11q23 deletion syndrome (Jacobsen syndrome) with severe bleeding: a case report

A contiguous gene syndrome, 11q23 deletion syndrome is characterized by growth retardation, psychomotor retardation, facial dysmorphism, multiple congenital abnormalities, abnormal platelet function, and thrombocytopenia. The syndrome is also known as Jacobsen syndrome and the congenital thrombocytopenia/thrombocytopathy observed in most of the affected patients is considered to be the same as that in Paris-Trousseau syndrome [1]. Thrombocytopenia in patients with 11q23 deletion syndrome was determined to be associated with the hemizygous loss of the friend leukemia integration 1 transcription factor (FLI1), which is located in the 11q23 chromosome band and appears to be involved in early hematopoietic, megakaryopoietic, and vascular development [2, 3]. In patients with 11q23 deletion syndrome, the platelet count decreases to less than 50,000/μL and bleeding occurs to varying degrees of severity. Platelet abnormality is highly penetrant in 11q23 deletion syndrome, affecting at least 88.5% of patients with the condition [1]. However, it is difficult to predict the severity of bleeding by prenatal diagnosis or platelet count. Therefore, this factor can interfere with qualified perinatal care and may cause life-threatening events leading to an undesirable sequela. We report here a neonatal case of 11q23 deletion syndrome with bleeding that was more severe than predicted by the platelet count. We avoided massive bleeding and serious sequelae by careful management after prenatal diagnosis.

A 39-year-old gravida 1 para 1 woman was referred for amniocentesis due to intrauterine growth retardation at 27 gestational weeks. Distal abnormality of chromosome 11: 46,XY, del (q23 > qter) was found. At 36 weeks’ gestation, she went into labor. An Asian male newborn weighing 1082 g with an Apgar score of 5 and 8 at 1 and 5 minutes, respectively, was delivered by cesarean section because of oligohydramnios and a non-reassuring fetal status. In the first hour of life, he developed respiratory failure and was placed on a ventilator. His white blood and red blood cell counts were within the normal range although his platelet count was 45,000/μL with an accompanying coagulation abnormality as indicated by a prothrombin time–international normalized ratio of 1.92 and an activated partial thromboplastin time of 158.6 seconds. He exhibited dolichocephaly with high prominent forehead, facial asymmetry, low-set ears, inguinal hernia, flat feet, and crowded toes. An echocardiogram confirmed hydronephrosis. On capillary blood sampling, bleeding at the site of the peripheral vessel puncture was very severe and required 2 or more hours of oxidized cellulose hemostatic treatment for hemostasis to occur. Since bleeding symptoms were more severe than the thrombocytopenia, he was sedated to avoid intracranial bleeding. Platelets were heterogeneous in size and α-granule morphology was observed in the peripheral blood smears. Some platelets contained giant α-granules that decreased in number (Fig. 1). His platelet count decreased to 18,000/μL on day 6. He required eight platelet transfusions to keep the platelet count above 30,000/μL as well as two transfusions of fresh frozen plasma during the first 13 days after birth to prevent extensive bleeding. He required ventilation until day 11, continuous positive airway pressure until day 54, and oxygenation until day 67. He appeared to have difficulty with oral feeding, but was able to gain the appropriate amount of weight by tube feeding. He was discharged on day 88. At this time, brain magnetic resonance imaging indicated a petechial hemorrhage, which is often seen in neonates, but no hematoma. His platelet count increased to 50,000 to 80,000/μL with normal coagulation although the bleeding time remained prolonged at 6 minutes. An array comparative genomic hybridization analysis confirmed deletion of the 13.0 Mb regions ranging from 11q24.1 to the q terminus encoding FLI1, BSX, and BARX2 (Fig. 2).