Congenitally palliated scimitar syndrome.

We present a rare case of scimitar syndrome in which the scimitar vessel, collecting all the right pulmonary veins, was stenotic at its junction, with the inferior caval vein and two anomalous vessels, connecting to the same venous collector, draining most of the flow to the left atrium. We arbitrarily defined this rare anatomical variant as a congenitally palliated scimitar syndrome.

Recommendations from the Association of European Paediatric Cardiology for training in diagnostic and interventional cardiac catheterisation.

Cardiac catheterisation in congenital heart disease is a developing field. Patients' ages range from foetus to adulthood. This document is a revision and update of the previously published recommendations and summarises the requirements for training in diagnostic and interventional cardiac catheterisation.

[Prevalence, mortality and lethality of congenital heart defects from the Tuscan Registry (Tuscany Region, Central Italy), 1992-2009]. / Prevalenza, mortalità e letalità dei difetti cardiaci congeniti dal Registro toscano, 1992-2009.

OBJECTIVES: to estimate prevalence, mortality and lethality of congenital heart defects (CHDs), and to evaluate time trend by comparing two birth cohorts (1992- 2000 vs. 2001-2009). DESIGN: descriptive study using a population-based registry: the Tuscan Registry of congenital defects (RTDC), which is a member of the European network of surveillance of congenital anomalies (EUROCAT) since 1979. SETTING AND PARTICIPANTS: CHD cases were collected by the RTDC between 1992 and 2009. MAIN OUTCOME MEASURES: prevalence and mortality rates were calculated for all and non-chromosomal CHDs. The non-chromosomal cases were classified in three severity classes (SI, SII, SIII), according to decreasing perinatal mortality. It was estimated prevalence of: live births, foetal deaths (stillbirths and spontaneous abortions from 20 weeks gestation), terminations of pregnancy for foetal anomaly (TOPFAs) at any gestational age, and of prenatally diagnosed cases. Perinatal, neonatal and infant mortality were calculated. Early-neonatal, neonatal and infant lethality were calculated for the non-chromosomal cases. RESULTS: 3,653 cases were identified out of 486,947 live births and 1,883 stillbirths, 95% of which were non-chromosomal cases. The total average prevalence was 7.47/1,000 births. The overall prevalence decreased significantly in all CHDs (Prevalence ratio - PR: 0.86; 95%CI 0.80-0.91) as well as in non-chromosomal (PR: 0.86; 95%CI 0.80-0.92), while in the more severe defects (SI/SII combined cases) the total prevalence was stable over time. In more severe cases, prevalence of live births decreased significantly (PR: 0.83; 95%CI 0.71-0.97), while the greater increase of TOPFAs and of diagnosed cases was observed in the prenatal period. All three mortality rates reduced significantly over time. In the more severe cases, the greatest rate mortality reduction was observed for neonatal mortality (Mortality ratio - MR: 0.29; 95%CI 0.16-0.49) than perinatal (MR: 0.37; 95%CI 0.19-0.70) and infant mortality (MR: 0,40; 95%CI 0.28-0.56). In this group of CHDs, early neonatal lethality decreased from 10% to 3%, neonatal lethality from 17% to 6%, and infant lethality from 24% to 10%. CONCLUSIONS: the results suggest that the improvements in prenatal diagnosis and in foetal and neonatal treatment and care have reduced the burden of congenital heart defects on the health of the Tuscany population.

Melody transcatheter pulmonary valve implantation. Results from the registry of the Italian Society of Pediatric Cardiology.

BACKGROUND AND AIMS: Percutaneous implantation of pulmonary valve has been recently introduced in the clinical practice. Our aim was to analyze data of patients treated in Italy by using the Melody Medtronic valve. METHODS: Prospective, observational, multi-centric survey by means of a web-based database registry of the Italian Society of Pediatric Cardiology (SICP). RESULTS: Between October 2007 and October 2010, 63 patients were included in the registry (median age: 24 years; range 11-65 years). Forty subjects were in NYHA class I-II while 23 were in NYHA class III-IV. Patients included had a history of a median three previous surgeries (range 1-5) and a median of one previous cardiac catheterization (range 0-4). A cono-truncal disease was present in 39 patients, previous Ross operation in 9, and other diagnosis in 15. Indication to valve implantation was pure stenosis in 21 patients, pure regurgitation in 12, association of stenosis and regurgitation in 30. Implantation was performed in 61 subjects (97%). Pre-stenting was performed in 85% of cases. Median procedure time was 170 minutes (range 85-360). No significant regurgitation was recorded after procedure while the trans-pulmonary gradient reduced significantly. Early major complications occurred in seven subjects (11%). One death occurred in the early post-operative period in a severely ill subject. At a median follow-up of 30 months (range 12-48 months), three patients died due to underlying disease. Major complications occurred in six patients during follow-up (external electric cardioversion: one patient; herpes virus encephalitis: two patients; Melody valve endocarditis needing surgical explant: two patients; major fractures of the stent and need second Melody valve implantation: two patients). Freedom from valve failure at latest follow-up was 81.4% ± 9%. CONCLUSION: Early results of the SICP registry on transcatheter Melody pulmonary valve implantation show that the procedure is safe and successful. Major concerns are related to the occurrence of stent fracture and bacterial endocarditis. Longer follow-up and larger series are needed.

Residual shunt after patent foramen ovale closure: preliminary results from Italian patent foramen ovale survey.

BACKGROUND: Percutaneous patent foramen ovale (PFO) closure is accepted as treatment for cryptogenic ischemic stroke/transient ischemic attack in young subjects. However, a thorough evaluation of residual right-to-left shunt (rRLS) after PFO closure is needed. Our aims were to analyze the characteristics related to PFO diagnosis and closure, focusing on rRLS and clinical recurrences until 24-month follow-up. Data were extrapolated from the 12-month Italian PFO Survey. METHODS: In all, 1035 patients were included. PFO diagnosis and right-to-left shunt (RLS) were assessed by contrast-enhanced transesophageal and/or transthoracic echocardiography and/or transcranial Doppler. RESULTS: PFO diagnosis with RLS data were available in 894 of 1035 (86.4%) patients. rRLS was investigated in 49.6% (6 months), 27.1% (12 months), and 3.5% (24 months), and observed in 19.5% (6 months) and 18.2% (12 months) of subjects. Large permanent rRLS was observed in less than 3% of RLS-positive patients after 1 year. Eleven of 14 and 3 of 14 neurological recurrences were observed in 10 of 444 (2.25%) and 2 of 243 (0.8%) patients within the 6- and 12-month follow-up, respectively. Among these, no large rRLS was reported. There were no neurological events at 2-year follow-up. Forty of 444 subjects had non-neurological complications, mostly cardiac arrhythmias within the sixth month. CONCLUSIONS: PFO closure is a safe procedure. rRLS is not uncommon but large rRLS is rare. Clinical complications, mostly related to cardiac arrhythmias, are not unusual. Evaluation of the data of the whole survey is underway.

The combined use of neutrophil gelatinase-associated lipocalin and brain natriuretic peptide improves risk stratification in pediatric cardiac surgery.

BACKGROUND: The aim of this study is to test the hypothesis whether the combined use of a cardio-specific biomarker, the brain natriuretic peptide (BNP) and a marker of early renal damage, the assay of urinary neutrophil gelatinase-associated lipocalin (uNGAL), may improve risk stratification in pediatric cardiac surgery. METHODS: We prospectively enrolled 135 children [median age 7 (interquartile range 1-49) months] undergoing to cardiac surgery for congenital heart disease. All biomarkers were evaluated pre- and post-operatively at different times after cardiopulmonary-bypass (CPB): uNGAL at 2, 6 and 12 h; BNP at 12 and 36 h; serum creatinine at 2, 6, 12, and 36 h. Primary endpoints were development of acute kidney injury (AKI) (defined as 1.5 serum creatinine increase) and intubation time. RESULTS: AKI occurred in 39% of patients (65% neonates and 32% older children, p=0.004). The peak of uNGAL values occurred more frequently at 2 h. uNGAL values at 2 h [median 28.2 (interquartile range 7.0-124.6) ng/L] had a good diagnostic accuracy for early diagnosis of AKI with an AUC (area under the curve) ROC (receiver operating characteristic) curve of 0.85 (SE 0.034). Using multivariable logistic regression analysis, development of AKI was significantly associated with uNGAL values at 2 h after CPB [OR=1.88 (1.30-2.72, p=0.001)], together with the CPB time and Aristotle score, as an index of complexity of the surgical procedure, while pre-operative BNP values were not. Furthermore, uNGAL and pre-operative BNP values (together with Aristotle score) were significantly associated with adverse outcome (longer intubation time and mortality). CONCLUSIONS: Pre-operative BNP and uNGAL values after surgery (together with the Aristotle score) were independently associated with a more severe course and worse outcome in children undergoing cardiac surgery for congenital heart disease.

Stenting of aortic coarctation and exercise-induced hypertension in the young.

OBJECTIVES: To evaluate whether the stenting of aortic coarctation enhance the risk of exercise-induced hypertension (EIH). BACKGROUND: There is the theoretical concern that aortic stents may cause increased aortic wall impedance and therefore systolic hypertension during exercise. METHODS: Blood pressure and the Doppler derived peak and mean systolic pressure gradient (PSG and MSG) across the distal aorta at the peak of exercise were evaluated in young patients (mean age 14 +/- 3 years) with aortic coarctation successfully treated with surgery or with stent implantation at least 1 year before the test. Only patients who reached the 85% maximal predicted heart rate or whose exercise test was interrupted because of severe hypertension, and in whom significant aortic narrowings were excluded by a MRI or a CT scan performed in the six months preceding the exercise test were included in the study. RESULTS: Seventeen patients formed the surgery-group, while 15 patients the stent-group. Patients in surgery-group were younger at coarctation repair and with a longer follow-up than those in stent-group. No difference was present regarding age, body surface area, gender, and presence, and degree of mildly hypoplastic aortic segments between the two groups as well as between patients with or without EIH. EIH was found in 35% of surgery-group patients and in 33% of stent-group patients. PSG and MSG were similar in the patients with or without EIH. CONCLUSIONS: EIH can be found in a high number of young patients successfully treated for aortic coarctation but at intermediate follow-up stent implantation does not seem to enhance the risk of EIH.

Interventional cardiac catheterization in neonatal age: results in a multicentre Italian experience.

BACKGROUND: Despite recent technical advances, interventional cardiac catheterization is still challenging in neonatal age and no specific data concerning early outcome are so far published in literature. METHODS: Neonatal trans-catheter cardiac interventions performed in high-volume Italian referral centers were retrospectively analyzed. Primary outcomes were procedural major adverse events, in-hospital mortality and procedural failure. Secondary outcomes were minor adverse events and need for blood transfusion. RESULTS: From January 2000 to December 2017, 1423 newborns (mean weight 3.0 ± 0.6 kg, range 1.0-5.8; median age 2.0 days) underwent interventional cardiac catheterization. Overall, global procedure adverse event rate and in-hospital mortality were 10.2% and 5.2%, respectively. At multi-variable analysis, primary composite outcome was significantly related to low-weight (<2.5 kg) (p < 0.01) and younger age (≤7 days) (p < 0.01) at the procedure, prematurity (p < 0.01), uni-ventricular physiology (p < 0.01), associated genetic syndromes (p < 0.01) and procedure risk category (p < 0.01). No relationship between volume of activity of any single center and procedure outcome was found. Over time, a trend toward an increased number of procedures and their complexity was recorded. Trans-catheter management of cardiac malformations with critical, duct-dependent pulmonary blood flow by arterial duct stenting or right ventricular outflow tract stenting showed the highest increase. CONCLUSIONS: Interventional cardiac catheterization is relatively safe and feasible in neonatal age. Peri-natal age, low weight, uni-ventricular physiology and genetic syndromes still significantly contribute to procedural morbidity and in-hospital mortality of this approach.

DATA in BRIEF of: Interventional Cardiac Catheterization in Neonatal Age: Results in a Multi-centre Italian Experience.

A comprehensive description of morbidity and mortality as well as risk factors of interventional cardiac catheterization performed in neonatal age was reported in our paper recently published on the International Journal of Cardiology (IJCA28502; PII: S0167-5273(20)30384-3; DOI: 10.1016/j.ijcard.2020.04.013). Eight Italian high-volume centres of Paediatric Cardiology were involved in this observational, retrospective data collection and analysis. In this dataset, clinical and procedural characteristics of 1423 newborns submitted to 1551 interventional cardiac catheterization procedures were analyzed. Primary outcomes were considered procedure and in-hospital mortality as well as major adverse event and procedural failure rates. Secondary outcomes were considered minor adverse events and need for blood transfusion. Targets of this data analysis were: 1) to evaluate the overall major risk factors of interventional cardiac catheterization; 2) to identify the most hazardous interventional procedures; 3) to assess possible trends of individual procedures as well as their outcome over time; 4) to find possible relationships between the volume activity of any centre and the procedure and follow-up outcome. In particular, this Data in Brief companion paper aims to report the specific statistic highlights of the multivariable analysis (binary logistic regression) used to assess the impact of any potential risk factors on the type of procedure over a short-term follow-up.

[Patent foramen ovale: "les liaisons dangereuses" between anatomy and genetics]. / Forame ovale pervio: le relazioni pericolose fra anatomia e genetica.

We reported a case of two 24-year-old and 17-year-old male patients with episode of transient ischemic attacks and diagnosed as having patent foramen ovale (PFO). One patient had heterozygosity for the factor V Leiden mutation, and one other had heterozygosity for prothrombin G20210A mutation. Both of them were also carriers for MTHFR 677T genotype with elevated plasma levels of homocysteine (22.3 +/- 3.9 micromol/L). These findings strongly confirm and emphasize the importance of the genetic screening for thrombotic mutations in young patients with PFO-related ischemic events in order to improve secondary prevention strategies.

Optimus covered stent: Advanced covered stent technology for complex congenital heart disease.

AIM: To assess the acute results of the first human use of the Optimus covered stent in complex coarctation of the aorta. METHODS AND RESULTS: We successfully implanted the Optimus covered stent in eight cases in patients whose preprocedural anatomy looked challenging for currently available covered stents. Six of the patients had native coarctation with one recoarctation following surgical repair. There were no significant complications with reduction in the mean invasive gradient from 22 to 1 mm Hg. The length of stents used ranged from 33 to 57 mm with a median shortening after expansion of 13%. Postprocedural follow-up with magnetic resonance imaging or computed tomography has not shown evidence of fracture or migration or renarrowing. The median duration of follow-up is 10 months. CONCLUSIONS: Preliminary results show that the Optimus covered stent is safe and efficacious for use in patients with coarctation of challenging morphology. A systemic trial will be required to evaluate this stent for more widespread practice.

Sex differences for major congenital heart defects in Down Syndrome: A population based study.

BACKGROUND: Down syndrome (DS) is the most common autosomal chromosomal anomaly in liveborn infants. About 40% of infants with DS have a major congenital heart defect (CHD). Among them, atrioventricular septal defects (AVSD), atrial septal defects (ASD), ventricular septal defect (VSD) and Tetralogy of Fallot (ToF) are the most common. The aim of this study was to estimate the sex difference in the occurrence of CHD in infants with DS comparing it with non-DS infants. METHOD: Live birth cases of DS diagnosed by the first year of life were extracted from the Registry of Congenital Anomalies of Tuscany (2003-2015 period). CHDs associated with DS were detected both from the registry and the hospital discharge data. Sex differences in total CHDs and ASD, VSD, AVSD, severe CHDs, ToF subgroups were investigated. Relative Risks between males and females (RRMF) with p-values and 95% confidence interval (95% CI) were estimated. RRMF of CHD in infants with DS was compared to RRMF in infants without DS. The ratio between relative risks (RRR) was estimated. RESULTS: A total of 230 live birth cases of DS were analyzed, with a prevalence of 5.70 per 10,000 births. Sex ratioMF was 1.3. One hundred and one DS cases (43.9%) were associated with at least one CHD. Among them, CHDs are more frequent in females (total CHD: RRMF = 0.62; 95% CI: 0.46-0.83, ASD: RRMF = 0.40; 95% CI: 0.21-0.77, severe CHD: RRMF = 0.58; 95% CI: 0.35-0.95, AVSD: RRMF = 0.57; 95% CI: 0.32-1.00, VSD: RRMF = 0.59; 95% CI: 0.35-1.00). Four cases of ToF were observed (all males). Sex difference was more evident in DS than in non-DS infants (RRR = 0.63; 95% CI: 0.52-0.77), in particular for severe CHDs (RRR = 0.38; 95% CI: 0.25-0.57). CONCLUSION: The increased sex difference for CHDs in DS suggests a possible role of sex as effect modifier in the association between DS and CHD. The results enforce the evidence on sex differences for CHDs in DS and can stimulate future genetic research activities.

Echocardiographic nomograms for upper abdominal aorta Doppler systolic wave values and systo-diastolic diameters variations in children.

BACKGROUND: Abdominal aorta pulsatility and blood flow patterns are important diagnostic indicators in congenital heart disease. Reference values for these indexes are lacking. METHODS: We prospectively studied abdominal aorta pulsed-wave Doppler systolic peak velocity, deceleration time, and wave duration, and two-dimensional vessel diameters in systole and diastole in healthy Caucasian children. Heteroscedasticity was accounted for by White or Breusch-Pagan test. Age, weight, height, heart rate (HR), and body surface area (BSA) were used as independent variables in different analyses to predict the mean values of each measurement. Structured Z-scores were then computed. RESULTS: In all, 853 subjects (age 0 days to 17 years; 45% females; BSA 0.12-2.12m2) were studied. The predicted values and Z-score boundaries are presented. Data are also presented as mean±2 SDs for a given BSA. CONCLUSIONS: We report paediatric echocardiographic nomograms for multiple proximal abdominal aorta parameters including pulsed-wave Doppler systolic velocities, deceleration time, wave duration, and two-dimensional vessel diameter variations. Significant variations in these functional indexes with age were found that should be taken into account in clinical practice. At lower ages, steeper and shorter pulsed-wave Doppler peak velocity and limited pulsatility should be expected as physiologic findings.

Incidence and natural history of neonatal isolated ventricular septal defects: Do we know everything? A 6-year single-center Italian experience follow-up.

BACKGROUND: Despite ventricular septal defects (VSDs) are the most common congenital heart diseases (CHDs) in the neonatal period, their incidence and natural history are still debated and their follow-up and management strategies remain controversial. Our aim was to evaluate the incidence and natural history of isolated VSDs. METHODS: From January 1996 to December 2015 all neonates with a CHD suspicion were referred to the Cardiological Department of Grosseto Misericordia Hospital. Only newborns with confirmed isolated VSD were enrolled in this study and followed for 6 years. RESULTS: Our 343 newborns with an isolated VSD (incidence of 10.45/1000/births) account for 64% of all detected CHDs. VSDs location were as follows: muscular (73.8%), perimembranous (11.3%), inlet (1%), and outlet (0.8%). Of the located VSDs, 90% were small, 7.5% moderate, and 2.5% large, respectively. Spontaneous closure was observed in 96 (29.2%) of the VSD patients at 6-month, 198 (60.2%) at 1-year, 261 (79.3%) at 2-year, and in 302 (91.8%) at 6-year follow-up. Risk factors for defect persistence were a perimembranous location (P = .001; HR: 0.508, CI: 0.342-0.755), detection of multiple defects (P = .043; HR: 0.728, CI: 0.536-0.990), and male gender (P < .048; HR: 0.783, CI: 0.615-0.998), respectively. CONCLUSIONS: We here provide an incidence and natural history of neonatal isolated VSDs in a neonatal Caucasian population. These data may be useful for the development of expert consensus/standard recommendation guidelines for the follow-up and VSD management, data that are currently lacking.

Prothrombotic mutations as risk factors for cryptogenic ischemic cerebrovascular events in young subjects with patent foramen ovale.

BACKGROUND AND PURPOSE: Patent foramen ovale (PFO) has been identified as a potential risk factor for cerebrovascular ischemia. Procoagulant mutations may increase the risk and impact the choice of appropriate therapy for secondary prevention. We evaluated the prevalence of the 2 most common genetic risk factors for thromboembolism, factor V Leiden (G1691A) and prothrombin G20210A, in young PFO patients who were referred for percutaneous transcatheter closure of their PFO. METHODS: Ninety-seven patients (50 men; mean+/-SD age, 40.9+/-10.0 years) with first-ever cerebrovascular events before the age of 55 years and 160 age-matched control subjects (69 men; mean+/-SD age, 40.4+/-10.5 years) were recruited into the study. Factor V Leiden and prothrombin G20210A mutations were detected by using a multiplex allele-specific polymerase chain reaction assay. RESULTS: The prevalence of subjects carrying at least 1 prothrombotic genotype was significantly higher in the group of PFO patients than in the group of controls (10.3% vs 2.5%; chi(2)=7.2, P=0.008). Two patients (2.1%) versus 1 control subject (0.6%) and 8 cases (8.2%) versus 3 controls (1.9%) were carriers for factor V Leiden and prothrombin G20210A mutations, respectively. After adjustment for other vascular risk factors, the combination of either factor V Leiden or prothrombin G20210A and PFO was associated with a 4.7-fold (95% CI=1.4 to 16.1; P=0.008) increased risk of cerebral ischemia in young patients. CONCLUSIONS: Our results indicate that prothrombotic mutations are important risk factors for cerebral ischemia in young patients with PFO. Screening for thrombotic mutations should be considered in young patients with PFO-related ischemic events.

Nomograms for two-dimensional echocardiography derived valvular and arterial dimensions in Caucasian children.

BACKGROUND: Despite recent advances, current pediatric echocardiographic nomograms for valvular and arterial dimensions remain limited. METHODS: We prospectively studied healthy Caucasian Italian children by two-dimensional (2D) echocardiography. Echocardiographic measurements for 18 valvular and arterial dimensions were performed and models were generated testing for linear, logarithmic, exponential, and square root relationships. Heteroscedasticity was accounted for by White or Breusch-Pagan test. Age, weight, height, heart rate, and body surface area (BSA) were used as independent variables in different analyses to predict the mean values of each measurement. Structured Z-scores were then computed. RESULTS: In all, 1151 subjects (age 0 days to 17 years; 45% females; BSA 0.12-2.12m2) were studied. The Haycock formula was used when presenting data as predicted values (mean±2 SDs) for a given BSA and within equations relating echocardiographic measurements to BSA. The predicted values and Z-score boundaries for all measurements are presented. CONCLUSIONS: We report echocardiographic nomograms for valvular and arterial dimensions derived from a large population of children. Integration of these data with those of previous reports would allow for a comprehensive coverage of pediatric 2D echocardiographic nomograms for measurement of 2D cardiac structures.

Major Aortopulmonary Collaterals in Transposition of the Great Arteries: A Cause for Preoperative and Postoperative Hemodynamic Imbalance.

We describe a case of transposition of the great arteries (TGA) with significant aortopulmonary collateral vessels causing management difficulties before and after an arterial switch operation. Preoperatively, the presence of collaterals exacerbated aortic diastolic runoff and led to myocardial ischemia. Postoperatively, despite uneventful extubation, the infant developed clinical heart failure characterized by pericardial and pleural effusions and feeding difficulties, which promptly resolved with percutaneous embolization of collaterals. Major aortopulmonary collaterals are rarely associated with TGA, but if present they may cause important hemodynamic imbalance in infants with TGA.

Nomograms for mitral inflow Doppler and tissue Doppler velocities in Caucasian children.

BACKGROUND: Pediatric echocardiographic nomograms for systolic/diastolic functional indices are limited by small sample size and inconsistent methodologies. Our aim was to establish pediatric nomograms for mitral valve (MV) pulsed wave Doppler (PWD) and tissue Doppler imaging (TDI) velocities. METHODS: We performed PWD/TDI measurements of MV velocities and generated models testing for linear/logarithmic/exponential/square root relationships. Heteroscedasticity was accounted for by White test or Breusch-Pagan test. Age, weight, height, heart rate (HR), and body surface area (BSA) were used as independent variables in different analyses to predict the mean values of each measurement. RESULTS: In all, 904 Caucasian Italian healthy children (age 0 days-17 years; 45.5% females; BSA 0.12-2.12m(2)) were prospectively studied. No individual variable provided equations with an acceptable coefficient of determination (R(2)) and even the inclusion of multiple variables in the model resulted in only a partial amelioration of the R(2). Higher R(2) were obtained for PWD-E deceleration time (0.53), septal (Se') and lateral (Le') MV-TDI e' velocity (Se': 0.54; Le': 0.55). Variability was higher at lower age and BSA. In older children patterns were more reproducible; however, the exclusion of neonates did not substantially improve the final models. The low R(2) hampered building of z-scores and calculation of estimated percentiles. Thus normative data have been presented as observed percentile according to age for all measurements. CONCLUSIONS: We report normal ranges for PWD and TDI mitral velocities derived from a large population of Caucasian children. Variability of diastolic patterns especially at lower ages needs to be taken into account.

Molecular characterization of 22q11 deletion in a three-generation family with maternal transmission.

Haploinsufficiency of chromosome 22q11.2 is a well-established cause of both the DiGeorge anomaly and the velocardiofacial syndrome. This condition shows a continuous spectrum of phenotypic manifestations with a considerable inter- and intrafamilial variability. We report on a three-generation family with four members sharing the same 3 Mb long deletion but showing different phenotypic expression. In the first generation, the deleted patient has hypernasal speech and suffers from recurrent psychotic episodes. Two of her offspring inherited the deletion. One of these, a male, has hypernasal speech, low-set ears, hypocalcemia, severe development delay, and tetralogy of Fallot. The other, a female, has hypernasal speech, minor facial anomalies, and very mild mental retardation. Her daughter has tetralogy of Fallot, velopharyngeal insufficiency, and mild facial anomalies. This family is an example of the widely variable phenotypic expressivity of the 22q11.2 deletion. There is no correlation between the size of the deletion and the phenotypic manifestations. Genetic background and/or environmental factors could explain the different phenotypes observed in the affected members of the family.