Velocardiofacial syndrome: incidence of immune cytopenias.

BACKGROUND: Velocardiofacial syndrome (VCFS) is associated with a broad clinical spectrum that frequently overlaps the DiGeorge syndrome. Both have been linked to chromosomal microdeletions of chromosome 22 (22q11.2). DiGeorge syndrome is associated with T-cell dysfunction. What is the incidence of immune cytopenias in children with VCFS? OBJECTIVES: To (1) identify, (2) characterize, (3) quantify, and (4) follow up the immunologic deficits in children initially seen in our institution with VCFS. DESIGN: Prospective clinical evaluation of patients with the features of VCFS. PATIENTS: Twenty consecutive children with the clinical diagnoses of VCFS. SETTING: Tertiary care children's hospital. MAIN OUTCOME MEASURES: All 20 children had genetics evaluation with chromosomal analysis. Immunologic evaluations included serum immunoglobulin concentrations, lymphocyte studies, and mitogen and antigen stimulation studies. RESULTS: Five (25%) of 20 children were noted to have T-cell dysfunction with a clinical presentation marked by recurrent upper respiratory tract infections. Three of these 5 children had resolution of the T-cell dysfunction over a 2-year period. The 2 children with persistent cytopenias combined with immunoglobulin dysfunction required intravenous IgG infusions to control their infections. CONCLUSIONS: Velocardiofacial syndrome is associated with an increased incidence of immune cytopenias and, thus, warrants evaluation in any child with the clinical diagnosis of VCFS. This immune deficit may be transient and depends on the age of the evaluation of the child.

Jumping translocation with partial duplications and triplications of chromosomes 7 and 15.

We report a 2-year-old female with seizures, mild dysmorphic features and a jumping translocation involving chromosome 15 that results in multiple cell lines with partial duplications and triplications of chromosomes 7 and 15. Fluorescent in situ hybridization (FISH) and chromosome microdissection were used to identify the complex nature of the jumping translocation. Interstitial telomeres were observed at the jumping translocation sites. The jumping chromosome rearrangement was also found to have a partial duplication of 7p as demonstrated by chromosome microdissection. Despite these partial duplications and triplications of chromosomes 7 and 15, the child does not have major birth defects. She does have mild sensorimotor delays. A review of non-Robertsonian jumping translocations is provided.

Prenatally diagnosed de novo apparently balanced complex chromosome rearrangements: two new cases and review of the literature.

Complex chromosome rearrangements (CCR) are rare structural rearrangements. Currently six cases of prenatally diagnosed balanced de novo CCR have been described. We present two new cases of prenatally ascertained balanced de novo CCR. In the first case, an amniocentesis revealed a balanced de novo three-way CCR involving chromosomes 5, 6, and 11 with a pericentric inversion of chromosome 5 [four breaks]. In the second case, a balanced de novo rearrangement was identified by amniocentesis which involved a reciprocal translocation between chromosomes 3 and 8 and a CCR involving chromosomes 6, 7, and 18 [six breaks]. The use of whole chromosome painting helped elucidate the nature of these rearrangements. A review of the postnatally ascertained cases suggests that most patients have congenital anomalies, minor anomalies, and/or developmental delay/mental retardation. In addition, there appears to be a relationship between the number of chromosome breaks and the extent of phenotypic effects. The paucity of information regarding prenatally diagnosed CCR and the bias of ascertainment of postnatal CCR cases poses a problem in counseling families.

Oculodental digital dysplasia: neuroimaging in a kindred.

Oculodental digital dysplasia (ODDD) is an uncommon inherited disorder with characteristic facial abnormalities, defects in dentition and syndactyly; previous reports have described neurologic dysfunction. We present neuroimaging features of a mother and daughter with ODDD; despite only the mother having neurologic dysfunction, the MRI findings in both are strikingly similar.

A mutation in FBN1 disrupts profibrillin processing and results in isolated skeletal features of the Marfan syndrome.

Dermal fibroblasts from a 13-yr-old boy with isolated skeletal features of the Marfan syndrome were used to study fibrillin synthesis and processing. Only one half of the secreted profibrillin was proteolytically processed to fibrillin outside the cell and deposited into the extracellular matrix. Electron microscopic examination of rotary shadowed microfibrils made by the proband's fibroblasts were indistinguishable from control cells. Sequencing of the FBN1 gene revealed a heterozygous C to T transition at nucleotide 8176 resulting in the substitution of a tryptophan for an arginine (R2726W), at a site immediately adjacent to a consensus sequence recognized by a cellular protease. Six other individuals in the proband's family had the FBN1 mutation that segregated with tall stature. None of the affected individuals have cardiac or ocular manifestations of the Marfan syndrome. This mutation identifies a putative site for profibrillin to fibrillin processing, and is associated with isolated skeletal features of the Marfan syndrome, indicating that the FBN1 gene is one of the genes that determines height in the general population. The cellular effect of the mutation may be equivalent to a "null" FBN1 allele and may define the phenotype associated with FBN1 "null" alleles.

Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) associated with interstitial deletion of band 3q22: review and gene assignment to the interface of band 3q22.3 and 3q23.

We report on a child with blepharophimosis, ptosis, and epicanthus inversus (BPES), developmental delay and an interstitial deletion of band q22 of chromosome 3. A review of chromosome 3q anomalies associated with eye abnormalities, specifically blepharophimosis and ptosis, strongly suggests that a locus for eyelid development is present at the interface of bands 3q22.3 and 3q23.

Najjar syndrome revisited.

We describe 2 brothers with cardiomyopathy and hypergonadotropic hypogonadism and conclude that this is the first description of the Najjar syndrome in the United States. The inheritance may be autosomal recessive.

Lethal bone dysplasia in a fetus with manifestations of atelosteogenesis I and Boomerang dysplasia.

Atelosteogenesis I (AT-I) and Boomerang dysplasia have been described as separate lethal bone dysplasias. The possibility of a common cause of both conditions was suggested by Hunter and Carpenter (Clin Genet 39(6): 471-480, 1991) in their report of a patient with apparent manifestations of both AT-I and Boomerang dysplasia. We report on a male fetus of 31 weeks gestation whose clinical, radiologic and histologic findings are compared to reported cases of AT-I, Boomerang dysplasia and the patient of Hunter and Carpenter (Clin Genet 39(6): 471-480, 1991). From the documentation of clinical and radiologic findings we demonstrate overlap of AT-I and Boomerang dysplasia in our patient, and, from histologic examination, suggest a defect of cartilage and bone formation as the basic abnormality in this lethal bone dysplasia.

Holzgreve syndrome: recurrence in sibs.

We report on 2 sibs with cardiac and renal abnormalities. The first had hypoplastic left heart sequence and renal hypoplasia; the second had a complex congenital heart defect, renal agenesis, and cleft lip and palate. We suggest that these cases represent the first familial examples of the Holzgreve syndrome. As such, they demonstrate the phenotypic variability seen in sibs, and may serve to further delineate the syndrome.

Comparative analysis of successful and unsuccessful candidates for the pediatric surgical matching program.

Only one third of the applicants for training in pediatric surgery obtain a position through the pediatric surgery matching program. In order to identify factors that contribute to a successful outcome, we conducted a retrospective survey of all participants in the matching process for positions during the years 1983 to 1991. This survey was designed to identify characteristics associated with success in the match through comparison of successful and unsuccessful applicants. Significant factors associated with a successful match included: a greater incidence of residency-supported research (P = .012) with a greater number of publications (P = .003) and national presentations (P = .014), specifically at the annual meetings of the American Pediatric Surgical Association (P = .05) and the American Academy of Pediatrics (P = .05). In addition, successful candidates had more contact with (P = .004) and letters of recommendation from (P = .015) well-known pediatric surgeons involved in the general surgical residency program. This information should be invaluable to those counseling medical students and residents interested in a career in pediatric surgery.

Familial Hirschsprung's disease: report of autosomal dominant and probable recessive X-linked kindreds.

Multifactorial sex-modified inheritance has been proposed as the model of transmission in familial Hirschsprung's disease (HD). A review of two separate kindreds suggests that aganglionosis may be inherited as an X-linked recessive or an autosomal dominant trait. Chromosomal anomalies and other syndromes, including G6PD deficiency, may occur with familial HD. Recurrence risk counseling for family members depends on accurate pedigree analysis and a comprehensive understanding of the genetic factors involved.

Prenatal cocaine exposure and fetal vascular disruption.

The question of the potential teratogenicity of cocaine has been raised by the increasing frequency of its abuse in the United States. In previous studies, an increased incidence has been documented of spontaneous abortion, placental abruption, prematurity, intrauterine growth retardation, and neurologic deficits in the infants of women who abused cocaine. More recently, it has been suggested in studies that fetal vascular disruption accompanying maternal cocaine abuse may lead to cavitary central nervous system lesions and genitourinary anomalies. In this article, 10 children born of women who abused cocaine are described, 9 of whom have congenital limb reduction defects and/or intestinal atresia or infarction. The spectrum of anomalies associated with embryonic and fetal vascular disruption accompanying maternal cocaine abuse is thus enlarged. The specific risk for congenital anomalies accompanying maternal cocaine abuse during an individual pregnancy is unknown. However, data from these patients and the available literature suggest that counseling pregnant women concerning cocaine use should incorporate warnings about the possibility of associated embryonic or fetal vascular disruption.

Colonic intussusception secondary to a calcium phosphate bezoar in a child receiving calcium carbonate for hyperphosphatemia.

We report a case of a calcium phosphate bezoar resulting in colonic intussusception in a boy with chronic renal failure who received calcium carbonate to control hyperphosphatemia. Because of concerns about aluminum-related disease in patients receiving aluminum hydroxide phosphate binders, calcium carbonate is being used more frequently to manage phosphate retention in renal failure. The development of bezoars may complicate this new form of therapy.

Immune consequences of nonoperative treatment of splenic trauma in the rat model.

To investigate the immunologic consequences of non-operative management of splenic injury, three parameters were studied: survival following pneumococcal sepsis, clearance of blood-borne bacteria, following Hemophilus influenzae challenge, and antibody response to type III pneumococcal capsular polysaccharide. Two hundred twenty-five Sprague-Dawley rats were divided into three groups and subjected either to a splenectomy, a sham operation, or standard blunt trauma. A significant increase in mortality was noted in the splenectomized group as compared with both the traumatized and control groups when challenged with Streptococcus pneumoniae. In both the control and trauma groups, H influenzae cleared significantly within 18 hours. Blood-borne bacteria persisted at the same level for 72 hours in the splenectomized animals. Four and 11 days later, the antibody level in both traumatized and control groups was higher than in the splenectomized subjects (P less than .001). There was no difference in the serum antibody level between the control and trauma groups at four days. However, at 11 days the trauma group showed a significant decrease in the antibody level (P less than .05). It can be concluded that following spontaneously-healing splenic trauma in the rat model, survival, bacterial clearance, and antibody response were all superior to that observed in the splenectomized subjects. In addition, the healed splenic disruption did not impair clearance of blood-borne encapsulated bacteria.

The role of pediatric surgery in the medical school curriculum.

In most medical schools, exposure to pediatric surgery is presented as a subspecialty elective. We have offered it as an integral part of the surgical clerkship for 10 years in the belief that it provides an excellent educational environment. To confirm this concept, the quizzes (Q), final examinations (FE), and grades of students assigned to the pediatric surgical service were prospectively studied. All students (N = 139) in the surgical clerkship entered the study. Thirty-two students were randomly selected and assigned to the surgical service of a major pediatric hospital (P-Surg) for 50% of their clerkship. The other students (N = 107) were assigned to a variety of adult surgical services (G-Surg) and served as the control group. All students attended the same seminars, used the same educational materials, were examined with the same test items, and were evaluated by the same oral examiners. Test items were electronically scored and the database was analyzed on an IBM computer. The statistical analysis was performed using a Student's t test and chi 2 analysis. There was no significant difference in the demonstrated cognitive performance and grades awarded to the two groups of students. We conclude that a pediatric surgical service provides an atmosphere that is educationally comparable to the adult general surgical service.

Omphalocele with pyloroduodenal obstruction by extrinsic hepatic compression: a case report.

The diagnosis of gastroduodenal obstruction by hepatic compression following omphalocele closure must be suspected in the presence of persistent nonbilious vomiting. We feel that computed tomography (CT) is the appropriate imaging method to define the liver abnormality. Nonsurgical management is the best approach with nutritional support maintained by total parenteral nutrition until physiological resolution of the obstruction occurs.