Long-term follow-up on MURCS (Müllerian duct, renal, cervical somite dysplasia) association and a review of the literature

Müllerian duct aplasia-renal aplasia-cervicothoracic somite dysplasia (MURCS) association is a unique development disorder with four common types of malformations that include uterine aplasia or hypoplasia, renal ectopy or agenesis, vertebral anomalies, and short stature. The majority of MURCS patients are diagnosed with primary amenorrhea from late-adolescence. However, a few cases with MURCS association are not well diagnosed during childhood and long-term outcomes are not well reported. We report a case of an 8-year-old girl with MURCS association who presented with recurrent urinary tract infections and multiple congenital malformations, and who was followed for 10 years until adulthood. MURCS association should be considered as one of the differential diagnoses when evaluating prepubertal females with vertebral and renal malformations.

Differences between NMRI and DBA/2J mice in the development of somites and susceptibility to methylnitrosourea-induced skeleton anomalies

ABSTRACT The development of DBA/2J mouse strain embryos is nearly 12 h - or 6 somite pairs - delayed as compared to the outbred NMRI mouse embryos of the same age on gestation days (GD) 8-12. To evaluate inter-strain differences in susceptibility to teratogens, dams were treated with methylnitrosourea (MNU, 5 mg/kg body weight i.p.) on defined gestation days (NMRI: GD 9, 91/2 or 10; DBA/2J: GD 10 or 101/2). Skeletal anomalies produced by MNU on both mouse strains varied with the GD of treatment. The pattern of anomalies produced by MNU on a given GD markedly differed between the two mouse strains, yet they were similar -with a few exceptions- when exposures at equivalent embryonic stages are compared. Findings from this study indicated that strain-dependent differences in the developmental stage of mouse embryos of the same gestational age occur, a possibility that has been often neglected when inter-strain differences in susceptibility to developmental toxicants are interpreted.

Magnetic Resonance Evaluation of Mullerian Remnants in Mayer-Rokitansky-Kuster-Hauser Syndrome

OBJECTIVE: To analyze magnetic resonance imaging (MRI) findings of Mullerian remnants in young females clinically suspected of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome in a primary amenorrhea workup. MATERIALS AND METHODS: Fifteen young females underwent multiplanar T2- and transverse T1-weighted MRI at either a 1.5T or 3.0T MR imager. Two gynecologic radiologists reached consensus decisions for the evaluation of Mullerian remnants, vagina, ovaries, and associated findings. RESULTS: All cases had bilateral uterine buds in the pelvic cavity, with unilateral cavitation in two cases. The buds had an average long-axis diameter of 2.64 +/- 0.65 cm. In all cases, bilateral buds were connected with fibrous band-like structures. In 13 cases, the band-like structures converged at the midline or a paramedian triangular soft tissue lying above the bladder dome. The lower one-third of the vagina was identified in 14 cases. Fourteen cases showed bilateral normal ovaries near the uterine buds. One unilateral pelvic kidney, one unilateral renal agenesis, one mild scoliosis, and three lumbar sacralization cases were found as associated findings. CONCLUSION: Typical Mullerian remnants in MRKH syndrome consist of bilateral uterine buds connected by the fibrous band-like structures, which converge at the midline triangular soft tissue lying above the bladder dome.

Laparoscopic and gasless laparoscopic sigmoid colon vaginoplasty in women with vaginal agenesis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In the past several decades we have seen multiple advances in the reconstruction for girls born with vaginal agenesis. This study aimed to evaluate the technical feasibility, anatomical and functional outcomes of one-stage laparoscopic and gasless laparoscopic vaginoplasty with sigmoid colon for the patients of vaginal agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome).</p><p><b>METHODS</b>We did a retrospective review of a total of 150 women with Mayer-Rokitansky-Kuster-Hauser syndrome treated at Beijing Anzhen Hospital, Capital Medical University from March 2006 to August 2010. The patients were divided into the CO2 pneumoperitoneum laparoscopic group and the abdominal wall lift of gasless laparoscopic group. Sigmoid colon vaginoplasty approaches were performed in all of the patients. The surgical techniques, perioperative results, complications, anatomical and functional outcomes of vaginoplasty were recorded.</p><p><b>RESULTS</b>All procedures were performed successfully. Significant differences in the operative time and intraoperative blood loss existed in the laparoscopic vaginoplasty group compared with the gasless laparoscopic vaginoplasty group. The patients who underwent sigmoid colon vaginoplasty had good cosmetic results without the problem of excessive mucus production. The postoperative complications were minimal. During a mean follow-up of 15.6 months, no stenosis or shrinkage was encountered. The subjective sexual satisfaction rate with the surgical outcomes in all patients was 83.3%.</p><p><b>CONCLUSIONS</b>Laparoscopic or gasless laparoscopic vaginoplasty with sigmoid colon are effective and feasible approaches for women with congenital vaginal agenesis. The procedures have satisfactory anatomical and functional results.</p>

Mayer-Rokitansky-Kuster-Hauser (MRKH) Syndrome in a Child with Idiopathic Precocious Puberty

Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a rare congenital disorder characterized by the congenital absence or hypoplasia of the uterus and the upper two thirds of the vagina due to mullerian duct malformation during embryogenesis. MRKH syndrome usually presents as primary amenorrhea in adolescence in females showing normal development of secondary sexual characteristics and a normal 46, XX karyotype. For this reason, MRKH syndrome usually remains undiagnosed until primary amenorrhea or difficulty in sexual intercourse occurs. In this study, a case of MRKH syndrome diagnosed in a child with idiopathic precocious puberty is reported.

Mayer-Rokitansky-Kuster-Hauser (MRKH) Syndrome in a Child with Idiopathic Precocious Puberty

Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a rare congenital disorder characterized by the congenital absence or hypoplasia of the uterus and the upper two thirds of the vagina due to mullerian duct malformation during embryogenesis. MRKH syndrome usually presents as primary amenorrhea in adolescence in females showing normal development of secondary sexual characteristics and a normal 46, XX karyotype. For this reason, MRKH syndrome usually remains undiagnosed until primary amenorrhea or difficulty in sexual intercourse occurs. In this study, a case of MRKH syndrome diagnosed in a child with idiopathic precocious puberty is reported.

Vaginal Reconstruction with Laparoscopic-perineal Rectosigmoid Colpopoiesis in Mayer-Rokitansky-Kuster-Hauser Syndrome: A Case Report

PURPOSE: Various operations have been proposed to compensate for congenital absence of the vagina using ileal or colonic interposition. These methods involve laparotomy, which shows postoperative complications such as long scar and delayed recovery. One case of neovagina reconstruction with laparoscopic rectosigmoid colpopoiesis in Mayer-Rokitansky-Kuster-Hauser syndrome is presented to avoid laparotomic complications. METHODS: Laparoscopic surgery was performed in a 27-year-old MRKH syndrome patient. After a cruciate incision, blunt dissection through two-finger wide space was created between the bladder and the rectum. A 14-cm rectosigmoid segment vascularized by a branch of sigmoid artery was isolated by laparoscopy. The distal end was sutured with vaginal vestibule mucosa. A continuity of intestine was restored by circular end-to-end proximate curved intraluminal stapler CDH29(R) through perineal opening. RESULTS: Total operation time was 4 hr 15 min. Normal walking and ingestion were possible within 3 days and 4 days after surgery. The hospital stay was 7 days and the patient was followed up for 6 months. The neovaginal introitus was wide enough for inserting two fingers, and there has been no narrowing of the neovagina on palpation as confirmed by vaginogram. The patient had functional self-lubricating neovagina without excessive mucous production or the need for routine dilation or unnoticeable scar. CONCLUSION: The successful result of this laparoscopic vaginal reconstruction technique with rectosigmoid segment suggests that this technique can be considered for the option of vaginal reconstruction in girls with the MRKH syndrome.

A Case of Mayer-Rokitansky-Kuster-Hauser (MRKH) Syndrome with Bilateral Gonadal Agenesis / 고신대학교의과대학학술지

Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by congenital aplasia of the uterus and the upper part of the vagina in women showing normal development of secondary sexual characteristics and a normal 46, XX karyotype. MRKH syndrome usually remains undetected until the patient presents with primary amenorrhea despite normal female sexual development. MRKH syndrome is the second frequent cause of primary amenorrhea. There have been several reports concerning gynecologic disease in MRKH syndrome, but there has been few case about MRKH syndrome with gonadal agenesis. We report an exceptional association between bilateral ovarian agenesis 46,XX and MRKH syndrome. A 27-year-old woman who presented with primary amenorrhea and absence of secondary sexual development. She had normal, 46XX karyotype, but no upper vagina, uterus and both ovary. And there was no urogenital and skeletal malformation. She was diagnosed as the atypical form of MRKH syndrome (bilateral gonadal agenesis 46 XX).

Clinical characteristics of women with Mullerian anomaly: Twenty years of experience at Asan Medical Center / 대한산부인과학회지

OBJECTIVE: To investigate the clinical characteristics and reproductive outcomes of women with Mullerian anomalies. METHODS: One hundred and eighty-six patients were diagnosed with Mullerian anomalies at the Asan Medical Center from 1990 to 2009 and their clinical characteristics and reproductive outcomes were analyzed. Mullerian anomalies were categorized according to the classification by the American Fertility Society (1988). RESULTS: Mullerian anomaly was noticed in 1 in 1,326 patients (0.075%). Most cases were found in adulthood (84.9%) whereas only 15.1% cases in adolescent or pediatric period. More than 40% of cases were asymptomatic and found incidentally but others suffered from amenorrhea (12.4%), dysmenorrhea (10.8%), abnormal menstruation (10.2%), etc. Most common type of uterine anomalies was uterine didelphys (30.6%), followed by bicornuate uterus (19.4%), Mayer-Rokitansky-Kuster-Hauser syndrome (10.8%), septate uterus (9.1%) and unicornuate uterus (8.6%). On the reproductive outcomes of 251 pregnancies identified, spontaneous miscarriages and preterm labor were quite common (55.8%), and the overall live birth rate was 48.6%. When each anomaly was individually analyzed, the live birth rate was 60.0% in the arcuate uterus and 58.0% in the uterine didelphys. The unicornuate and bicornuate uterus presented a similar chance of having a living child (42.1%, 46.7%), while the septate uterus showed a relatively lower live birth rate (32.4%). CONCLUSION: Although most cases of Mullerian anomalies are diagnosed in adulthood, many patients may suffer from menstrual abnormalities, dysmenorrhea or recurrent miscarriages since adolescence. The reproductive outcomes of the arcuate uterus and uterine didelphys were better, while those of septate uterus were poor in our study.

[ Effect of chick Embryonic Somites on Neural Rosette Formation in Mouse Embryonic Stem Cells]

The aim of the present study is to understand if EBs can generate neural rosette upon co-culture with chick embryo sornites. The mouse ES cells, line Royan Bi, were cultured in hanging drops to induce embryoid bodies [EBs] formation. Somites were isolated from the chick embryos and then embedded in alginate solution. Finally, alginate beads containing somites were co-cultured with EBs. RA was added to some EBs according to 2-12+12+ protocol Mean percentage of EBs containing early and late rosettes in somite, control and RA was 1456%, 2.6% and 0.0%, respectively and what is important to rosette formation in EBs was the preseice of neural inducing components as well as the time course of neural differentiation of EBs Chick embryonic somites can induce ES cells -derived EBs to generate rosttte structures with neuron formation capacity

Six cases of laparoscopic assisted neovaginoplasty using pelvic peritoneal flap in MRKH syndrome / 대한산부인과학회지

Vaginal agenesis is rare gynecologic condition, and the most common etiology is Mayer-Rokitansky-Kster-Hauser (MRKH) syndrome, characterized by the absence of uterus and vagina and presence of normal ovaries and tubes. In such patients, the evaluation for associated malformations as well as careful non-surgical and surgical approach are essential. The neovaginoplasty is an important issue for these patients in regard of functional and psychological standpoint. There are many options available for creation of neovagina. We report six cases of laparoscopic assisted neovaginoplasty using pelvic peritoneal flap.

La inervación sensitiva segmentaria dermatomas, miotomas y esclerotomas / The segmentary sensitive innervation: dermatomes, myotomes and sclerotomes

Los mapas de dermatomas, miotomas y esclerotomas son usados por los neurólogos y por los anestesiólogos regionalistas en su práctica clínica habitual. La determinación de la sensibilidad de las diferentes estructuras del cuerpo humano se inició en el siglo 19, continúa hasta nuestros días y en general los nuevos métodos empleados para la determinación de la sensibilidad han corroborado las investigaciones de los primitivos autores. Al analizar la historia de la confección de mapas de sensibilidad de piel, músculo y hueso encontramos a todas las grandes figuras de la Neurología involucradas de una u otra forma en la investigación de este tema fascinante y observamos como el ingenio, la investigación sistemática y también el análisis de enfermedades y malformaciones, que permiten objetivar dermatomas y esclerotomas de otra manera invisibles, han permitido avanzar cada vez más en la confección de estos mapas. Debe tenerse presente que todos los mapas de dermatomas están compuestos de muchas observaciones individuales, ya que en cada persona se determinan sólo unos pocos dermatomas. Por esta razón todos los mapas que muestran dermatomas para todo el cuerpo deben ser vistos como aproximaciones que no toman en cuenta las variaciones individuales. Además a pesar de que generalmente se asume el dermatoma como una definición anatómica los mapas en uso han sido determinados por métodos fisiológicos. Todo lo anterior unido al hecho que se han usado métodos diferentes por cada investigador puede explicar las variaciones que se observan entre diferentes autores.

MURCS association: a case report

MURCS association is a rare developmental disorder that affects females. The acronym MURCS stands for Mullerian, Renal, Cervicothoracic Somite abnormalities. It appears to occur randomly [sporadic] with a frequency of 1 in 50.000 females. In this paper, we present a two-year-old girl with typical features of this syndrome in association with right deviation of anorectal canal, subglottic stenosis and unilateral oblique inguinal hernia

MURCS association.

The MURCS association i.e. MUllerian duct aplasia, Renal aplasia, Cervicothoracic Somite dysplasia is a rare developmental disorder. The authors report a case of MURCS association with supernumerary ribs in a 7-month-old infant who presented with failure to thrive.

Influence of the neural tube/notochord complex on MyoD expression and cellular proliferation in chicken embryos

Important advances have been made in understanding the genetic processes that control skeletal muscle formation. Studies conducted on quails detected a delay in the myogenic program of animals selected for high growth rates. These studies have led to the hypothesis that a delay in myogenesis would allow somitic cells to proliferate longer and consequently increase the number of embryonic myoblasts. To test this hypothesis, recently segmented somites and part of the unsegmented paraxial mesoderm were separated from the neural tube/notochord complex in HH12 chicken embryos. In situ hybridization and competitive RT-PCR revealed that MyoD transcripts, which are responsible for myoblast determination, were absent in somites separated from neural tube/notochord (1.06 and 0.06 10-3 attomol MyoD/1 attomol á-actin for control and separated somites, respectively; P<0.01). However, reapproximation of these structures allowed MyoD to be expressed in somites. Cellular proliferation was analyzed by immunohistochemical detection of incorporated BrdU, a thymidine analogue. A smaller but not significant (P = 0.27) number of proliferating cells was observed in somites that had been separated from neural tube/notochord (27 and 18 for control and separated somites, respectively). These results confirm the influence of the axial structures on MyoD activation but do not support the hypothesis that in the absence of MyoD transcripts the cellular proliferation would be maintained for a longer period of time

Establishment of embryonic cultures and somatic embryogenesis in callus culture of guggul-Commiphora wightii (Arnott.) Bhandari.

Somatic embryogenesis in callus cultures of Commiphora wightii (Arnott.) Bhandari was achieved. Though the frequency of explants producing embryonic culture was low, immature zygotic embryos were the only suitable explants to produce embryonic callus after reciprocal transfers on media containing 2,4,5-trichlorophenoxy acetic acid (0.1 mgl(-1)) and kinetin (0.1 mgl(-1)) or devoid of growth regulators. All other media failed to produce embryonic callus. Embryonic cells were small, densely filled with cytoplasm and isodiametric as compared to non-embryonic cells, which were large, elongated and vacuolated. Maximum growth of embryonic callus was recorded on modified MS medium (MS-2 medium) supplemented with BA (0.25 mgl(-1)) and IBA (0.1 mgl(-1)). MS-2 salts supported higher growth of callus as compared to tissues grown on B5 medium containing same concentrations of plant growth regulators. Exogenous medium nutrients had no effect on somatic embryo development whereas plant growth regulators had little effect. Asynchronously growing embryos formed plantlets regularly which were successfully transferred to the field conditions.

Development of Model System for Radiation Induced Congenital Malformations by Whole Embryo Culture / 체질인류학회지

It is known that radiation can induce various kind of mutations, cancers and congenital malformations. Day 9 rats embryos were cultured by whole embryo culture method and irradiated 0.1, 0.5, 2 and 5 Gy at day 10 to study the effect of radiation on the development of rat embryos. Haversting after 48 hours culture, the morphological changes and apoptosis were investigated. In addition, we assessed the expression patterns of p53, WAF1, Bcl -2, Bcl -x and Bax. Compared to the control group, no remarkable morphological changes were observed in the low dosage group (0.1 and 0.5 Gy). But at high dosage group (2 and 5 Gy), growth was retarded and the heart beats were weak. The crown rump length, the number of somites, and branchial arch were decreased and the rotation of embryo and development of otic pit and lens pit, and upper limb bud was delayed significantly. Especially in the 5 Gy group the most of external morphology were difficult to discriminate. In histological observations, high dosage group showed marked increase in the number of apoptotic bodies in the optic cup, trigeminal ganglion, pharyngeal arches, heart and small intestine. In western blot analysis, Bcl -x and Bax were not expressed in all groups. Expression level of Bcl -2 was constant regardless of the amount of radiation. Expression level of p53 and WAF1 increased significantly in accordance with the increasing amount of radiation. Especially, WAF1 was expressed 7.2, 6.3, 9.9 and 11.3 folds more than the control groups when embryos were exposed to 0.1, 0.5, 2 and 5 Gy, respectively. Considering WAF1 arrests cell cycle, we concluded that cell cycle was affected most sensitively to radiation injury. From these results, radiation showed growth retardation, decrease in protein synthesis, increase in apoptosis and expression of related genetic materials. These results may be used as a standard to test the effect of drugs for reducing and protecting agents against deterious effect of radiation in developing embryo and fetus.

Re-closure Capacity of Surgically Induced Open Neural Tube Defect in Chick Embryos

OBJECTIVE: To determine whether there is a re-closure capacity of the open neural tube defect(ONTD) and to characterize its re-closing process, the morphological changes and the re-closure rate of a surgically induced ONTD are examined chronologically in early chick embryos. METHODS: Embryos of Hamburger and Hamilton stage 18-19 were used. The posterior roof of the central canal in the closed neural tube was incised longitudinally at the wing bud level. The incision was 3 somites long, which was equivalent to approximately 0.8mm. Following surgery, the embryos were re-incubated in ovo for three or five days. The area of the incision was observed with a stereomicroscope. Some of them were examined histologically with the transverse section of the wing bud area. They were divided into two groups(POD 3 and POD 5) according to the re-incubation period at the time of sacrifice and then into two subgroups(re-closure and defect group) according to the presence of ONTD at the operative site. RESULTS: The results showed : 1) Re-closure of ONTD occurred in 58%(23/40) of POD 3 embryos and 46%(22/48) of POD 5 embryos. The difference of re-closure was not statistically significant. 2) Most of the re-closed neural tubes revealed no significant difference from the controls in the histological examination. 3) In POD 3 and 5 groups, there was a tendency of zipper-like fusion in both re-closure and defect groups. CONCLUSION: The results of study showed that the neural tube of the early chick embryo has a re-closure capacity after being surgically reopened. Seemingly, re-closure occurs mainly before POD 3 and progresses from the ventral to the dorsal part of the neural tube. The mechanism of re-closure needs to be investigated further.

A Case of Klippel-Feil Syndrome

Klippel-Feil syndrome(KFS) consists of short neck, low posterior hairline and restriction of motion of the neck due to fusion of cervical vertebrae. The typical disorder results from a failure of the normal segmentation of mesodermal somites during 3-8 weeks of gestation. In 1912, the first complete clinical description of this syndrome was given by Klippel and Feil. Feil reported additional cases in 1919 and distinguished between three morphologic groups. The incidence of KFS has been estimated to be approximately 1 : 40,000-42,000 births. A slight female predilection has been noted. Although the disorder is sporadic, there are examples of familial occurrence; how ever, no clear mechanism of inheritance has been accepted. Since the disturbance producing a short neck occurs early in embryogenesis, defects in other organ systems may occur at the same time. Common musculoskeletal anomalies that accompany KFS include scoliosis, as well as Sprengel's deformity in as many as one-third of cases. Neurologic, cardiovascular, and urinary tract anomalies are associated with KPS. We report a case of Klippel-Feil syndrome with associates anomalies include Sprengel's deformity.

A simultaneous ex vivo model of embryogenesis: I. Organogenesis.

In vivo culture of chick embryo was carried out to develop an experimental interphase between in vitro and in vivo study of embryonic physiology. In the process, a simultaneous model of vasculogenesis and organogenesis has been worked out, which is impossible to achieve in mammalian system. Both early (40 hours of incubation) and late (64 & 88 hours of incubation) hours of cultures were conducted for morphological and morphometric studies. A new combination of stains was used in place of conventional haematoxylin and eosin in 40 hours old whole-mount of embryos. Semithin plastic sections were etched for haematoxylin/pyronin stain in addition to paraffin (both normal and enblock) sections. Specific stains (histological, enzyme histochemical or immunohistochemical) were chosen according to the specific organs/areas studied. Immunohistochemistry and NADPH-diaphorase activity were standardized in whole-mount of embryos. Morphometry was done using camera lucida and quantitative image analysis system. A parallel preparation of extra embryonic whole-mounts, paraffin and semithin plastic sections with different types of stainings provides evidence for the scope of the simultaneous study of vasculogenesis. Thus the morphological and morphometric data presented in this and the succeeding article describe the scope and avenues for the use of ex vivo model in various aspects of embryonic physiology, preliminary drug trials/metabolism, radiology, teratology and toxicology.