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Genital Anomalies (genital + anomaly)
Selected AbstractsZFHX1B mutations in patients with Mowat-Wilson syndrome,HUMAN MUTATION, Issue 4 2007Florence Dastot-Le Moal Abstract Mowat-Wilson syndrome (MWS) is a recently delineated mental retardation (MR)-multiple congenital anomaly syndrome, characterized by typical facies, severe MR, epilepsy, and variable congenital malformations, including Hirschsprung disease (HSCR), genital anomalies, congenital heart disease (CHD), and agenesis of the corpus callosum (ACC). It is caused by de novo heterozygous mutations or deletions of the ZFHX1B gene located at 2q22. ZFHX1B encodes Smad-interacting protein-1 (SMADIP1 or SIP1), a transcriptional corepressor involved in the transforming growth factor-, signaling pathway. It is a highly evolutionarily conserved gene, widely expressed in embryological development. Over 100 mutations have been described in patients with clinically typical MWS, who almost always have whole gene deletions or truncating mutations (nonsense or frameshift) of ZFHX1B, suggesting that haploinsufficiency is the basis of MWS pathology. No obvious genotype,phenotype correlation could be identified so far, but atypical phenotypes have been reported with missense or splice mutations in the ZFHX1B gene. In this work we describe 40 novel mutations and we summarize the various mutational reports published since the identification of the causative gene. Hum Mutat 28(4), 313,321, 2007. © 2007 Wiley-Liss, Inc. [source] Epidemiology of holoprosencephaly: Prevalence and risk factors,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2010Iêda M. Orioli Abstract The wide variation in cerebral and facial phenotypes and the recognized etiologic heterogeneity of holoprosencephaly (HPE) contribute to the observed inter-study heterogeneity. High lethality during the early stages of embryonic and fetal development makes HPE detection age dependent. By reviewing 21 HPE epidemiologic articles, the observed prevalence rate differences can be largely explained by the pregnancy outcome status of the studied cohort: livebirth, stillbirth, and terminations of pregnancy (TOPs): lower than 1 per 10,000 when live and still births were included, higher when TOPs were included, and between 40 and 50 per 10,000 in two classical Japanese studies on aborted embryos. The increasing secular trend observed in some studies probably resulted from an increasing use of prenatal sonography. Ethnic variations in birth prevalence rates (BPRs) could occur in HPE, but the available data are not very convincing. Higher BPRs were generally observed in the less favored minorities (Blacks, Hispanics, Pakistanis), suggesting a bias caused by a lower prenatal detection rate of HPE, and consequently less TOPs. Severe ear defects, as well as microstomia, were part of the spectrum of HPE. Non-craniofacial anomalies, more frequently associated with HPE than expected, were genital anomalies (24%), postaxial polydactyly (8%), vertebral defects (5%), limb reduction defects (4%), and transposition of great arteries (4%). The variable female predominance, found in different HPE studies, could also depend on the proportion of early conceptions in each study sample, as males are more likely to be lost through spontaneous abortions. © 2010 Wiley-Liss, Inc. [source] The Biology of the Development of the Genital Organs.ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2005A Multimedia Teaching Program In my presentation, I review the sexual differentiation from the genetic sex until the appearance of the external genitalia and the developmental anomalies to use an animated cartoon. The first critical stage of sexual differentiation occurs at the moment of fertilization, when the genetic sex of the zygote is determined by the nature of the sex chromosome contributed by the sperm. Although an XY zygote is destined to become a male, no distinctive differences between the early development of male and female embryos have been noted. This is accomplished after migration of the primordial germ cell into the early gonad. Because of the early commonality of genital structures, anomalies are the result of abnormal retention or loss of appropriate genital structures. Therefore, most genital anomalies are some form of intersex. During the early differentiation of the gonads, while the mesonephros is still the dominant excretory organ, the gonads arise as ridge like thickenings (gonadal ridge) on its ventromedial face. Differentiation of the indifferent gonads into ovaries or testes occurs after the arrival of the primordial germ cells. The primordial germ cells arise from the endodermal cells of the yolk. The principal function of the Y chromosome is to direct the differentiation of the presented indifferent gonad into a testis from the sixth week, while two X chromosome are presented the ovaries start to develop, from the 12th week. The next and most obvious phase in sexual differentiation of the embryo is the differentiation of the somatic sex. The early embryo develops a dual set of potential genital ducts, one is the original mesonephric (Wolff ) ducts, which persists after degeneration of the mesonephros as an excretory organ, and the another is newly formed pair of ducts called the paramesonephric (Müllerian) ducts. Under the influence of testosterone secreted by the testes, the mesonephric ducts develop into the duct system through which the spermatozoa are conveyed from the testes to the urethra. The potentially female paramesonephric ducts regress under the influence of another product of the embryonic testes, the Müllerian inhibitory factor, a glycoprotein secreted by the Sertoli cells. In genetically female embryos, neither testosterone nor Müllerian inhibitory factor are secreted by the gonads. In the absence of testosterone the mesonephric ducts regress and lack of Müllerian inhibitory factor permits the paramesonephric ducts to develop into oviducts, the uterus and part of the vagina. The next stage is the development of the external genitalia. In very young embryos, a vaguely outlined elevation known as the genital eminence can be seen in the midline, just cephalic to the proctodeal depression. This is soon differentiated into a central prominence (genital tubercle) closely flanked by a pair of folds (genital folds) extending toward the proctodeum. Somewhat farther to either side are rounded elevation known as the genital swellings. From this common starting point the external genitalia of both sex differentiate. If the individual is to develop into a male the genital tubercle, under the influence of dihydrotestosterone, becomes greatly elongated to form the penis and the genital swellings become enlarged to form the scrotal pouches. During the growth of the penis a groove develops along the entire length of its caudal face and is continuous with the slit-like opening of the urogenital sinus. This groove later becomes closed over by a ventral fusion of the genital folds, establishing the penile portion of the urethra. The portion of the urogenital sinus between the neck of the bladder and the original opening of the urogenital sinus becomes the prostetic urethra. In the female, the genital tubercle becomes the clitoris, the genital folds become the labia minora, and the genital swellings become the labia majora. The urethra in the female is derived from the urogenital sinus, being homologous with the prostatic portion of the male urethra. [source] The psychological impact of genital anomalies on the parents of affected childrenACTA PAEDIATRICA, Issue 3 2007A Duguid Abstract Background: There is scarce information on how parents cope with children with genital anomalies. Participants & methods: Twenty-six parents of 25 children with a median age of 0.5 years (r, 5 days,10.8 years) were recruited through the Scottish Genital Anomaly Network and had a quantitative assessment of parenting stress and coping patterns; a qualitative assessment by a semi-structured interview was also performed in19 parents. Results: In five parents, the total stress score was above the 85th centile, denoting clinical levels of stress. Three parents showed reduced coping pattern scores for social support, self-esteem and psychological stability and three showed a reduction in utilization of communication with medical professionals. The scores did not correlate with each other or the extent of genital anomaly in the child. Semi-structured interview analysis revealed parents' need for more knowledge about the imminent surgery, post-operative care and their desire for written information that could complement the time-restricted contact with the clinical team. Conclusion: In the majority of cases, parents did not display abnormal levels of stress or coping on quantitative assessment. The semi-structured interview provided further information about the parents' level of coping and potential for stress and highlighted the need for more effective exchange of clinical information at a critical period of the parent,child relationship. [source] | ||||||||||