Ventricular septal defect in Down syndrome. Anatomic types and associated malformations

Ventricular septal defect is a common cardiac anomaly in Down syndrome. To detect the prevalence of anatomic types and associated cardiac malformations we analyzed the echocardiographic and angiocardiographic findings of 73 children with ventricular septal defect and Down syndrome. We compared these results with those obtained in 303 patients with ventricular septal defect without Down syndrome. The prevalence of inlet ventricular septal defect was significantly higher in patients with Down syndrome, while muscular and subpulmonary ventricular septal defects were present only in patients without Down syndrome. The incidence of a cleft of the mitral valve was significantly higher in Down syndrome, while left-ventricular inflow and outflow obstructions were present only in patients without Down syndrome. Different patterns of ventricular septal defect and associated anomalies exist in patients with and without Down syndrome.     

Atrioventricular canal in Down syndrome. Prevalence of associated cardiac malformations compared with patients without Down syndrome

The atrioventricular canal is the "classic" congenital heart anomaly in Down syndrome. We may learn more of the nature of this disorder by careful study of the anatomic characteristics of the cardiac lesions and by comparing these lesions in patients with and patients without Down syndrome. We reviewed the clinical characteristics (echocardiographic and angiocardiographic) of 220 patients with atrioventricular canal and compared the prevalence of anatomic types and associated cardiac malformations in children with (105) and without (115) Down syndrome. In patients with Down syndrome, the complete form of atrioventricular canal was prevalent, with a high frequency of associated Fallot's tetralogy. Partial atrioventricular canal and left-sided anomalies were more common in patients without Down syndrome. Down syndrome is associated with a simpler type of atrioventricular canal when compared with patients with a normal chromosome configuration.     

Stenosis of pulmonary veins in Down syndrome

Two patients with Down syndrome, intracardiac communications and elevated pulmonary arteriolar resistance presented early in life. Both patients had significant stenosis of pulmonary veins. The progressive nature of the stenosis is illustrated in one patient. Pulmonary venous stenosis in Down syndrome has been recorded only twice before in the literature, and may play a part in the early onset of pulmonary vascular occlusive disease in some patients.     

Cholelithiasis in infants with Down syndrome. Three cases and literature review.

Only four cases of cholelithiasis have been reported in patients with Down syndrome and none in Down syndrome infants. The cases of three Down syndrome infants (all males) with cholelithiasis are reported. Each exhibited different fetal complications, and in each, Down syndrome was diagnosed at birth. Gallstones apparently were congenital (a rarity) in one infant, since they were detected on the first day of life. Cholelithiasis was an incidental finding in another of the infants when, at 12 weeks old, he had renal ultrasonography because of a urinary tract infection. The third infant was 4 months old when sonographic studies revealed a gallstone. Despite the confirmation of cholelithiasis in all three infants, none has since had any signs or symptoms that suggest the need for intervention. Cholelithiasis is probably more common in Down syndrome infants than has been supposed, but whether Down syndrome infants with gastrointestinal (GI) malformations are more likely to have gallstones than are children with similar GI malformations but with normal karyotypes is unknown.     

Cardiovascular disease in Down syndrome

This article focuses on the clinical evaluation of children with cardiovascular diseases associated with Down syndrome. Recent advances in diagnosis and management are discussed and the medical or surgical approach to the patient with severe cardiovascular malformations is presented.     

Clinical and sonographic features of pediatric soft-tissue vascular anomalies part 2: vascular malformations

Vascular malformations are a heterogeneous group of entities, many of which present in the pediatric age group. Sonography plays a major role in the management of children with these vascular anomalies by providing information that helps in diagnosing them, in assessing lesion extent and complications, and in monitoring response to therapy. The interpretation of sonographic findings requires correlation with clinical findings, some of which can be easily obtained at the time of scanning. This has to be combined with the use of appropriate nomenclature and the most updated classification in order to categorize these patients into the appropriate management pathway. Some vascular malformations are part of combined vascular anomalies or are associated with syndromes that include other disorders, frequently limb overgrowth, and these are now being reclassified based on their underlying genetic mutation. Sonography has limitations in the evaluation of some vascular malformations and in these cases MR imaging might be considered the imaging modality of choice, particularly for lesions that are large, that involve multiple compartments or are associated with other soft-tissue and bone abnormalities. In this article, which is part 2 of a two-part series, the authors review the most relevant clinical and sonographic features of arteriovenous, capillary, venous and lymphatic malformations as well as vascular malformations that are part of more complex conditions or associated with syndromes, including Parkes–Weber syndrome, phosphatase and tensin homologue (PTEN) hamartoma tumor syndromes, Klippel–Trénaunay syndrome, CLOVES (congenital lipomatous overgrowth, vascular malformations, epidermal nevi and skeletal anomalies) syndrome, fibro-adipose vascular anomaly and Proteus syndrome.     

Cystic hygroma of the neck and non-immunologic hydrops fetalis

Fetal cystic hygromas are a manifestation of early lymphatic obstruction. They are mostly associated with nonimmune hydrops fetalis. They often occur in a number of chromosome abnormalities (Turner syndrome and Down syndrome). We report on a prenatally detected case with nuchal cystic hygroma and nonimmune hydrops fetalis without chromosome aberration and without further major malformations. Postnatally hygroma and hydrops regressed.     

Peripheral stenoses of the pulmonary arteries: possible causes and syndromic relationships (author's transl)]

The catheterization results and additional malformations and diseases in 20 infants and children with pulmonary artery stenosis are reported. In 17 cases additional cardiovascular malformations were found. In 15 cases extracardiac malformations or developmental retardation were observed. Peripheral stenoses of the pulmonary arteries are frequently established in rubella embryopathy, in the syndrome of supravalvular aortic stenosis, in Down s syndrome, in different types of nanism, in thalidomide embryopathy and in the socalled arteriohepatic dysplasia (Watson and Miller) associated with hypoplasia of the bile ducts. In 3 cases an arteriophepatic dysplasia was confirmed by angiocardiography and biopsy. Coarctations of pulmonary arteries rarely need operative interventions.     

Blue rubber bleb nevus syndrome with knee joint disorder

Blue rubber bleb nevus syndrome (BRBNS) involves cutaneous vascular malformation characterized by multiple venous malformations. This commonly affects the skin and gastrointestinal tract. BRBNS is associated with anemia and occasionally involves orthopedic manifestations. A 6‐year‐old boy was referred to hospital for evaluation of anemia. He presented with a rubber‐like soft‐tissue mass in the left knee and the right side of the neck, recurrent pain, and fixed flexion contracture of the knee. Blood examination indicated consumption coagulopathy and anemia caused by not only iron‐deficiency anemia but also microangiopathy. Endoscopy of the gastrointestinal tract indicated multiple bluish‐black sessile venous malformations. Ultrasonography and magnetic resonance imaging of the knee showed intra‐articular and intramuscular involvement. Based on these findings, BRBNS with knee joint disorder was diagnosed. With regard to vascular malformations, like other diseases such as inflammatory arthropathy, ultrasonography of the joint may become a new diagnostic approach for evaluating orthopedic manifestations.     

Prune belly syndrome

Prune belly is a lax, wrinkled abdominal wall and frequently is associated with other anomalies. The prune belly syndrome is a specific constellation of anomalies consisting of an abdominal wall deficient in muscular tissue, dilated urinary tract, and bilateral cryptorchidism. This group of anomalies is also called the Eagle-Barrett syndrome and the triad syndrome. In about 3 of 4 patients with the prune belly syndrome, there are associated malformations of the cardiopulmonary, gastrointestinal, and orthopedic systems.     

Altered expression patterns of EphrinB2 and EphB2 in human umbilical vessels and congenital venous malformations

Vascular malformations cause discomfort and pain in children and are often associated with skeletal hypertrophy. Their molecular basis is poorly understood. Ephrin ligands and Eph receptor tyrosine kinases are involved in embryonic vascular development. In mice, some ephrin/Eph family members show a complementary expression pattern in blood vessels, with ephrinB2 being expressed on arterial and EphB4 on venous endothelium. Targeted deletions of the genes reveal their essential roles for conduit vessel development in mice, suggesting similar functions during human vascular development and deregulation in vascular malformations. Here, we have defined the expression patterns of human ephrinB2, EphB4, and EphB2 in normal vessels of neonates (i.e. umbilici) and adults and compared them with those in congenital venous malformations. In adults, normal vessels of the skin, muscle, and legs express ephrinB2 and EphB2 on arterial endothelial cells (ECs), whereas EphB4 is found in arteries and veins. In the umbilicus, EphB2 is a specific marker of arterial ECs, whereas ephrinB2 is additionally expressed in venous ECs, suggesting an arterial function of the veins. In venous malformations, the expression of EphB4 is not altered, but both ephrinB2 and EphB2 are ectopically expressed in venous ECs. This may reflect a nonphysiologic arterialization of malformed veins. Our study shows that the arterial markers ephrin B2 and EphB2 are expressed in a subset of veins, and it remains to be studied whether this is cause or consequence of an altered vascular identity.     

Cervicofacial vascular anomalies. II. Vascular malformations

Vascular malformations are the second major category of vascular anomalies. In contrast to vascular tumors, they are present at birth and grow commensurately with the child. Although the molecular mechanisms underlying the formation of these lesions remain unclear, lesions are known to result from abnormal development and morphogenesis. Histologic examination of vascular malformations shows no evidence of cellular proliferation, but rather progressive dilation of abnormal channels. Vascular malformations are designated according to their predominant channel type; they may be capillary, venous, lymphatic, arterial, and combined malformations. Malformations with an arterial component are rheologically fast-flow, whereas capillary, lymphatic, and venous malformations are slow-flow in nature. The morbidity of vascular malformations varies greatly both within and among the clinical subgroups cited above. This article describes the clinical presentation, diagnosis, and management of vascular malformations. The more frequently encountered clinical presentations involving the head and neck are highlighted.     

Congenital heart disease in Down syndrome: an echocardiographic study.

We evaluated the utility of echocardiography in assessing the frequency and nature of cardiac malformations in children with Down syndrome. Fifty cases of chromosomally proven Down syndrome were studied. A physical examination, electro cardiogram, radiograph of chest and two-dimensional echocardiography was performed on all patients. Twenty-two (44%) children had heart diseases. Endocardial-cushion-defect was the commonest anomaly, followed by ventricular septal defect. Three children with heart disease were asymptomatic and had normal X-ray films of chest and ECGs. The prevalence and specific type of congenital heart disease in this study is comparable to the studies using invasive means for diagnosis. The study further suggests that clinical examination of the cardiovascular system alone may not be sufficient in detecting heart disease. Two-dimensional echocardiography offers an excellent non-invasive tool for diagnosing cardiac malformations in Down syndrome.     

Localised intravascular coagulation complicating venous malformations in children: Associations and therapeutic options

Venous malformations are slow‐flow congenital vascular malformations that enlarge as the child ages and may be associated with localised intravascular coagulation, a consumptive coagulopathy characterised by elevated D‐dimer and decreased fibrinogen levels. The authors review the known correlations between localised intravascular coagulation and venous malformation number, size and planes involved, and call attention to the concept of the progression of localised intravascular coagulopathy as the child ages and their venous malformations enlarge. The authors also discuss the identified therapeutic options for its investigation, management and treatment, including compression garments, anti‐coagulation therapy, sclerotherapy, endovascular laser, surgical excision and sirolimus (rapamycin). Evidence for protocol improvements that may be instigated for the optimal physical and medical therapy of venous malformations complicated by localised intravascular coagulopathy is reviewed.     

Down Syndrome as a Factor Influencing Hemodynamic Response to Pulmonary Artery Banding

The hemodynamic response to pulmonary artery banding (PAB) in relation to the preoperative pulmonary/systemic vascular resistance (R_p/R_s) ratio and to the timing of surgery, with special regard to Down syndrome, was investigated in 56 nonconsecutive pediatric patients aged 3 days to 6 months (mean 2.5 months) with simple and complex congenital shunt-related cardiac malformations. Among the non-Down patient group (39 patients; mean age 6.9 weeks) there was a good hemodynamic response in all but three cases, irrespective of the preoperative R_p/R_s ratio; these three poor responders had preoperatively normal or nearly normal R_p/R_s ratios (R_p/R_s < 0.3) and were affected postoperatively by lung complications. In the Down patient group (17 patients; mean age 8.2 weeks) the mean preoperative as well as the mean postoperative R_p/R_s ratio was higher than in the non-Down patient group (preoperative R_p/R_s 0.49 versus 0.32; postoperative R_p/R_s 0.31 versus 0.18). There was a good hemodynamic response in all five patients with Down syndrome who had preoperative normal or nearly normal pulmonary vascular resistance ratios (R_p/R_s < 0.3). Among 12 patients with Down syndrome and preoperative increased resistance ratios (R_p/R_s > 0.3) PAB did not cause a reduction in pulmonary vascular resistance (PVR) in five patients (postoperative R_p/R_s 0.49–1.00), all operated on at more than 6 weeks of age. PAB resulted in effective reduction of postoperative R_p/R_s ratios (range 0.10–0.27) in seven patients, six of them younger and one older than 6 weeks at the time of the banding procedure. In conclusion, patients with Down syndrome and shunt-related cardiac malformations (predominantly total atrioventricular canal cases) in general have higher pre- and postoperative R_p/R_s ratios than non-Down children and also have a higher potential for developing pulmonary vascular obstructive disease despite hemodynamically effective PAB. Especially in children with Down syndrome and pathologically high resistance ratios, PAB, if indicated, should be performed as early as possible.     

Gastrointestinal Malformations Associated with Prune Belly Syndrome: Three Cases and a Review of the Literature

Prune belly syndrome (PBS), a triad consisting of abdominal musculature hypoplasia, urinary tract malformations, and cryptorchidism, is frequently associated with other congenital malformations. Although it is acknowledged that gastrointestinal (GI) malrotation and mesenteric anomalies are frequent in PBS, other GI anomalies are generally considered to be exceedingly rare. Here we describe 3 autopsy cases with severe malformations of both midgut and hindgut derivatives and review the world literature to evaluate the spectrum of GI malformations associated with this syndrome. The relatively high frequency of distal stenoses and atrcsias suggests that the anomalous mesenteric attachments may predispose to prenatal volvulus and subsequent anatomic bowel obstruction. Postnatal volvulus is also occasionally observed. Infants with PBS also appear to be at a higher risk for persistence of the common fetal cloaca.     

Gastrointestinal malformations associated with prune belly syndrome: three cases and a review of the literature

Prune belly syndrome (PBS), a triad consisting of abdominal musculature hypoplasia, urinary tract malformations, and cryptorchidism, is frequently associated with other congenital malformations. Although it is acknowledged that gastrointestinal (GI) malrotation and mesenteric anomalies are frequent in PBS, other GI anomalies are generally considered to be exceedingly rare. Here we describe 3 autopsy cases with severe malformations of both midgut and hindgut derivatives and review the world literature to evaluate the spectrum of GI malformations associated with this syndrome. The relatively high frequency of distal stenoses and atresias suggests that the anomalous mesenteric attachments may predispose to prenatal volvulus and subsequent anatomic bowel obstruction. Postnatal volvulus is also occasionally observed. Infants with PBS also appear to be at a higher risk for persistence of the common fetal cloaca.     

A new approach to blue rubber bleb nevus syndrome: the role of capsule endoscopy and intra-operative enteroscopy

Blue rubber bleb nevus syndrome (BRBNS) is a rare vascular malformation disorder with cutaneous and visceral lesions frequently associated with serious, even fatal bleeding and anemia. The syndrome is considered to be autosomaly predominantly inherited. Intra-operative enteroscopy (IOE) is the best method of identification of all lesions (particularly the small ones, less than 3 mm) and treatment by endoscopic electro-coagulation or surgical excision. Capsule wireless endoscopy is optimal for screening before the IOE and for monitoring the effect of therapy (in patients with BRBNS). We report two cases of BRBNS. Anemia, gastrointestinal bleeding, gastrointestinal malformations and multifocal venous malformations of the skin were present in both of our cases. Gastrointestinal lesions were identified by gastroscopy, colonoscopy and capsule endoscopy. The multiple venous malformations were treated partly by endoscopic electro-coagulation (lesions up to 4 mm in diameter) and by wedge resection. Both of our patients were 12-year-old girls at the time of operation. In the first patient 31 venous malformations of the small bowel were coagulated, two were resected by the surgeon. In the second patient 20 lesions were coagulated endoscopically and another 31 nevi were resected during an 8 h procedure. The first girl is doing fine 4 years after the procedure, the second was allowed home 2 weeks after the procedure in excellent condition. IOE is a unique method of small bowel investigation and concurrently provides a solution for pathological findings. Capsule endoscopy is a feasible non-invasive screening procedure. We believe that a radical eliminatory approach by means of combined surgery and IOE is indicated for the BRBNS to prevent ongoing gastrointestinal bleeding.     

Acute mesenteroaxial gastric volvulus and congenital diaphragmatic hernia

The current report describes the case of an 11-year-old girl with Down syndrome who was admitted because of sudden abdominal pain and vomiting. Her symptoms were secondary to severe gastric volvulus associated with congenital diaphragmatic hernia.