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Objective: We present prenatal diagnosis of Jacobsen syndrome associated with a distal 11q deletion and a distal 8q duplication by chromosome microarray analysis (CMA) in a fetus with multiple congenital anomalies on fetal ultrasound. Case Report: A 41-year-old, gravida 2, para 1, woman underwent amniocentesis at 25 weeks of gestation because of intrauterine growth restriction, endocardial cushion defect, clenched hands, arthrogryposis, rocker bottom feet and craniosynostosis on fetal ultrasound. Amniocentesis revealed a karyotype of 46,XX,add(11)(q23.3). Array comparative genomic hybridization (aCGH) analysis of the DNA extracted from the uncultured amniocytes revealed the result of arr 8q24.13q24.3 × 3, 11q23.3q25 × 1. Analysis of FGFR2 revealed no mutation. The karyotype was 46,XX,der(11)t(8;11)(q24.13;q23.3). The parental karyotypes were normal. The pregnancy was subsequently terminated, and a dead malformed fetus was delivered with craniofacial dysmorphism of low-set malformed ears, depressed nasal bridge, hypertelorism, small mouth, clenched hands and rocker bottom feet. Cytogenetic analysis of the placenta revealed a karyotype of 46,XX,der(11)t(8;11)(q24.13;q23.3). aCGH analysis of the DNA extracted from the umbilical cord showed the result of arr 8q24.13q24.3 (126,302,369–146,280,020) × 3.0, arr 11q23.3q25 (120,469,928–134,868,407) × 1.0 [GRCh37] with a 19.978-Mb duplication of 8q24.13-q24.3 and a 14.398-Mb deletion of 11q23.3-q25 encompassing the genes of BSX, ETS1, FLI1 and ARHGAP32. Conclusion: CMA is useful for detection of de novo chromosomal rearrangement in the fetus with multiple congenital anomalies on fetal ultrasound.

Introduction. Jacobsen syndrome (JS) is a rare genetic disease associated with the deletion of chromosome 11q, characterized by multiple malformations, hematological and immune disorders. The development of immunodeficiency in JS is often underestimated, which leads to recurrent infectious complications. Presentation of a clinical case. The article presents a clinical case of a patient with a deletion of chromosome 11q and combined immunodeficiency. Our patient had recurrent infections, cytopenic syndrome, combined immunodeficiency, as well as other clinical manifestations of Jacobsen syndrome. In addition to a decrease in serum immunoglobulins, a deep deficiency of the T-cell link of immunity with a low content of T-lymphocytes, recent emigrants from the thymus, has been established. Conclusions. The peculiarity of the presented clinical case is that with a relatively small amount of deletion 11q, the child realized a complete clinical phenotype of the disease and a deep combined immunodeficiency. The article was written to improve doctors’ knowledge about this rare form of congenital immunodeficiency.

The article presents a literature review of chromosomal deletion syndrome – terminal deletion of the long arm of chromosome 11, Jacobsen syndrome, manifested by skeletal abnormalities, congenital heart defects, developmental delay, autism. The disease is of clinical interest in connection with a specific phenotype and life-threatening, but potentially curable conditions: bleeding and immunodeficiency. The analysis of informationally significant genes of the chromosome 11 deletion site is presented. A case report of a girl with Jacobsen syndrome with a follow-up history of up to 6 years is presented. In the observed case, previously unremarked symptoms were described: ataxia and retropulsion. The differential diagnosis and criteria for hypomyelination syndrome are also analyzed. Recommendations are given for the management of life-threatening conditions in patients in accordance with American protocols.

Key Clinical Message Recurrent severe respiratory infections in Jacobsen syndrome (JS) are unusual and should prompt evaluation of the immune system. A variety of immune defects have been reported in JS and intravenous immune globulin (IVIG) treatment reduces severe infections.

Abstract Background Jacobsen syndrome is a rare genetic disorder with multiple congenital anomalies and platelet abnormalities caused by chromosome 11 deletion. Case presentation A 7-month-old boy with thrombocytopenia underwent ventricular septal defect closure. At the beginning of surgery, the platelet count was 168 × 103/μL, and heparinized kaolin with heparinase reaction time (HKH-R), which represents clot formation time, was prolonged at 30.4 min. Platelet transfusion was continued, and at the end of surgery, the platelet count and HKH-R values improved to 215 × 103/μL and 15 min, respectively. Conclusions As anesthetic management of patients with abnormal platelet function, the viscoelasticity test might be useful in evaluating hemostatic capacity.

Jacobsen syndrome is a rare genetic disorder associated with a terminal deletion in chromosome 11. The clinical presentation is variable. Although immunodeficiency has been described in patients with Jacobsen syndrome, a clear genotype-phenotype correlation has not yet been established. Here, we report on the immunologic phenotypes of four patients with Jacobsen syndrome. All four patients showed one or more atypical immunologic features. One patient suffered from recurrent viral infections, two patients had experienced a severe bacterial infection and one had received antibiotic prophylaxis since early childhood. One patient had experienced severe, transient immune dysregulation. Hypogammaglobulinemia and low B cell counts were found in two patients, while the number of recent thymic emigrants (CD31+CD45RA+ CD4 cells) was abnormally low in three. When considering the six immune-related genes located within the affected part of chromosome 11 (ETS1, TIRAP, FLI1, NFRKB, THYN1, and SNX19), only the ETS1 gene was found be deleted in the three patients with low numbers of recent thymic emigrants and non-switched memory B cells. Our findings support the hypothesis whereby Jacobsen syndrome is associated with a combined immunodeficiency with variable presentation. Further investigations of potential genotype-phenotype correlations are warranted and might help to personalize patient management in individuals lacking immune-related genes. In addition, we recommend immunologic follow-up for all patients with Jacobsen syndrome, as immune abnormalities may develop over time.

Jacobsen syndrome (JS) is a rare syndrome caused by a deletion of chromosome 11q. We report a patient with JS and hypoplastic left heart syndrome (HLHS) who required cardiac transplantation. She had many of the recognized morphological features in addition to immunological (lymphopenia) and hematological (thrombocytopenia) issues. The patient underwent a Norwood procedure with a modified Blalock–Taussig shunt (MBTS) and subsequently a Glenn procedure at six months of age. She developed desaturation, with severe tricuspid regurgitation and right ventricular dysfunction, and underwent heart transplantation at 7 months of age. After the transplant, she was hospitalized several times for severe infections. The diagnosis of Jacobsen syndrome came 2 months after transplant. Now, 5 years post-transplant, she is in relatively good health—her heart is functioning normally, her hospitalization rate is getting lower, and her immunological profile is stable.

We have identified the ETS1 gene as the cause of congenital heart defects, including an unprecedented high frequency of HLHS, in the chromosomal disorder Jacobsen syndrome. Studies in Ciona intestinalis demonstrated a critical role for ETS1 in heart cell fate determination and cell migration, suggesting that the impairment of one or both processes can underlie the pathogenesis of HLHS. Our studies determined that ETS1 is expressed in the cardiac neural crest and endocardium in the developing murine heart, implicating one or both lineages in the development of HLHS. Studies in Drosophila and Xenopus demonstrated a critical role for ETS1 in regulating cardiac cell fate determination, and results in Xenopus provided further evidence for the role of the endocardium in the evolution of the “hypoplastic” HLHS LV. Paradoxically, these studies suggest that the loss of ETS1 may cause a cell fate switch resulting in the loss of endocardial cells and a relative abundance of cardiac myocytes. These studies implicate an “HLHS transcriptional network” of genes conserved across species that are essential for early heart development. Finally, the evidence suggests that in a subset of HLHS patients, the HLHS LV cardiac myocytes are, intrinsically, developmentally and functionally normal, which has important implications for potential future therapies.

Abstract Background 11q23 deletion syndrome, also known as Jacobsen syndrome, is characterized by growth retardation, psychomotor retardation, facial dysmorphism, multiple congenital abnormalities, and thrombocytopenia. In 11q23 deletion syndrome, it is often difficult to anticipate the severity of bleeding. We report a neonatal case of 11q23 deletion syndrome with bleeding that was more severe than predicted by the platelet count. Case presentation We report a case of 11q23 deletion syndrome in an Asian male newborn with severe bleeding just after birth. The diagnosis of 11q23 deletion syndrome was made prenatally by amniocentesis. An array comparative genomic hybridization analysis revealed a deletion of the 13.0 Mb regions ranging from 11q24.1 to the q terminus encoding FLI1. Our patient was delivered by cesarean section and exhibited skull deformities, facial asymmetry, low-set ears, inguinal hernia, flat feet, and crowded toes. He had a low platelet count (45,000/μL) and a coagulation abnormality with a prothrombin time–international normalized ratio of 1.92 and an activated partial thromboplastin time of 158.6 seconds. Bleeding at the site of a peripheral vessel puncture was more severe than expected with thrombocytopenia. The peripheral blood featured two different sizes of platelets containing large α-granules. As a result, he required eight platelet transfusions and two fresh frozen plasma transfusions within 13 days of birth. Massive bleeding was avoided, and cerebral magnetic resonance imaging indicated the occurrence of only petechial hemorrhage. Conclusions Our patient with 11q deletion including FLI1 avoided massive bleeding and serious sequelae because of careful management after prenatal diagnosis. We suggest that prenatal diagnosis and vigilant perinatal care including a cesarean section are warranted for patients with 11q23 deletion syndrome.

Objective: We present molecular cytogenetic characterization of Jacobsen syndrome (11q23.3-q25 deletion) in a fetus associated with double outlet right ventricle (DORV), hypoplastic left heart syndrome (HLHS), and ductus venosus (DV) agenesis on prenatal ultrasound. Case Report: A 26-year-old woman underwent prenatal ultrasound examination at 22 weeks of gestation, which revealed intrauterine growth restriction, short femurs, DORV, HLHS, DV agenesis, single umbilical artery, and curly fourth toe of the left foot. The parents elected to terminate the pregnancy, and a 500-g female fetus was delivered at 23 weeks of gestation with facial dysmorphism, bilateral camptodactyly, and hammertoes. The parental karyotypes were normal. Cytogenetic analysis of the cord blood and umbilical cord revealed a karyotype of 46,XX,del(11)(q23). Array comparative genomic hybridization analysis of the DNA extracted from the umbilical cord revealed a 14.38-Mb deletion of 11q23.3-q25 encompassing BSX, ETS1, FLI1, and ARHGAP32. Metaphase fluorescence in situ hybridization analysis using the probes RP11-209L12 (11q25) and RP11-25M7 (11q11) showed a distal 11q deletion in the aberrant chromosome 11 in 17/17 cells examined. Conclusion: Prenatal diagnosis of DORV, HLHS, DV agenesis associated with intrauterine growth restriction and short limbs should include a differential diagnosis of Jacobsen syndrome.

Hypoplastic left heart syndrome occurs in up to 3% of all infants born with congenital heart disease and is a leading cause of death in this population. Although there is strong evidence for a genetic component, a specific genetic cause is only known in a small subset of patients, consistent with a multifactorial etiology for the syndrome. There is controversy surrounding the mechanisms underlying the syndrome, which is likely due, in part, to the phenotypic variability of the disease. The most commonly held view is that the “decreased„ growth of the left ventricle is due to a decreased flow during a critical period of ventricular development. Research has also been hindered by what has been, up until now, a lack of genetically engineered animal models that faithfully reproduce the human disease. There is a growing body of evidence, nonetheless, indicating that the hypoplasia of the left ventricle is due to a primary defect in ventricular development. In this review, we discuss the evidence demonstrating that, at least for a subset of cases, the chamber hypoplasia is the consequence of hyperplasia of the contained cardiomyocytes. In this regard, hypoplastic left heart syndrome could be viewed as a neonatal form of cardiomyopathy. We also discuss the role of the endocardium in the development of the ventricular hypoplasia, which may provide a mechanistic basis for how impaired flow to the developing ventricle leads to the anatomical changes seen in the syndrome.

Background. Jacobsen syndrome is a rare syndrome with variable phenotypic expression depending on the breakpoints and the size of 11q deletion. There is presented a wide range of phenotypes of varying severity. Detailed molecular cytogenetic analysis leads to better knowledge of genetic causes of this syndrome. Materials and methods. Molecular cytogenetic analysis using subtelomeric FISH and array CGH was performed for a patient with Jacobsen syndrome. Results. Subtelomeric FISH detected an unbalanced translocation 46,XY,der(11)t(11;13)(q24.2;p11.2) of our patient. Array CGH analysis revealed a 13.95 Mb terminal deletion of the 11q23.3 region (breakpoint positions 120, 505, 418–134, 452, 384, NCBI build 36). FISH and GTG banding analysis identified a balanced translocation 46,XX,t(11;13) (q24.2;p11.2) of patient’s mother. Conclusions. The results of this case report suggest the need of combining both molecular cytogenetic methods: array CGH and FISH for precise analysis of patients with Jacobsen syndrome.