Prenatal Sonographic Features of Miller-Dieker Syndrome

Miller-Dieker syndrome (MDS) is a contiguous gene deletion disorder involving genes on chromosome 17p13.3. Clinical manifestations include central nervous system (CNS) anomalies (mainly Type I lissencephaly), facial dysmorphism, growth restriction, profound mental retardation, seizure, and extracranial anomalies. The affected individuals often die in infancy or early childhood. Owing to the poor prognosis of MDS, early diagnosis of fetuses with MDS is important. Currently, ultrasound is regarded as a useful tool in prenatal detection of MDS, in addition to fetal magnetic resonance imaging. This article provides an overview of the reported prenatal sonographic features of MDS, including CNS anomalies (ventriculomegaly, agyria or lissencephaly, abnormal sylvian fissures, agenesis or dysgenesis of corpus callosum, and microcephaly), intrauterine growth restriction, polyhydramnios, cardiac anomalies, omphalocele, facial anomalies, and rare anomalies. Several diseases may have phenotypic overlaps with MDS, including Type I lissencephaly (Lissencephaly 1, Lissencephaly 2, and X-linked lissencephaly) and Type II lissencephaly. Increasing the awareness and knowledge of fetal structural anomalies associated with MDS on prenatal ultrasound will be helpful in the early detection, thus allowing appropriate genetic counseling and optimize clinical management

Prenatal Sonographic Features of Turner Syndrome

Turner syndrome (TS) was first described by Henry Turner in 1938 and was then known to be secondary to karyotypic variation of 45, X in 1959. Most conceptuses with TS spontaneously abort, and only 1% of these embryos survive to term. Fetuses with a pure and complete monosomy X often have more complicated anomalies than those with mosaicism and structural abnormalities in one X chromosome. Ultrasound has been reported to be a reliable tool in the prenatal diagnosis of TS. This article provides an overview of the common sonographic features of fetuses with TS, including cystic hygromas, increased nuchal translucency, non-immune hydrops fetalis, cardiovascular anomalies, urinary anomalies, short femur length, and other rare structural anomalies. Despite that some sonographic markers are transient and may be resolved later in gestation, detection of these markers in early pregnancy should remind obstetric clinicians of the importance of these predictors in TS. The prognosis for cases with TS detected in fetal life is relatively poor. In addition, several diseases may have phenotypic overlap with fetal TS, including non-TS-related cystic hygromas, non-TS-related non-immune hydrops fetalis and Noonan syndrome. Therefore, prenatal recognition of these sonographic features is of great help in karyotypic confirmation, and in appropriate genetic counseling and obstetric treatment

Prenatal Sonographic Features of Pallister-Killian Syndrome

Pallister-Killian syndrome (PKS), which is characterized by mental retardation, seizures, pigmentary skin lesions and dysmorphic facial features, is a rare chromosomal anomaly with the mosaic presence of an extra tissue-specific isochromosome 12p (mosaic tetrasomy 12p). Advanced maternal age is believed to be a risk factor for PKS. Ultrasound is a useful tool in the prenatal detection of characteristic findings associated with PKS. This article provides an overview of the prenatal sonographic features of PKS, including congenital diaphragmatic hernia, polyhydramnios, abnormal extremities, increased nuchal translucency or nuchal edema, cardiovascular anomalies, central nervous system anomalies, an abnormal facial profile, and other rare anomalies. Appropriate tissue samples and laboratory analytic techniques should be selected for an accurate prenatal diagnosis because of the instability of isochromosome 12p and the potentially incorrect interpretation as tetrasomy 21q on the traditional G-banded technique. Fryns syndrome, which has phenotypic overlap with PKS, is also discussed. Increasing awareness and knowledge of various anomalies of PKS on prenatal ultrasound would be helpful for the early detection of PKS. Definite diagnosis of fetuses with PKS could help clinical physicians in the decisionmaking process during the prenatal or postnatal periods

PRENATAL DIAGNOSIS OF MOS45,X/46,X,+MAR IN A FETUS WITH NORMAL MALE EXTERNAL GENITALIA AND A LITERATURE REVIEW

[[abstract]]Objective: Prenatal diagnosis of mos45,X/46,X,+mar is difficult in genetic counseling. Patients with the presence of a Y-derived marker may manifest male or female external genitalia. Here, we report a fetus with phenotypically male external genitalia of mos45,X/46,X,+mar. In addition, the cases with prenatally detected mos45,X/46,X,del(Y)(q11.2) and normal male external genitalia are reviewed. Case Report: A 30-year-old, primigravid woman was referred for amniocentesis because of an abnormal Down syndrome screening result at 20 weeks' gestation. Cytogenetic analysis showed mos45,X/46,X,+mar without a normal Y chromosome. Prenatal ultrasound detected symmetric intrauterine growth restriction and normal male external genitalia. After termination of the pregnancy, a phenotypically normal male fetus was delivered smoothly without apparent structural defects. Based on conventional G-banded analysis, the marker chromosome appeared as a Y chromosome that originated with a deleted Yq, designated as del(Y)(q11.2). Conclusion: Based on a literature review, the addition of fluorescence in situ hybridization and molecular analysis to the conventional cytogenetic techniques can provide more accurate identification of a Y chromosome aberration in the prenatal detection of mos45,X/46,X,+mar, thus allowing more appropriate genetic counseling for the family. [Taiwan J Obstet Gynecol 2009;48(3):292-295

Inhibition of Serine Protease Activity Protects Against High Fat Diet-Induced Inflammation and Insulin Resistance.

Recent evidence suggests that enhanced protease-mediated inflammation may promote insulin resistance and result in diabetes. This study tested the hypothesis that serine protease plays a pivotal role in type 2 diabetes, and inhibition of serine protease activity prevents hyperglycemia in diabetic animals by modulating insulin signaling pathway. We conducted a single-center, cross-sectional study with 30 healthy controls and 57 patients with type 2 diabetes to compare plasma protease activities and inflammation marker between groups. Correlations of plasma total and serine protease activities with variables were calculated. In an in-vivo study, LDLR-/- mice were divided into normal chow diet, high-fat diet (HFD), and HFD with selective serine protease inhibition groups to examine the differences of obesity, blood glucose level, insulin resistance and serine protease activity among groups. Compared with controls, diabetic patients had significantly increased plasma total protease, serine protease activities, and also elevated inflammatory cytokines. Plasma serine protease activity was positively correlated with body mass index, hemoglobin A1c, homeostasis model assessment-insulin resistance index (HOMA-IR), tumor necrosis factor-α, and negatively with adiponectin concentration. In the animal study, administration of HFD progressively increased body weight, fasting glucose level, HOMA-IR, and upregulated serine protease activity. Furthermore, in-vivo serine protease inhibition significantly suppressed systemic inflammation, reduced fasting glucose level, and improved insulin resistance, and these effects probably mediated by modulating insulin receptor and cytokine expression in visceral adipose tissue. Our findings support the serine protease may play an important role in type 2 diabetes and suggest a rationale for a therapeutic strategy targeting serine protease for clinical prevention of type 2 diabetes

Molecular epidemiology and emergence of worldwide epidemic clones of Neisseria meningitidis in Taiwan

BACKGROUND: Meningococcal disease is infrequently found in Taiwan, a country with 23 million people. Between 1996 and 2002, 17 to 81 clinical cases of the disease were reported annually. Reported cases dramatically increased in 2001–2002. Our record shows that only serogroup B and W135 meningococci have been isolated from patients with meningococcal disease until 2000. However, serogroup A, C and Y meningococci were detected for the first time in 2001 and continued to cause disease through 2002. Most of serogroup Y meningococcus infections localized in Central Taiwan in 2001, indicating that a small-scale outbreak of meningococcal disease had occurred. The occurrence of a meningococcal disease outbreak and the emergence of new meningococcal strains are of public health concern. METHODS: Neisseria meningitidis isolates from patients with meningococcal disease from 1996 to 2002 were collected and characterized by serogrouping, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The genetic relatedness and clonal relationship between the isolates were analyzed by using the PFGE patterns and the allelic profiles of the sequence types (STs). RESULTS: Serogroups A, B, C, W135, Y, and non-serogroupable Neisseria meningitidis were, respectively, responsible for 2%, 50%, 2%, 35%, 9%, and 2% of 158 culture-confirmed cases of meningococcal disease in 1996–2002. Among 100 N. meningitidis isolates available for PFGE and MLST analyses, 51 different PFGE patterns and 30 STs were identified with discriminatory indices of 0.95 and 0.87, respectively. Of the 30 STs, 21 were newly identified and of which 19 were found in serogroup B isolates. A total of 40 PFGE patterns were identified in 52 serogroup B isolates with the patterns distributed over several distinct clusters. In contrast, the isolates within each of the serogroups A, C, W135, and Y shared high levels of PFGE pattern similarity. Analysis of the allelic profile of the 30 STs suggested the serogroup B isolates be assigned into 5 clonally related groups/ clonal complexes and 7 unique clones. The ST-41/44 complex/Lineage 3, and the ST-3439 and ST-3200 groups represented 79% of the serogroup B meningococci. In contrast, isolates within serogroups A, serogroup W135 (and C), and serogroup Y, respectively, simply belonged to ST-7, ST-11, and ST-23 clones. CONCLUSION: Our data suggested that serogroup B isolates were derived from several distinct lineages, most of which could either be indigenous or were introduced into Taiwan a long time ago. The serogroup A, W135 (and C), and Y isolates, respectively, belonged to the ST-7, ST-11, and ST-23, and the represented clones that are currently the major circulating clones in the world and are introduced into Taiwan more recently. The emergence of serogroup A, C and Y strains contributed partly to the increase in cases of meningococcal disease in 2001–2002

Molecular and clinical analyses of 84 patients with tuberous sclerosis complex

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by the development of multiple hamartomas in many internal organs. Mutations in either one of 2 genes, TSC1 and TSC2, have been attributed to the development of TSC. More than two-thirds of TSC patients are sporadic cases, and a wide variety of mutations in the coding region of the TSC1 and TSC2 genes have been reported. METHODS: Mutational analysis of TSC1 and TSC2 genes was performed in 84 Taiwanese TSC families using denaturing high-performance liquid chromatography (DHPLC) and direct sequencing. RESULTS: Mutations were identified in a total of 64 (76 %) cases, including 9 TSC1 mutations (7 sporadic and 2 familial cases) and 55 TSC2 mutations (47 sporadic and 8 familial cases). Thirty-one of the 64 mutations found have not been described previously. The phenotype association is consistent with findings from other large studies, showing that disease resulting from mutations to TSC1 is less severe than disease due to TSC2 mutation. CONCLUSION: This study provides a representative picture of the distribution of mutations of the TSC1 and TSC2 genes in clinically ascertained TSC cases in the Taiwanese population. Although nearly half of the mutations identified were novel, the kinds and distribution of mutation were not different in this population compared to that seen in larger European and American studies

Epidemiological trend in inflammatory bowel disease in Taiwan from 2001 to 2015: a nationwide populationbased study

Background/Aims Incidences of inflammatory bowel disease (IBD), ulcerative colitis (UC), and Crohn’s disease (CD), have been increasing in Asia. In this study, we report the relevant clinical characteristics and determined the epidemiological trend of IBD in Taiwan from 2001 to 2015. Methods A retrospective study was conducted to analyze data recorded from January 2001 through December 2015 in the registered database compiled by the National Health Insurance and provided by the Ministry of Health and Welfare, Taiwan. Results A total of 3,806 patients with catastrophic IBD illness were registered from 2001 to 2015 in Taiwan (CD, 919; UC, 2,887). The crude incidence of CD increased from 0.17/100,000 in 2001 to 0.47/100,000 in 2015, whereas that of UC increased from 0.54/100,000 in 2001 to 0.95/100,000 in 2015. The prevalence of CD increased from 0.6/100,000 in 2001 to 3.9/100,000 in 2015, whereas that of UC increased from 2.1/100,000 in 2001 to 12.8/100,000 in 2015. The male-to-female ratio in the study sample was 2.19 for CD and 1.62 for UC. The median age of those registered with CD was lower than that of those registered for UC: 38.86 and 44.86 years, respectively. A significantly greater increase in CD incidence rate was identified among 20 to 39-year-old compared with other age groups. Conclusions Using Taiwan’s nationwide insurance database, we determined that the number of patients with CD increased more rapidly during the study period than the number of patients with UC, especially among age 20 to 39-year-old, resulting in a decreased UC-to-CD ratio