Home About us Contact
|
Home About us Contact | ||
|
|
||
Structural Malformation (structural + malformation)
Selected AbstractsCurrent recommendations for the molecular evaluation of newly diagnosed holoprosencephaly patients,,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2010Daniel E. Pineda-Alvarez§ Abstract Holoprosencephaly (HPE) is the most common structural malformation of the developing forebrain in humans and is typically characterized by different degrees of hemispheric separation that are often accompanied by similarly variable degrees of craniofacial and midline anomalies. HPE is a classic example of a complex genetic trait with "pseudo"-autosomal dominant transmission showing incomplete penetrance and variable expressivity. Clinical suspicion of HPE is typically based upon compatible craniofacial findings, the presence of developmental delay or seizures, or specific endocrinological abnormalities, and is then followed up by confirmation with brain imaging. Once a clinical diagnosis is made, a thorough genetic evaluation is necessary. This usually includes analysis of chromosomes by high-resolution karyotyping, clinical assessment to rule-out well recognized syndromes that are associated with HPE (e.g., Pallister-Hall syndrome, Smith-Lemli-Opitz syndrome and others), and molecular studies of the most common HPE associated genes (e.g., SHH, ZIC2 and SIX3). In this review, we provide current step-by-step recommendations that are medically indicated for the genetic evaluation of patients with newly diagnosed HPE. Moreover, we provide a brief review of several available methods used in molecular diagnostics of HPE and describe the advantages and limitations of both currently available and future tests as they relate to high throughput screening, cost, and the results that they may provide. Published 2010 Wiley-Liss, Inc. [source] Abnormal sterol metabolism in holoprosencephaly,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2010Dorothea Haas Abstract Holoprosencephaly (HPE) is the most common structural malformation of the developing forebrain in humans. The HPE phenotype is extremely variable and the etiology is heterogeneous. Among a variety of embryological toxins that can induce HPE, inhibitors, and other pertubations of cholesterol biosynthesis have been shown to be important factors, most likely because cholesterol is required in the Sonic hedgehog signaling cascade. Decreased levels of maternal cholesterol during pregnancy increase the risk for preterm delivery, but they are not associated with congenital malformations. However, if the fetus is affected by an inborn error of endogenous cholesterol synthesis, a reduction of maternal cholesterol concentration and cholesterol transport over the placenta aggravates the phenotypic expression. Exposure to lipophilic statins in early pregnancy may be associated with a substantial risk for structural CNS defects. © 2010 Wiley-Liss, Inc. [source] Diagnostic yield by supplementing prenatal metaphase karyotyping with MLPA for microdeletion syndromes and subtelomere imbalancesPRENATAL DIAGNOSIS, Issue 10 2010S. Kjaergaard Abstract Objective The aim of the study was to retrospectively assess the relevance of using multiplex ligation-dependent probe amplification (MLPA) for detection of selected microdeletion syndromes (22q11, Prader,Willi/Angelman, Miller,Dieker, Smith,Magenis, 1p-, Williams), the reciprocal microduplication syndromes and imbalance at the subtelomere regions of chromosomes in a routine prenatal setting. Method A total of 530 prenatal samples were analysed by commercial MLPA kits (SALSA P064, P036 and P069) in addition to rapid aneuploidy testing and G-band karyotyping. Results Among the prenatal samples with a normal metaphase karyotype, nine submicroscopic imbalances were detected: seven 22q11 deletions (Velocardiofacial/DiGeorge syndrome), one 15q11deletion (Prader,Willi syndrome) and one terminal deletion of the short arm of chromosome 4 (Wolf,Hirschhorn syndrome). All imbalances were found in amniocentesis (AC) taken due to fetal structural malformation and/or other ultrasound scan (US) detected abnormality. The diagnostic yield was 4.1% in the subgroup with structural malformation and 1.6% in the subgroup with other US abnormality. Conclusion The data set substantiates that additional MLPA analyses for selected microdeletions and subtelomere imbalances are valuable in routine prenatal diagnostics, when a malformation(s) and/or other abnormalities are detected by US. In contrast, the additional MLPA analyses gave no diagnostic yield in case of increased nuchal translucency (NT). Copyright © 2010 John Wiley & Sons, Ltd. [source] The use of combined ultrasound and magnetic resonance imaging in the detection of fetal anomaliesPRENATAL DIAGNOSIS, Issue 5 2010Xiomara M. Santos Abstract Objective To compare the referral diagnosis based on prenatal ultrasound to diagnoses made following combined ultrasound (US) and magnetic resonance imaging (MRI) evaluation at the Texas Children's Fetal Center (TCFC) and postnatal diagnosis. Methods We performed a retrospective review of patients referred to the TCFC between September 2001 and July 2007 with a fetal structural malformation. Data were abstracted to compare the referral diagnosis to TCFC imaging diagnoses and both were compared to postnatal diagnosis. Results Two hundred and twenty-four patients were referred who had a fetal US and MRI at TCFC. The most frequent indications were for abnormalities of the central nervous system (38%) and lung/thoracic cavity (34%), with congenital diaphragmatic hernia (CDH) the single most common referral diagnosis (n = 39; 17%). In 99 cases (42.7%) the referral diagnosis was concordant with the post-referral diagnosis, however, in 68 cases (29.3%) the post-referral diagnosis changed completely, and in 65 cases (28%) additional findings were discovered. Prenatal diagnoses following imaging at TCFC were concordant with postnatal diagnoses in 94.9% of cases. Conclusions Combined ultrasound and MRI provides additional diagnostic information or a corrected diagnosis in 57% of cases over the referral ultrasound diagnosis. Copyright © 2010 John Wiley & Sons, Ltd. [source] Hemangiomas: Evaluation and TreatmentDERMATOLOGIC SURGERY, Issue 5 2001Scott M. Dinehart MD Background. Hemangiomas are common skin tumors of infancy that have undergone recent changes in nomenclature, methods of evaluation, and treatment. Objective. To review the nomenclature, epidemiology, evaluation, and treatment of common hemangiomas. Methods. A literature search was conducted utilizing MEDLINE and the Cochrane library databases. Text search words used were "hemangioma" and "infancy." The clinical experience of the authors was also used to formulate the review. Results. There have been many advances in nomenclature and therapeutic options for children with hemangiomas. Hemangiomas are proliferative tumors of infancy that should be distinguished from structural malformations, such as port-wine stains and lymphangiomas. Conclusion. Natural involution remains a viable treatment option for the majority of patients with uncomplicated hemangiomas. Excisional surgery, laser, and pharmacologic remedies are indicated for a subset of complicated hemangioma patients. [source] From malformations to molecular mechanisms in the male: three decades of research on endocrine disrupters,APMIS, Issue 4 2001John A. McLachlan For three decades, we have known that estrogens alter the development of the mammalian reproductive system in predictable ways. In mice exposed prenatally to diethylstilbestrol (DES) or other estrogens, the male offspring exhibit structural malformations including cryptorchidism, epididymal cysts and retained Mullerian ducts. The estrogen-associated alterations in the genital tract phenotype can be usefully considered as a model called Developmental Estrogenization Syndrome. While estrogen treatment during critical periods of morphogenesis of the male reproductive system has been associated with these changes, the mechanisms at the molecular level are still being discovered. Parallel findings on the hormones involved in Mullerian duct regression and testicular descent have helped guide research on the mechanisms of developmental estrogenization of the male. Cellular localization of molecular signals associated with key steps in genital tract development, use of mice with gene disruption, and knowledge of the mechanisms underlying persistent changes in gene expression are beginning to provide a blue print for both the physiological role and pathological effects of estrogens in reproductive tract development. Since many of the same biological principles underlie genital tract morphogenesis in mammals, one may expect some of the same changes in males of other species exposed to estrogen during the appropriate developmental periods. [source] Differential risks to males and females for congenital malformations among 2.5 million California births, 1989,1997BIRTH DEFECTS RESEARCH, Issue 12 2003Gary M. Shaw Abstract BACKGROUND Although many studies have observed variations in the prevalence of specific malformations by sex, there is a lack of population-based data on potential malformation prevalence differences by sex at birth. METHODS Our objective was to explore differences in the prevalence of structural congenital malformation phenotypes between sexes in a California population of 2.5 million live- and stillbirths, using data from a population-based active surveillance system. Ascertainment was performed among offspring of California women who delivered in nonmilitary hospitals during the period of 1989,1997. Malformations were grouped according to the four-digit malformation codes of the British Pediatric Association. RESULTS Overall, 32,619 males and 21,835 females were considered to have structural congenital malformations, with prevalences of 2.52% and 1.76%, respectively. Thus, males demonstrated a malformation prevalence that was 22% higher than that in females. Using a criterion of a 40% increase or decrease in the relative risk for males, increased risks for 15 and decreased risks for 17 specific malformation categories were observed. Increased risks were associated with most organ systems, with the notable exception of the nervous system (increased risks for nervous system malformations were observed among female births). Risks were not substantially influenced by adjusting for maternal age, race/ethnicity, parity, or education. CONCLUSIONS Our observations extend the relatively few studies that have investigated differential prevalences of a large number of specific structural malformations between male and female births. Birth Defects Research (Part A) 67:000,000, 2003. © 2003 Wiley-Liss, Inc. [source] | |||||||||||||