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Malformation Syndromes (malformation + syndrome)
Selected AbstractsLeft Coronary Artery Arteriovenous Malformation Presenting as a Diastolic Murmur with Exercise Intolerance in a Child with a Suspected Familial Vascular Malformation SyndromeCONGENITAL HEART DISEASE, Issue 3 2007Valerie A. Schroeder MD Abstract Objective., Intracardiac arteriovenous malformations are rare and may be associated with sudden death in adults. This case report describes an intracardiac left coronary arteriovenous malformation in a 7-year-old boy with a suspected familial cutaneous vascular malformation syndrome. The patient presented with a diastolic murmur, exercise intolerance, chest pain, and a left ventricular mass. Methods., The left ventricular mass was initially identified by echocardiography. Subsequently, a computed tomography scan revealed the vascular nature of the lesion. We hypothesized that the lesion represented either an arteriovenous malformation (AVM) or a hemangioma. These lesions are thought to cause coronary steal and myocardial dysfunction. Skin biopsies of the patient's cutaneous lesions revealed capillary hyperplasia, which was not consistent with either hemangioma or AVM. Thus, a surgical biopsy and partial resection of the mass was performed. Results., The surgical pathology of the cardiac mass was consistent with an AVM. Within 6 months following partial resection of the mass, the patient unexpectedly developed a left ventricular pseudoaneurysm at the resection site and required re-operation. Although a portion of the mass remains, both the patient's chest pain and exercise tolerance have improved subjectively. Conclusion., Patients with cutaneous vascular malformations and diastolic murmurs, as well as cardiac symptoms, should undergo echocardiography or alternative imaging modalities to screen for treatable pathological myocardial vascular malformations. [source] Heterozygous SOX9 Mutations Allowing for Residual DNA-binding and Transcriptional Activation Lead to the Acampomelic Variant of Campomelic Dysplasia,HUMAN MUTATION, Issue 6 2010Alex Staffler Abstract Campomelic dysplasia is a malformation syndrome with multiple symptoms including characteristic shortness and bowing of the long bones (campomelia). CD, often lethal due to airway malformations, is caused by heterozygous mutations in SOX9, an SRY-related gene regulating testis and chondrocyte development including expression of many cartilage genes such as type II collagen. Male to female sex reversal occurs in the majority of affected individuals with an XY karyotype. A mild form without campomelia exists, in which sex-reversal may be also absent. We report here two novel SOX9 missense mutations in a male (c.495C>G; p.His165Gln) and a female (c.337A>G; p.Met113Val) within the DNA-binding domain leading to non-lethal acampomelic CD. Functional analyses of mutant proteins demonstrate residual DNA-binding and transactivation of SOX9-regulated genes. Combining our data and reports from the literature we postulate a genotype-phenotype correlation: SOX9 mutations allowing for residual function lead to a mild form of CD in which campomelia and sex reversal may be absent. © 2010 Wiley-Liss, Inc. [source] Mutation spectrum of Meckel syndrome genes: one group of syndromes or several distinct groups?,HUMAN MUTATION, Issue 8 2009Jonna Tallila Abstract Meckel syndrome (MKS) is a lethal malformation syndrome that belongs to the group of disorders that are associated with primary cilia dysfunction. Total of five genes are known to be involved in the molecular background of MKS. Here we have systematically analyzed all these genes in a total of 29 MKS families. Seven of the families were Finnish and the rest originated from elsewhere in Europe. We found 12 novel mutations in 13 families. Mutations in the MKS genes are also found in other syndromes and it seems reasonable to assume that there is a correlation between the syndromes and the mutations. To obtain some supportive information, we collected all the previously published mutations in the genes to see whether the different syndromes are dictated by the nature of the mutations. Based on this study, mutations play a role in the clinical phenotype, given that the same allelic combination of mutations has never been reported in two clinically distinct syndromes. © 2009 Wiley-Liss, Inc. [source] Age distributions, birth weights, nephrogenic rests, and heterogeneity in the pathogenesis of Wilms tumorPEDIATRIC BLOOD & CANCER, Issue 3 2006Norman E. Breslow PhD Abstract Background The National Wilms Tumor Study (NWTS) constitutes a unique resource for study of clinical, pathologic, and epidemiologic features of Wilms tumor (WT). Procedure Data from NWTS-3,4,5 were compiled for 7,455 patients with tumors of favorable (FH) or anaplastic (AH) histology. The associations of birth weight (BW) and age-at-onset with gender, intralobar (ILNR), and perilobar (PLNR) nephrogenic rests, tumor focality, congenital malformation syndromes, and tumor histology were analyzed using descriptive statistics and linear regression. Results Mean BWs for male and female patients without PLNR were 3.52 and 3.36 kg, respectively, and for those with PLNR were 0.12 kg and 0.15 kg heavier. Mean age was 45 months for males with no rests whose tumors were unifocal and of triphasic favorable histology. ILNR or multifocality decreased the mean age by 18 and 10 months, respectively, whereas female gender, blastemal/FH or AH increased it by 3, 10, and 16 months. Over 90% of multifocal tumors occurred in the presence of demonstrated ILNR or PLNR or both. The apparent bimodality of the age distributions and later mean ages-at-onset for females with both unifocal and multifocal tumors were explained in part by the relative deficit in females of ILNR versus PLNR-associated tumors. Conclusions These observations support the view that there are multiple pathways to Wilms tumorigenesis. They will facilitate selection of informative subgroups of patients for molecular analysis that may serve to identify the putative pathway for the majority of patients who cannot be classified provisionally on the basis of ILNR or PLNR. Pediatr Blood Cancer 2006;47:260,267. © 2006 Wiley-Liss, Inc. [source] The molecular genetics of holoprosencephaly,,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2010Erich Roessler§ Abstract Holoprosencephaly (HPE) has captivated the imagination of Man for millennia because its most extreme manifestation, the single-eyed cyclopic newborn infant, brings to mind the fantastical creature Cyclops from Greek mythology. Attempting to understand this common malformation of the forebrain in modern medical terms requires a systematic synthesis of genetic, cytogenetic, and environmental information typical for studies of a complex disorder. However, even with the advances in our understanding of HPE in recent years, there are significant obstacles remaining to fully understand its heterogeneity and extensive variability in phenotype. General lessons learned from HPE will likely be applicable to other malformation syndromes. Here we outline the common, and rare, genetic and environmental influences on this conserved developmental program of forebrain development and illustrate the similarities and differences between these malformations in humans and those of animal models. Published 2010 Wiley-Liss, Inc. [source] Evaluation of 2407 fetuses in a Turkish populationPRENATAL DIAGNOSIS, Issue 9 2007Gülay Ceylaner Abstract Objectives Congenital anomalies and intrauterine fetal death (IUFD) are frequent problems in pregnancies. Detection of the etiology is important for genetic counseling, and presenting the geographic distribution of the causes of disorders is necessary for a national policy on precautions. Here, we report the findings of terminated fetuses due to IUFD and congenital anomalies in Turkish population. Methods Physical examinations of fetuses and genetic evaluations of families were done. X-ray studies and autopsy were done in the event of necessity. Findings of these studies were combined with prenatal ultrasound results. All cases were classified according to ICD-10. Results The number of fetuses examined was 2407. Out of these, 1268 fetuses had congenital anomalies. Neurologic anomalies and musculoskeletal system malformations were the most frequent disorders. Specific diagnoses were possible in 64% of all multiple malformation syndromes. Abnormal findings were detected in 18.8% of IUFD fetuses. Nine percent had congenital anomalies and 5.2% had cord complications. The percentage of twins and triplets was 7.5% and 13% of them had anomalies. Conclusion Postmortem evaluation is useful to detect findings necessary for genetic counseling. Our protocol is effective especially in fetuses with congenital anomalies but it can detect only some of the fetal reasons in IUFD cases. A more detailed protocol is needed to investigate IUFD cases. Copyright © 2007 John Wiley & Sons, Ltd. [source] Genetic skeletal disorders of the fetus and infant: Pathologic and molecular findings in a series of 41 cases,BIRTH DEFECTS RESEARCH, Issue 10 2009Anastasia E. Konstantinidou Abstract BACKGROUND: Genetic skeletal disorders of the fetus and infant are a large group of genetic disorders, comprising the groups formerly assigned as skeletal dysplasias (osteochondrodysplasias), dysostoses, and malformation syndromes with a skeletal component. Genetic skeletal disorders may be prenatally detected by ultrasonography or result in intrauterine or early postnatal death, constituting one difficult diagnostic field met by the pathologist who performs the perinatal autopsy. METHODS: In this retrospective study, we have gathered radiologic, physical, histopathologic, and molecular data regarding 41 cases of genetic skeletal disorders diagnosed among 1980 fetal and perinatal autopsies over a 10-year period. RESULTS: Our series of cases were classified according to the 2006 Nosology and Classification of Genetic Skeletal Disorders. The overall frequency of genetic skeletal disorders was 1:48 autopsies. The FGFR3 group and osteogenesis imperfecta type 2 were the more frequently encountered disorders. The mean gestational age at autopsy was 21.9 weeks (range, 12,37 weeks). A final diagnosis was obtained in 95% of cases. Genetic skeletal disorders were detected by prenatal ultrasound in 90% of cases, with a correct typing of the disorder achieved in only 34%. Molecular analysis was confirmative in 5 cases. CONCLUSIONS: The central role of the perinatal pathologist in collaboration with specialized services is essential for the correct interpretation of the radiologic, physical, and histopathologic findings, to accurately classify specific types of genetic skeletal disorders and enable genetic counseling. Birth Defects Research (Part A), 2009. © 2009 Wiley-Liss, Inc. [source] | |||||||||||||