 1-year prospective data on eight patients with Friedreich ataxia. Idebenone did not halt the progression of ataxia. At the end of therapy, cardiac ultrasound demonstrated significant reduction of cardiac hypertrophy in six of eight patients. Cardiac strain and strain rate imaging showed that the reduction of hypertrophy is preceded by an early and linear improvement in cardiac function. Idebenone reduced erythrocyte protoporphyrin IX levels in five of six patients with elevated baseline levels; however, changes did not consistently relate to cardiac improvement.

New ultrasound methods to quantify regional myocardial function in children with heart disease.

From a temporally resolved radio-frequency data set, a series of new developing indices of regional myocardial deformation can be measured. These may be important new data sets to quantify regional radial and long axis function of the left or right ventricle in children with acquired or congenital heart disease. Using color Doppler methodology unidimensional regional myocardial strain rates (SR) and natural strain (e) can now be calculated from local myocardial velocity data sets. Normal regional velocity, SR, and e values have already been determined in older children and should form the database for studies into acquired or congenital heart disease in this age group. Neonatal and infant values have yet to be determined. This article will present preliminary data on the potential clinical value of ultrasonic regional SR and e imaging in children and will discuss the close interrelation of these new regional function parameters with an alternative approach to quantification: the measurement of local cyclical changes in integrated backscatter levels.

Recurrent involvement of chromosomal region 6q21 in heterotaxy.

We present a patient with heterotaxy and a de novo, apparently balanced reciprocal translocation with breakpoints at 6q21 and 20p13. Another patient with heterotaxy was previously reported with a de novo balanced translocation involving chromosome band 6q21. The breakpoints in both patients on 6q21 were found to be located in the same chromosomal region spanning maximally 2 Mb. We speculate that the two breakpoints lead to the disruption of the function of a single gene, either directly or through long distance effects. Alternatively, the present observation suggests additional heterogeneity in heterotaxy in humans.

Cardiorespiratory exercise function after the arterial switch operation for transposition of the great arteries.

AIMS: This study compares the functional outcome and cardiorespiratory response to exercise, in patients who have undergone arterial switch for transposition of the great arteries, with normal controls and patients who have undergone atrial switch operation. METHODS AND RESULTS: Fifteen patients who had undergone arterial switch (mean age 8.5+/-2.9 years) were compared to 32 patients who had undergone atrial switch (9.2+/-1.8 years) and 27 normal controls (8.5+/-2.1 years). Exercise testing was performed on a treadmill and gas exchange measured breath-by-breath. Aerobic capacity, assessed by determination of the ventilatory anaerobic threshold, averaged 91+/-7.8% of normal (95% confidence limits: 92-108%) for arterial switch and 75.1+/-13.1% for atrial switch (P<0.001 patients vs normals). Aerobic exercise function was evaluated by calculation of the slope of oxygen uptake vs exercise intensity. The mean value for this slope was 2.0+/-0.25 for arterial switch, 2.5+/-0.46 for normals and 1.7+/-0.80 for atrial switch (P<0.05; patients vs normals). Efficiency of the pulmonary gas exchange was assessed by calculation of the slope of ventilation vs carbon dioxide output during exercise. This averaged 38.7+/-14.7 for arterial switch, 48.1+/-14.1 for atrial switch and 30.3+/-7.6 for normals (P<0.001; patients vs normals). CONCLUSION: Cardiorespiratory exercise function is at, or slightly below, the lower limit of normal in patients with arterial switch, while the lowest values were observed for those who had undergone atrial switch.

Long-term assessment and serial evaluation of cardiorespiratory exercise performance and cardiac function in patients with atrial switch operation for complete transposition.

BACKGROUND: At present, a considerable number of patients survive who underwent an atrial switch operation for correction of complete transposition. Our study aimed to assess their long-term exercise performance and the serial evolution of cardiac function. METHODS: We studied 22 patients 5 to 17 years after an atrial switch operation, and followed them serially for 3.5 +/- 2 years after the first evaluation. Cardiorespiratory exercise function was assessed by analysis of gas exhange and by determination of the ventilatory anaerobic threshold. Echocardiography was performed on all evaluations. RESULTS: All patients were in Class I of the classification of the New York Heart Association at all assessments. Ventilatory anaerobic threshold, however, was significantly lower than normal. It averaged 77.9% +/- 13.7 of the normal mean value at the initial evaluation, and remained stable when re-evaluated later (76.2 +/- 13.7%). At the initial study, the increase in oxygen uptake during graded exercise was below the 95% confidence limit in 6 of the patients, and was below this level in 10 patients at re-assessment. The subnormal values for oxygen uptake during submaximal exercise were associated with moderate to severe haemodynamic dysfunction. At echocardiography, 15 of 17 patients studied twice had mild to moderate right ventricular dilation and tricuspidregurgiation, which remained virtually the same at reasssesment. A stable sinus rhythm was initially present in 17 patients, and persisted in 15 patients during follow-up. CONCLUSION: At medium term follow-up, cardiorespiratory exercise performance remains stable in patients after atrial switch repair. Serial exercise testing appears useful, because in individual patients in the present study, a decreasing exercise tolerance correlated with development of haemodynamic sequels.

Homograft insertion for pulmonary regurgitation after repair of tetralogy of fallot improves cardiorespiratory exercise performance.

Surgical repair of tetralogy of Fallot (TOF) with reconstruction of the right ventricular (RV) outflow tract invariably results in pulmonary regurgitation. Chronic pulmonary regurgitation has been associated with RV dysfunction and decreased exercise performance. The present study assessed the influence of pulmonary valve replacement (PVR) for severe pulmonary regurgitation after previous TOF repair on cardiorespiratory exercise performance and RV function. Eighteen patients, between the ages of 8 and 18 years, underwent an exercise test and a cardiac magnetic resonance imaging scan at least 1 year after PVR. The exercise data were compared with those obtained from 24 age-matched normal controls and 27 age-matched patients with repaired TOF and a moderate degree of pulmonary regurgitation. A subgroup of 11 patients had an exercise test performed before and after PVR. Cardiopulmonary exercise performance was evaluated by determination of the ventilatory anaerobic threshold (VAT) and by the steepness of the slope of oxygen uptake versus exercise intensity (SVO2). After PVR there was a significant increase in VAT (86+/-11% before to 106.9+/-14% after, p = 0.03) and in SVO2 (1.71+/-0.47 to 2.3+/-0.39, p = 0.004). In patients examined after PVR, the VAT and SVO2 values were not significantly different from the values in the normal controls (104+/-15% [p>0.05] and 2.03+/-0.77 after PVR vs. 2.42+/-0.68 [p>0.25], respectively). In contrast, patients with repaired TOF and a moderate degree of pulmonary regurgitation had a significantly lower VAT (86+/-11%, p<0.05) and SVO2 (1.8+/-0.74 vs. 2.42+/-0.68, p<0.05) than normal controls. Magnetic resonance imaging studies revealed residual RV dilatation and dysfunction. However, there was no correlation between RV dilatation and RV dysfunction and aerobic exercise capacity. It is concluded that aerobic exercise capacity substantially improves after PVR for severe pulmonary regurgitation after previous TOF repair. Although the right ventricle remains significantly dilated and hypocontractile, there is no relation between RV function and exercise performance.

Isolated supravalvular aortic stenosis: functional haploinsufficiency of the elastin gene as a result of nonsense-mediated decay.

We have used single-strand conformation and heteroduplex analyses of genomic amplimers to identify point mutations within the elastin gene (ELN) in patients with non-syndromic supravalvular aortic stenosis (SVAS) from a total of eight unrelated families. Six novel point mutations were identified. We have collected detailed clinical information on mutation carriers and demonstrated significant non-penetrance in some of the families. Together with the new mutations described here, 14 point mutations have been reported in SVAS patients, and 10 of these result in premature stop codons (PTCs). We have analyzed the expression of ELN alleles in skin fibroblasts from one SVAS patient and shown that PTC mutations indeed result in selective elimination of mutant transcripts. Inhibition of the nonsense-mediated decay mechanism by cycloheximide resulted in the stabilization of mutant elastin mRNA. Allelic inactivation by the ELN mutation in this patient led to an overall decrease of the steady state levels of elastin mRNA. Finally, we have demonstrated reduced synthesis and secretion of tropoelastin by skin fibroblasts from the same SVAS patient. We conclude that PTC mutations in ELN result in nonsense-mediated decay of mutant mRNA in this patient. Given the predominance of PTC mutations in SVAS, we suggest that functional haploinsufficiency may be a pathomechanism underlying most cases of non-syndromic SVAS.

Oxygen uptake versus exercise intensity: a new concept in assessing cardiovascular exercise function in patients with congenital heart disease.

OBJECTIVE: To assess the relation between exercise intensity and oxygen uptake during graded exercise in paediatric patients who underwent surgical repair of congenital heart disease, and to compare it with conventional measures of aerobic exercise function. DESIGN: Cross sectional study. Exercise testing was performed on a treadmill and gas exchange was measured on a breath by breath basis. PATIENTS: 29 patients who underwent an atrial switch operation for transposition of the great arteries (TGA) (mean (SD) age at testing 10.3 (2.5) years) and 30 patients who underwent total repair of tetralogy of Fallot (TF) (age 12.1 (3.3) years) performed graded exercise testing. Exercise responses were compared with data obtained in 24 normal controls (age 11.4 (2.6) years). RESULTS: The slope of oxygen uptake versus exercise intensity averaged 1.50 (0. 64) ml O(2)/min(2)/kg in the patients with TGA and 1.68 (0.75) ml O(2)/min(2)/kg after TF repair, both lower (p < 0.005) than in normal controls (2.42 (0.68) ml O(2)/min(2)/kg). The lower slope of oxygen uptake was correlated with a subnormal value for ventilatory anaerobic threshold, which averaged 78.0 (13.3)% of normal in TGA and 85.1 (10.6)% in TF. This was associated with a steeper slope (p = 0.001) of carbon dioxide output versus oxygen uptake above the ventilatory anaerobic threshold in TGA (1.26 (0.20)) and TF (1.20 (0. 18)) compared with the normal controls (1.05 (0.13)), and also a steeper slope of ventilation versus carbon dioxide in TGA (47.0 (15. 4)) and TF (41.5 (13.7)) than in the controls (30.3 (8.5)). CONCLUSIONS: Calculation of the steepness of the slope of oxygen uptake versus exercise intensity is a valid measurement of oxygen flow to the exercising tissues, which may be limited in congenital heart disease.

Neonatal pulmonary artery banding does not compromise the short-term function of a Damus-Kaye-Stansel connection.

BACKGROUND: The surgical approach of neonates with a functionally univentricular heart, transposition of the great arteries and excessive pulmonary bloodflow remains a challenge. Pulmonary artery banding remains a valuable option, but may induce ventricular hypertrophy, restriction of the bulboventricular foramen and dysplastic changes of the pulmonary valve. These secondary changes might compromise a later Damus-Kaye-Stansel connection because of pulmonary regurgitation but also a subsequent Fontan repair because of ventricular hypertrophy. The aim of this study is to investigate whether a previous pulmonary artery banding might compromise the function of a Damus-Kaye-Stansel connection. METHODS: Thirteen neonates underwent pulmonary artery banding for functionally univentricular heart, transposition of the great arteries and pulmonary hypertension. Coarctation repair was associated in seven patients. All but one survived the operation. The twelve survivors underwent at a second stage a Damus-Kaye-Stansel connection after a mean interval of 1.1 years. The length of this interval was dictated by the degree of ventricular hypertrophy, the restriction of the bulboventricular foramen and by the degree of cyanosis. The Damus-Kaye-Stansel connection was constructed without any foreign material and with resorbable sutures. Associated procedures were: Glenn/hemi-Fontan (8 pts), Blalock-shunt (2 pts), biventricular correction with a homograft (1 pt), Fontan repair (1 pt). Four patients underwent successfully a Fontan repair at a third stage; seven patients are waiting for such repair. RESULTS: All patients survived the second and third stage of this surgical approach. The mean follow-up after the Damus-Kaye-Stansel connection was 2.5 years. Echocardiography at the last follow-up revealed: PR grade 0 (1 pt), grade 1 (8 pts), and grade 2 (3 pts). All patients - except one patient with a systolic gradient of 24 mmHg - had laminar flow without any gradient in the ascending aorta. All patients, including those who underwent a definitive repair, are doing extremely well. CONCLUSION: This experience demonstrates that a neonatal pulmonary artery banding does not compromise the function neither of a Damus-Kaye-Stansel connection nor a Fontan repair.

Management of late complications after classic Fontan procedure by conversion to total cavopulmonary connection.

Classic Fontan procedures, such as atriopulmonary connection or atrioventricular connection, are associated with right atrial dilatation and several late complications. Seven patients with univentricular heart who presented with exercise intolerance (n = 7), severely dilated right atrium (n = 7) with pulmonary vein compression (n = 3), atrial arrhythmias resistant to medical treatment (n = 4), cyanosis (n = 4), diffuse effusions and oedema (n = 1), and protein-losing enteropathy (n = 1), underwent conversion to total cavopulmonary connection 5.8-14.4 years after a previous atriopulmonary connection (n = 6) or atrioventricular connection (n = 1). A 14-year-old boy who, preoperatively, was in ventricular failure and a very poor state died early after conversion because of low cardiac output. All survivors had either marked or partial clinical improvement with regression of cardiomegaly, absence of pulmonary vein compression or cyanosis, and recovery of sinus rhythm. Conversion to total cavopulmonary connection appears to be effective in the treatment of late complications after classic Fontan procedures. It should be considered early in symptomatic patients, before significant ventricular dysfunction and clinical deterioration ensue.

Presenting symptoms and clinical features in 130 patients with the velo-cardio-facial syndrome. The Leuven experience.

During the last 5 years, we diagnosed in Leuven 130 patients with a 22q11 deletion. The deletion was familial in 14 out of 110 index patients (12%), which is significantly less compared to previous studies. In 10 patients, the deletion was maternal, in 4 patients paternal. A cardiac defect was the main presenting symptom in 49% of patients. The other patients were ascertained through developmental delay (16%), behavioural disturbances (7%), otorhinolaryngological manifestations (6%), psychiatric manifestations (3%) and mental retardation (2%). In one patient hypocalcemia was the presenting symptom. In another patient the severe immune deficiency led to diagnosis. Most patients presented a wide variety of the classical features of the Velo-Cardio-Facial syndrome. Velopharyngeal incompetence, learning difficulties or mostly mild mental retardation were almost always present, whereas clinical significant hypocalcemia or immune disturbances were rare. Previously un(der)recognised features include polyhydramnios, renal malformations and laryngotracheamalacia or laryngeal stenosis.

Homograft valve insertion for pulmonary regurgitation late after valveless repair of right ventricular outflow tract obstruction.

OBJECTIVE: Pulmonary regurgitation after valveless repair of right ventricular outflow tract obstruction (RVOTO) results in progressive right ventricular (RV) dilatation and dysfunction in an increasing number of patients. Since 1989, we have exclusively used cryopreserved homografts to restore pulmonary valve competence in these patients. Our 9-year-experience with pulmonary valve insertion (PVI) in such cases has been reviewed to evaluate the indications for this procedure and its benefits. METHODS: From 1989 to 1998, 49 patients (original diagnosis: tetralogy of Fallot in 42 patients and pulmonary stenosis in seven) aged from 3 to 42 years (mean 18 +/- 9 years) underwent PVI with homografts late (mean 13 +/- 7 years) after valveless repair of RVOTO (transannular patch, n = 38; pulmonary valvulotomy therefore tau chi infundibular patch, n = 11). Preoperatively, all patients had severe pulmonary regurgitation, cardiomegaly, significant to severe RV dilatation and dysfunction, fatigue, reduced exercise tolerance, and were in NYHA class II (n = 43) or III (n = 6). Ten patients had ventricular arrhythmia. RESULTS: There was one early death, due to air embolism, and one late death, due to ventricular arrhythmia. All survivors but one, who subsequently underwent heart transplant, had symptomatic improvement after homograft insertion. The mean RV end-diastolic diameter decreased from 38 +/- 9 to 26 +/- 8 mm (P < 0.01), and cardiothoracic ratio decreased from 0.62 +/- 0.07 to 0.54 +/- 0.04 (P < 0.01). Good late homograft function was the rule, with all the survivors being free of reoperation for valve failure. At a mean follow-up of 42 +/- 28 months, 41 patients (87% of the survivors) were in New York Heart Association (NYHA) class I and six in class II. Within this group three patients are still in treatment for RV failure and five for ventricular arrhythmias. In these patients, the average interval between RVOTO repair and PVI was significantly longer than in the others (18 +/- 7 vs. 12 +/- 6 years, P < 0.01). CONCLUSION: Homograft PVI is safe and provides clinical improvement with a significant reduction in RV volume overload and excellent mid-term results in most patients with severe PR late after RVOTO repair. This procedure should be undertaken early in symptomatic patients, before severe RV failure and ventricular arrhythmias ensue.

Delineation of the critical deletion region for congenital heart defects, on chromosome 8p23.1.

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.

Velocardiofacial syndrome patients with a heterozygous chromosome 22q11 deletion have giant platelets.

Patients with a microdeletion on chromosome 22q11 demonstrate the clinical picture of the velocardiofacial syndrome. We report on three members of the same family with this microdeletion and velocardiofacial syndrome, all having an increase in platelet size and a mild decrease in platelet number. Their platelet function, however, tested by aggregation and by adherence to collagen in a whole blood perfusion system, was normal. We retrospectively studied the files of 35 other patients with 22q11 deletion and also found that their platelets had an increased size compared with cardiac controls. Moreover, their platelet size correlated negatively with platelet number. Knowing that patients with 22q11 deletion are obligate carriers for a heterozygous glycoprotein Ib beta deletion, these patients can be considered to be heterozygous Bernard-Soulier patients. In addition, a significant increase in platelet size may be a positive predictor for the clinical diagnosis of the velocardiofacial syndrome.