Israel Medical Association Journal

Background: Granulocyte colony-stimulating factor has had a major impact on the management of severe chronic neutropenia – a collective term referring to congenital, idiopathic, or cyclic neutropenia. Almost all patients respond to G-CSF[1] with increased neutrophils, reduced infections, and improved survival. Some responders with congenital neutropenia (termed Kostmann’s syndrome herein) and Shwachman-Diamond syndrome have developed myelodysplastic syndrome and acute myeloid leukemia, which raises the question of the role of G-CSF in pathogenesis. The issue is complicated because both disorders have a propensity for MDS[2] or AML[3] as part of their natural history.

Objective and Methods: To address this, the Severe Chronic Neutropenia International Registry used its large database of chronic neutropenia patients treated with G-CSF to determine the incidence of malignant myeloid transformation in the two disorders, and its relationship to treatment and to other patient characteristics.

Results: As of January 2001, of the 383 patients with congenital forms of neutropenia in the Registry, 48 had MDS or AML (crude rate, about 12.5%). No statistically significant relationships were found between age at onset of MDS or AML and patient gender, G-CSF dose, or duration of G-CSF therapy. What was observed, however, was the multistep acquisition of aberrant cellular genetic changes in marrow cells from Kostmann’s syndrome patients who transformed, including activating ras oncogene mutations, clonal cytogenetic abnormalities, and G-CSF receptor mutations. The latter in murine models produces a hyperproliferative response to G-CSF, confers resistance to apoptosis, and enhances cell survival.

Conclusions: Since Kostmann’s syndrome and Shwachman-Diamond syndrome are inherited forms of bone marrow failure, G-CSF may accelerate the propensity for MDS/AML in the genetically altered stem and progenitor cells, especially in those with G-CSF receptor and ras mutations (82% and 50% of Kostmann’s syndrome patients who transform, respectively). Alternatively, and equally plausible, G-CSF may simply be an innocent bystander that corrects neutropenia, prolongs patient survival, and allows time for the malignant predisposition to declare itself. Only careful long-term follow-up of the cohort of patients receiving G-CSF will provide the answer.

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[1] G-CSF = granulocyte colony-stimulating factor

[2] MDS = myelodysplastic syndrome

[3] AML = acute myeloid leukemia

Recent data have shed significant new light on the structural and functional development of the kidneys, as well as on a rare congenital form of bilateral renal hypoplasia called congenital oligomeganephronia. In this renal disorder, few greatly enlarged and hard-working nephrons are found that will ultimately sclerose and lead to end-stage renal failure during early childhood. At the same time it has been recognized that the number of nephrons in the kidneys of various animal species and humans is correlated to renal mass. Therefore, premature babies and/or infants small for gestational age due to intrauterine malnutrition will be born with relatively small kidneys and a certain nephron deficit, a condition called congenital oligonephropathy. Extensive worldwide epidemiologic studies have now shown that these premature or SGA[1] infants have a high incidence of cardiovascular disease, hypertension, hyperlipidemia, diabetes and renal failure in adulthood. Although the pathophysiologic mechanisms responsible for these complications of premature birth are not entirely understood, it has become clear that the described association may pose a possible health problem in the adult population. This review describes the background of COMN[2] and CON[3] as well as the evidence that has accumulated on the adult complications of the latter. In addition, some thoughts are presented on the importance of identifying subjects possibly affected by CON, such that early recognition may alter the ultimate outcome.

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Background: Routine prenatal ultrasound has increased the frequency of prenatal diagnosis of congenital cystic lung malformation, such as cystic adenomatoid malformation, pulmonary sequestration, congenital lobar emphysema, and bronchogenic cyst.

Objectives: To evaluate the methods of postnatal diag­nosis, the optimal age for operation since surgery is always required, and the optimal extent of lung resection.

Methods: The clinical courses of 11 patients with congenital lung cysts who underwent surgical lung resection (8 lobectomies and 3 segmentectomies) were reviewed.

Results: The diagnosis was confirmed by computed tomography scan in all. In nine patients the diagnosis was made prenatally. Chest X-ray was normal postnatally in all patients except for two who had recurrent pneumonia. Post­operative follow-up showed excellent recovery in all operated children. One patient who underwent surgery for CCAM following episodes of severe pneumonia died from another cause 5 months later. Postoperative chest CT scan showed no residual disease in eight patients. In two who had undergone limited resection, tomography showed a small segment of residual disease in one and a suspected residual lesion in the other.

Conclusion: With prenatal ultrasound the true frequency of congenital cystic lung anomaly appears to be higher than previously reported. Postnatal CT is mandatory to confirm or to rule out the diagnosis. The mere presence of cystic lung malformation is an indication for surgery. Complete removal of the affected lung lobe is recommended. Segmental resection may be inadequate. Early operation is tolerated well by infants and small children and we recommend that surgery be performed in children between 6 and 12 months of age.

Background: Congenital subependymal pseudocysts are incidental findings that are found in 05-5.2% of neonates during postmortem examination or head ultrasonography. In our institution we detected 10 neonates with CSEPC.

Objective: To investigate associated etiological factors, morphologic characteristics and outcome of CSEPC.

Methods: We performed a meta-analysis of the literature on CSEPC (1967-98), including our 10 cases.

Results: A total of 256 cases of CSEPC were analyzed. Ultrasound diagnosed 77.6% of CSEPC 48.8% were bilateral and 53.4% were located in the caudothalamic groove or head of caudate nucleus. Altogether, 93.5% resolved during 1-12 months of ultrasonographic follow-up. Compared to the general neonatal population, the following features were more prevalent in the CSEPC population: prematurity, maternal vaginal bleeding, preeclamptic toxemia, intrauterine growth restriction, asphyxia, fetal cytomegalovirus and rubella infec­tions, congenital malformations, chromosomal aberrations, infant mortality, and neurodevelopmental handicap. The risk for neurodevelopmental handicap was significantly higher when CSEPC were associated with fetal infections, IUGR, malformations and chromosomal aberrations, or persistence of CSEPC during follow-up. CSEPC infants without any of these four conditions had a low risk for neurodevelopmental handi­cap.

Conclusions: CSEPC are morphologic features of various underlying conditions encountered in the fetus. Association of CSEPC with IUGR, fetal infections, malformations and chromosomal aberrations or persistence of CSEPC indicates a higher risk for future neurodevelopmental handicaps, probably because of the deleterious effects on the fetal brain that are inherent in these conditions. A favorable outcome is expected in the absence of these risk factors.
 

Background: Parental knowledge of their child’s heart disease, while often overlooked, contributes to compliance and reduces anxiety. Prior studies have shown that 36% of parental diagnostic descriptions are incorrect.

Objectives: To assess parental knowledge and attitudes among outpatients at a hospital pediatric cardiology clinic.

Methods: Seventy-four families completed a questionnaire in which they described their child’s condition and stated their attitude towards dental hygiene and future prenatal diagnosis.

Results: Eighteen percent of the parents failed to describe their child’s malformation correctly. We found that parental understanding of the heart defect correlated with parental education. Future prenatal diagnosis was considered by 88% of families, and termination of pregnancy by 40%. Only 40% of children were aware of their heart problem. Children of parents who were ignorant about the condition tended to lack knowl­edge themselves. An additional finding was that 68% of Jewish families turn to non-medical personnel for medical advice - an interesting finding not hitherto addressed.

Conclusions: Ignorance of their child’s problem did not correlate with its severity or complexity but rather with parental background: the less educated the parent, the more likely was the problem perceived incorrectly.
 

Background: Secundum atrial septal defect is a common congenital heart defect that causes right heart volume overload and produces symptoms usually after the third decade of life. Treatment until the last few years has been open heart surgery.

Objective: To review our early experience with transcatheter closure of ASD2 using the Amplatzer septal occluder.

Methods: Between November 1999 and February 2000, 20 children and young adults with a median age of 9.1 years (4.2-35.1 years) were referred for transcatheter closure of ASD2. Diagnosis was established by transthoracic echocardiography. Implantation was performed under general anesthesia through the femoral vein with the guidance of transesophageal echocardiography and fluoroscopy. Femoral arterial puncture was performed for blood pressure monitoring during the procedure. The device size chosen was similar to the balloon-stretched diameter of the ASD2.

Results: Implantation was completed successfully in 18 patients. Two patients were referred for elective surgery: one had an unsuitable anatomy for transcatheter closure by TEE in the catheterization laboratory and the device could not implanted properly, the other patient had a large multiperforated septal aneurysm that was retrieved. Mean ASD2 diameter by TTE and TEE was similar (13.9 + 3 mm, 13.4 + 3.5 mm) and mean stretched diameter was 18.3 + 4.3 mm. Mean Qp:Qs (pulmonary flow: systemic flow) was 2.2 + 0.6. Mean fluoroscopy time for the procedure was 14.8 + 4.8 minutes.

The patients were discharged the day after the procedure.

Four patients had a tiny leak immediately post-procedure, and none had a leak at one month follow-up. The only complication was a small pseudoaneurysm of the femoral artery in one patient, that resolved spontaneously.

Conclusion: Transcatheter closure of ASD2 with the Amplatzer septal occluder is a safe and effective alternative to surgical closure. Long-term outcome has to be evaluated.

Background: A high rate of consanguineous marriages exists within the Israeli Arab community, with approximately half occurring between first cousins. This contributes towards a high incidence of congenital malformations and autosomal recessive diseases, many of which are detectable at prenatal diagnosis.

Objectives: To assess the levels of both awareness and acceptance regarding prenatal diagnosis and termination of pregnancy among a group of Arab women in order to devise the optimal means of providing genetic counseling and general health services.

Methods: A total of 231 Arab women of childbearing age were interviewed 3 days postpartum to assess their knowledge of prenatal diagnosis and termination of pregnancy, their willingness to undergo prenatal diagnosis, and their opinions on termination of pregnancy in the event of a severely affected fetus.

Results: Half the women believed that prenatal testing is not an effective (or accurate) tool for diagnosing an affected fetus. A quarter had poor knowledge on prenatal diagnosis, and a quarter believed that prenatal diagnosis does provide the correct diagnosis. Ninety-five percent said they would agree to undergo prenatal diagnosis; and in the event of a severely affected fetus, 36% said they would agree to a termination of pregnancy, 57% said they would not, and 7% were undecided.

Conclusions: There is a need for special intervention programs, with guidance by health professionals, geneticists and religious authorities, that will inform this population on the increased risk associated with consanguinity, stress the importance and effectiveness of prenatal testing to identify severe congenital malformations, and help them to accept prenatal diagnosis and termination of pregnancy if indicated.

Objective: To review the clinical presentation of gastrointestinal duplications and present our experience with such lesions over the past decade.

Methods: The records of all patients treated for gastrointestinal duplications at a tertiary hospital during 1987 through 1996 were collected, and relevant published literature reviewed.

Results: In the nine patients with gastrointestinal duplications, six were in the small bowel and one each in the cecum, colon and esophagus. Presenting clinical features were varied and often subtle. Perinatal ultrasonography, radioscintography and computerized tomography were useful in some cases, while in others the correct diagnosis was established only at surgery.

Conclusions: Alimentary tract duplications are uncommon, and may present as solid or cystic tumors, intussusception, perforation or gastrointestinal bleeding. A high index of suspicion is required when dealing with such cases. Appropriate investigations, including imaging techniques, should be directed toward adequate and planned surgery.