Cerebral Palsy

Jumping translocations (JTs) are rare constitutional or acquired rearrangements involving a donor and several receiver chromosomes. They may be inherited or de novo. JTs can be found as a cultural artifact, in normal individuals or in pathological conditions. The clinical consequences range from spontaneous abortion, loss of fetus, chromosome syndrome, congenital abnormalities, and infertility to malignancy. Considering the breakpoints of JTs, they are localized predominantly in repeat regions such as pericentromeric, centromeric, subtelomeric, telomeric, and occasionally interstitial regions that may be in a low copy repeats (LCR) or in a telomere like sequence. Differences between the constitutional and acquired JTs donor breakpoints suggest an independent mechanism in their formation. In this review, a new JT involving a donor chromosome 18p10qter and recipients 17q25qter or 1q25qter found by CVS of a twin pregnancy is described. This case illustrates the diagnostic challenges posed by JTs.In this study, our knowledge on JTs is consolidated to improve identification, management, and counseling. © 2010 Wiley-Liss, Inc.

We present a 20-year follow-up on a patient with a ring chromosome 14. The ring chromosome was studied by fluorescence in-situ hybridization (FISH), multiplex-ligation probe amplification (MLPA), and genome wide SNP array, and no deletions of chromosome 14 were detected, although the telomeric repeat sequence was absent from the ring chromosome. The patient had skeletal abnormalities, and susceptibility to infections, as well as seizures and retinal pigmentation, which are commonly found in individuals with a ring 14. Our patient corroborates the idea that even when no genes are lost during ring formation, a complete ring chromosome can produce phenotypic alterations, which presumably result from ring instability or gene silencing due to the new chromosomal architecture. © 2010 Wiley-Liss, Inc.

Costello syndrome is a rare developmental disorder characterized by coarse face, postnatal growth retardation, skin and musculoskeletal anomalies, cardiovascular abnormalities, mental retardation, and tumor predisposition. Dermatological manifestations usually include redundant, soft and thickened skin. Loose skin is especially present over the neck, hands, and feet. Heterozygous missense mutations in HRAS are causative for Costello syndrome, with the c.34G?>?A (p.G12S) mutation as the most commonly found alteration. In the majority of affected individuals pathogenic sequence changes appeared de novo, however, two individuals with somatic mosaicism for the HRAS mutation have been reported. Here, we describe a boy with somatic mosaicism for the c.34G?>?A mutation in HRAS. Allelic quantitation revealed the mutation in approximately 58% of his lymphocytes; however, in DNA derived from buccal cells we could not detect the sequence change. The patient presented with the typical clinical findings of Costello syndrome such as increased birth weight, severe failure to thrive, characteristic facial appearance, and skin abnormalities. The dermatological anomalies were remarkable as he showed severe skin laxity with wrinkling of skin on all parts of the body due to loss of subcutaneous fat that decreased significantly by age 13 months. This case further adds to the phenotypic variability seen in patients with somatic mosaicism for an HRAS mutation and highlights the awareness of mosaic mutations in Costello syndrome when molecular testing is performed. © 2010 Wiley-Liss, Inc.

Hydrocephalus is a clinically and genetically heterogeneous condition. Individuals with posterior fossa abnormalities have an increased risk of developing hydrocephalus. The Dandy-Walker malformation, Dandy-Walker variant, and mega-cisterna magna (MCM) seem to represent a continuum of developmental anomalies of the posterior fossa. Here we describe the natural clinical history and the radiological features of a family with autosomal or X-linked dominant inheritance of MCM and hydrocephalus of variable severity. The affected family members demonstrate similar structural brain abnormalities including midline cyst, colpocephaly, MCM with a large posterior fossa and minimal vermian hypoplasia. The cognitive development of the affected individuals is normal. L1CAM and FOXC1 gene involvement in the pathogenesis of the disease in this family was excluded. The rare possibility of autosomal dominant or X-linked dominant inheritance and variable penetrance and expressivity must always be considered in genetic counseling of families with hereditary hydrocephalus. © 2010 Wiley-Liss, Inc.

BACKGROUND: Infant leukemia is rare and quite distinct from other childhood leukemias. Differentiating between leukemia and transient myeloproliferative disorder (TMD) in phenotypically normal infants is sometimes difficult. The clinical features and molecular analyses for the fusion transcripts of mixed lineage leukemia (MLL) gene rearrangement in infant leukemia have not been well documented in the Chinese population.

PROCEDURE: Forty-five consecutive infants diagnosed with leukemia between 1995 and 2007 in a tertiary medical center in Taiwan were studied. Acute lymphoblastic leukemia (ALL) was diagnosed in 23 infants, acute myeloid leukemia (AML) in 21 (including TMD in 4), and juvenile myelomonocytic leukemia (JMML) in 1.

RESULTS: The median white count at diagnosis was higher in ALL than in AML (154.4?×?10(9)/l vs. 58.3?×?10(9)/l, P?=?0.05). Chromosome 11q23/MLL abnormalities were present in 77% of ALL and 31% of AML. The 5-year event-free survival (EFS) in infant ALL and AML showed no difference (18% vs. 12%, respectively). The only independent predictor of an adverse prognosis among infants diagnosed with ALL was high presenting white count???100?×?10(9)/l (P?=?0.05). However, no factor was associated with an adverse outcome for infants with AML.

CONCLUSIONS: The molecular assessments and prognostic factors of infant leukemia in Taiwan mirror those in developed Western countries. Continued molecular investigations and development of more effective therapies are needed. Pediatr Blood Cancer. 2010;55:1264-1271. © 2010 Wiley-Liss, Inc.

Presence of bacterial DNA in noninfected patients with cirrhosis and ascites is associated with a marked inflammatory response including activation of the inducible form of nitric oxide synthase and release of nitric oxide, similar to that observed in patients with spontaneous bacterial peritonitis. Although presence of bacterial DNA is associated with an impaired prognosis, no information is available regarding its hemodynamic consequences. Systemic and hepatic hemodynamics before and after a liquid test meal were assessed in a series of 75 noninfected patients with cirrhosis (55 with ascites). Bacterial DNA was measured by polymerase chain reaction. Bacterial DNA was detected only in patients with ascites. Clinical data and liver function were similar in ascitic patients with presence (n = 21) or absence of bacterial DNA (n = 34). Bacterial-DNA(+) patients had significantly lower mean arterial pressure (P = 0.002) and systemic vascular resistance (P = 0.03) than bacterial-DNA(-) patients. Cardiac output, cardiopulmonary pressures, hepatic venous pressure gradient (HVPG), and hepatic blood flow were similar in both groups. Thirty minutes after the test meal, in response to increased blood flow caused by postprandial hyperemia, there was a significantly greater increase in HVPG and impaired hepatic vasorelaxation in bacterial-DNA(+) as compared with bacterial-DNA(-) patients, which indicates hepatic endothelial dysfunction. Indeed, the increase in HVPG after the test meal significantly correlated with serum bacterial DNA concentration. Conclusion: Presence of bacterial DNA, a marker of bacterial translocation, is associated with aggravation of peripheral vasodilation and with worsening of intrahepatic endothelial dysfunction. (HEPATOLOGY 2010;.).

HISTORY AND ADMISSION FINDINGS: In patients with glucose-6-phosphatase dehydrogenase (G6PD) deficiency (favism) jaundice is usually caused by hemolysis due to stress, infection or following the application of drugs. We report on a 74-year-old Italian with known G6PD deficiency complaining of jaundice, weight loss and abdominal pain. Physical examination revealed jaundice of the eyes. Scrotal examination by palpation and ultrasound showed no abnormalities.

INVESTIGATIONS: Serum levels of beta-human chorionic gonado-tropin and alpha-fetoprotein were within normal limits, total bilirubin was extremely elevated, with predominant direct bilirubin. Abdominal ultrasound showed posthepatic blockage of bile flow with a dilated ductus hepatocholedochus (DHC) in the absence of gallstones. Enlarged, multiple contrast-stained paraaortic and retroperitoneal lymph nodes were detected by endoscopic ultrasound and magnetic resonance imaging. Due to failed endoscopic retrograde cholangiopancreatography, visualization of the biliary tree by percutaneous transhepatic cholangiography (PTC) was performed showing an occlusion of the DHC. THERAPY AND COURSE: After successful stent-implantation by PTC with decompression of the biliary tree, the jaundice disappeared. Computer tomography-guided percutaneous biopsy of a retroperitoneal lymph node was performed for histological evaluation showing a primary extragonadal nonseminomatous germ cell tumor. According to the histology (embryonic carcinoma) and clinical stage of the tumor systemic chemotherapy was initiated including cisplatin, etoposide and ifosfamide. After the first cycle of chemotherapy the patient suffered from pneumonia leading to septic shock. Twenty-seven days after admission, the patient died of multiple organ failure.

CONCLUSION: Extragonadal germ-cell tumor presenting as retroperitoneal lymph nodes with obstructive jaundice has to be considered in the differential diagnosis of cholestasis.

© Georg Thieme Verlag KG Stuttgart · New York.

Pregnancy is a unique situation where significant physiological changes in all maternal organ systems take place. Most of these changes return to normal after delivery. During normal pregnancy the hemostatic balance changes in the direction of hypercoagulability, thus decreasing bleeding complications at time of delivery. The pregnancy-associated hypercoagulability sets a foundation for hemostatic abnormalities during pregnancy and may be associated with pregnancy complications. Assessment of the hemostatic status in pregnancy and its complications can be critical to diagnosis and management not only within the obstetric ward but in trauma, anesthesia, and other situations. Conventional global tests such as prothrombin time and activated partial thromboplastin time cannot define this status appropriately, and full assessment requires measurements of several parameters. Thromboelastography (TEG) is a global hemostatic test that can analyze both coagulation and fibrinolysis. The technique has been available since the 1940s, but only recently has it shown great impact within the clinical practice arena. TEG measures the interactive dynamic coagulation process from the initial fibrin formation to platelet interaction and clot strengthening to fibrinolysis, which makes it superior to other conventional tests. In addition, TEG can guide therapy by documenting changes in coagulation in vitro before a therapy is instituted and also by helping the clinician make critical decisions. Despite the clear value as a test for monitoring hemostatic status of pregnancy-related complications, TEG is still underused for reasons such as poor awareness regarding the technique and interpretations, lack of full standardization, and the unavailability of large clinical studies. However, the fact remains that TEG is undoubtedly attractive to both researchers and clinicians, particularly in a point-of-care setting. We hope that much more investment is directed to TEG studies in both experimental and clinical fields to improve applications and promote use, especially with respect to clinical decision making in pregnancy-related complications.

© Thieme Medical Publishers.

Current recommendations for resuscitation of the critically injured patient are limited by a lack of point-of-care (POC) assessment of coagulation status. Accordingly, the potential exists for indiscriminant blood component administration. Furthermore, although thromboembolic events have been described shortly after injury, the time sequence of post-injury coagulation changes is unknown. Our current understanding of hemostasis has shifted from a classic view, in which coagulation was considered a chain of catalytic enzyme reactions, to the cell-based model (CBM), representing the interplay between the cellular and plasma components of clot formation. Thromboelastography (TEG), a time-sensitive dynamic assay of the viscoelastic properties of blood, closely parallels the CBM, permitting timely, goal-directed restoration of hemostasis via POC monitoring of coagulation status. TEG-based therapy allows for goal-directed blood product administration in trauma, with potential avoidance of the complications resulting from overzealous component administration, as well as the ability to monitor post-injury coagulation status and thromboprophylaxis. This overview addresses coagulation status and thromboprophylaxis management in the trauma patient and the emerging role of POC TEG.

© Thieme Medical Publishers.

Prenatal exposure to alcohol and stimulants negatively affects the developing trajectory of the central nervous system in many ways. Recent advances in neuroimaging methods have allowed researchers to study the structural, metabolic, and functional abnormalities resulting from prenatal exposure to drugs of abuse in living human subjects. Here we review the neuroimaging literature of prenatal exposure to alcohol, cocaine, and methamphetamine. Neuroimaging studies of prenatal alcohol exposure have reported differences in the structure and metabolism of many brain systems, including in frontal, parietal, and temporal regions, in the cerebellum and basal ganglia, as well as in the white matter tracts that connect these brain regions. Functional imaging studies have identified significant differences in brain activation related to various cognitive domains as a result of prenatal alcohol exposure. The published literature of prenatal exposure to cocaine and methamphetamine is much smaller, but evidence is beginning to emerge suggesting that exposure to stimulant drugs in utero may be particularly toxic to dopamine-rich basal ganglia regions. Although the interpretation of such findings is somewhat limited by the problem of polysubstance abuse and by the difficulty of obtaining precise exposure histories in retrospective studies, such investigations provide important insights into the effects of drugs of abuse on the structure, function, and metabolism of the developing human brain. These insights may ultimately help clinicians develop better diagnostic tools and devise appropriate therapeutic interventions to improve the condition of children with prenatal exposure to drugs of abuse.