MURCS and thenar hypoplasia

We describe the case of a woman with some features of the MURCS (Müllerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia) association, along with a radial ray anomaly. She had fusion of two cervical vertebrae, and a unicornuate uterus as MURCS components; and thenar muscle hypoplasia and absent radial pulses reflecting radial ray elements. We review two similar cases from the literature. We discuss whether our case might represent an incomplete and variant form of the MURCS association, or an example of an overlap between the MURCS and VATER (vertebral, anal, tracheo-esophageal, radial) associations.     

Endocrine evaluation in a patient with MURCS association and ovarian agenesis

A new case of Mullerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia (MURCS association) in a 16-yr-old female patient is reported. In addition, agenesis of the right ovary plus hypoplasia of the right craniofacial bones were also present. Dynamic tests of anterior pituitary reserve (LH-RH, TRH and hypoglycemia) showed normal responsiveness of this gland in terms of LH, FSH, TSH, prolactin and growth hormone secretion, whilst a subnormal plasma cortisol response to hypoglycemia and exogenous ACTH (in the presence of unilateral adrenal agenesis) was found. Functional integrity of the hypothalamic-pituitary-ovarian axis was also documented. The presence of two additional and previously unreported congenital anomalies in this patient with MURCS association underlines the wide spectrum of the syndrome.     

Müllerian Agenesis in Cat Eye Syndrome and 22q11 Chromosome Abnormalities: A Case Report and Literature Review

Background

Although Müllerian agenesis is the second most common cause of primary amenorrhea the underlying etiology in most cases is unknown. Müllerian agenesis has been reported as a rare finding associated with chromosomal aberrations of the 22q11 chromosomal region including at least 1 individual with cat eye syndrome (CES) and 10 individuals with deletions or duplications of the 22q11.2 region. However, a potential link between 22q11 abnormalities and uterine malformations has been difficult to adequately ascertain because of the limited case reports in the literature.

A patient with Mullerian abnormalities, renal dysplasia, cervical spine fusion, cataracts and intellectual disability: MURCS-plus?

We report a 15-year-old girl with features of the MURCS (Mullerian abnormalities, renal agenesis/ectopy and cervicothoracic somite dysplasia) association and birth defects not typically associated with MURCS. In addition to seizures and intellectual disability, she has cortical brain heterotopia, bilateral subclinical cataracts, submucous cleft palate and patent ductus arteriosus. We propose that this patient represents a more severe form of MURCS, or 'MURCS-plus', which may represent a defect of or insult to mesodermal morphogenesis.     

Rokitansky-Küster-Hauser syndrome with ectrodactyly

This paper describes an 18-year-old patient with Rokitansky-Küster-Hauser (R-K-H) syndrome. In this case, apart from the usual alterations associated with the R-K-H syndrome, such as aplasia of the Müllerian ducts, renal agenesis, ectopic kidney and anomalies of vertebral column, ribs and hips, rare skeletal, unilateral abnormalities of the left hand and foot were present, such as ectrodactyly. This malformation, seen in prepubertal age, had led to an incorrect diagnosis of acrorenal syndrome.     

Mayer-Rokitansky-Küster-Hauser syndrome associated with unilateral gonadal agenesis. A case report

BACKGROUND: Mayer-Rokitansky-Küster-Hauser syndrome is the second most frequent cause of primary amenorrhea, with a reported incidence of 0.002%. Patients have a normal karyo-type and usually normal ovaries. Associated ovarian abnormalities are rarely reported. CASE: A 17-year-old woman with primary amenorrhea was evaluated by diagnostic laparoscopy, which showed complete müllerian agenesis. On the left side, the uterine tube and round ligament were hypoplastic, and the ovary was absent. The karyotype was 46, XX. Intravenous urography revealed a right kidney below the normal site with malrotation abnormality. CONCLUSION: Müllerian duct agenesis coexisting with unilateral ovarian agenesis and a contralateral renal abnormality has not been widely described before. Unilaterality might play a role in the etiologic factor of Mayer-Rokitansky-Küster-Hauser syndrome.     

Mullerian agenesis and thrombocytopenia absent radius syndrome: a case report and review of syndromes associated with Mullerian agenesis

Mullerian agenesis, commonly referred to as Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS), is a congenital defect that is most commonly associated with renal and spinal malformations. It is very rare for Mullerian agenesis to be accompanied by malformations of the extremities. In this report, we describe a 22-year-old woman with Mullerian agenesis and thrombocytopenia absent radius syndrome (TARS). We also review rare syndromes associated with Mullerian anomalies, including Mullerian hypoplasia/aplasia-renal agenesis-cervicothoracic somite dysplasia (MURCS), Roberts syndrome, Bardet-Biedl syndrome (BBS), McKusick-Kaufman syndrome (MKS), Wolf-Hirschhorn syndrome, and others. The pathogenesis of these complex malformation syndromes is not well understood as a result of their sporadic occurrence. However, some of these syndromes do follow a pattern of inheritance, suggesting that they could provide insights into our understanding of their origins. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader should be able to review the rare congenital defects associated with Mullerian agenesis, to determine the genetic etiologies of the associated syndromes with Mullerian agenesis, and to discuss information for parental counseling related to inheritance patterns and growth and development of the affected child.     

Hemifacial microsomia,external auditory canal atresia,deafness and Mullerian anomalies associated with acro-osteolysis: a new autosomal recessive syndrome?

We report the combination of hemifacial microsomia, external auditory canal atresia, deafness and acro-osteolysis in several members of a highly consanguineous Asian family. In addition Mullerian anomalies have been found in two female members of the family. The external auditory canal stenosis and Mullerian anomalies in this family are similar to those reported by Winter et al. [(1968) J Pediatr 72 : 88-93] and overlap with those found in Goldenhar syndrome and Mullerian duct/renal aplasia/cervicothoracic somite dysplasia (MURCS), CHARGE and VATER associations. However, to the authors' knowledge, acro-osteolysis has not been reported in patients with any of these conditions. Overall, the findings in this family appear to be unique and the presence of consanguinity suggests an autosomal recessive condition with variable expression.     

MURCS association: case report

Clinical term of association refers to a not randomized congenital malformations which are present in one single subject. The term MURCS is an acronym for (MU) Mullerian, (R) Renal, (C) Cervicothoracic, (S) Somite abnormalities. We communicate a case of a phenotipically normal 16 years old female patient with primary amenorrhea due to müllerian malformations and cervicothoracic dysplasia integrating the MURCS association diagnosis.     

Double uterus with an obstructed hemivagina and ipsilateral renal agenesis: report of 5 cases and a review of the literature.

Maldevelopment of the Müllerian duct system can result in various uterine, vaginal, and renal abnormalities. Complete or partial absence of Müllerian duct fusion and/or canalization results in a septate, bicornuate or didelphys uterus with various types of hemivaginal obstruction. In addition, unilateral renal agenesis is a common association. Five patients with uterine anomalies and an obstructed hemivagina are described according to the complete or incomplete obstruction between the double vagina and uterus. Early and accurate diagnosis is important, but difficult, due to the variable clinical pictures. Sonographic evaluation can provide valuable diagnostic information. Early diagnosis and excision of the obstructed vaginal septum can completely relieve the symptoms and prevent further sequelae.     

Müllerian aplasia associated with maternal deficiency of galactose-1-phosphate uridyl transferase

The activity and electrophoretic pattern of galactose-1-phosphate uridyl transferase (transferase), a key enzyme in galactose metabolism, were analyzed in four patients with Müllerian aplasia (Rokitansky-Küster-Hauser syndrome) and their mothers. Mothers of two of the patients had genetic variations of their transferase enzymes with activities below the normal range. Affected daughters from these two mothers also had genetic variations of the transferase enzyme. In one of the patients whose Müllerian aplasia had been diagnosed 15 years previously, premature ovarian failure developed. These case reports suggest a possible association between errors of galactose metabolism, Müllerian aplasia, and premature menopause--an association that is supported by a rodent model in which female offspring of mothers fed a high-galactose diet were born with reduced oocyte numbers and delayed vaginal opening.     

Molecular analysis of the anti-Müllerian hormone,the anti-Müllerian hormone receptor,and galactose-1-phosphate uridyl transferase genes in patients with the Mayer-Rokitansky-Küster-Hauser syndrome

Introduction. Müllerian agenesis, also named the Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) or vaginal aplasia, is the second most common cause of primary amenorrhea. It is characterized by the congenital absence of the Müllerian structures including the Fallopian tubes, the uterus, and the internal portion of the vagina in an otherwise normally feminized 46,XX subject. Most cases are sporadic in inheritance, but the occurrence of some patients with chromosomal translocations or even familial aggregates suggest a genetic basis for the disease, although the etiology of the disease is still unknown. It has been suggested that activating mutations in the anti-Müllerian hormone (AMH) or in its receptor (AMHRII) are potential sources for the defect. Methods. In this study we describe the molecular analysis of both the AMH and AMHR genes in a group of 15 patients with Müllerian agenesis. After sequencing all exons and exon/intron junctions of both genes, we were not able to detect any deleterious mutation. Results. Five new polymorphisms, 2 of them in the AMHRII gene and 3 of them in the AMH gene, were identified. No significant differences between patients and controls were observed in the frequency of a given polymorphism. Conclusion. This work reinforces the view that molecular defects in the AMH or AMHR are unlikely sources for the MRKHS syndrome.     

Prenatal diagnosis of familial 22q11.2 deletion syndrome in a pregnancy with concomitant cardiac and urinary tract abnormalities in the fetus and the mother

ObjectiveWe present prenatal diagnosis of familial 22q11.2 deletion syndrome in a pregnancy with concomitant cardiac and urinary tract abnormalities in the fetus and the mother.Case reportA 28-year-old woman primigravid underwent amniocentesis at 23 weeks of gestation because of fetal ultrasound findings of aortic stenosis, interrupted aortic arch (IAA), left multicystic kidney, right hydronephrosis and ureterocele. Amniocentesis revealed a karyotype of 46,XX. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr 22q11.21 (18,894,835-21,505,417) × 1.0 [GRCh37 (hg19)] with a 2.611-Mb 22q11.21 deletion encompassing 41 Online Mendelian Inheritance in Man (OMIM) genes including UFD1L, TBX1, GNB1L, COMT and MED15. aCGH analysis on the DNAs extracted from parental bloods confirmed that the mother carried the same 22q11.21 microdeletion. Level II ultrasound additionally found ventricular septal defect (VSD) and persistent left superior vena cava (PLSVC). Examination of the woman showed short stature, malar hypoplasia, hypertelorism, bulbous nasal tip, prominent nasal root, hypoplasia of nasal wings, right renal agenesis, left ureterovesical reflux and VSD with repair, but normal intelligence and normal neuropsychiatric development. The woman decided to continue the pregnancy, and a 2903-g female baby was delivered at 38 weeks of gestation with left multicystic kidney, right hydronephrosis, dysgenesis of corpus callosum, IAA, VSD, PLSVC, patent ductus arteriosus, patent foramen ovale, atrial septal defect, dilated main pulmonary artery and tricuspid regurgitation. The neonate died at the age of one month.ConclusionPrenatal diagnosis of concomitant congenital heart defects and urinary tract abnormalities in the fetus and the parent should raise a suspicion of familial 22q11.2 deletion syndrome.     

Persistent fifth aortic arch associated with 22q11.2 deletion syndrome.

BACKGROUND: Chromosome 22q11.2 deletion is frequently associated with conotruncal malformations and aortic arch anomalies. This study investigated the association of chromosome 22q11.2 deletion with clinical manifestations in four pediatric patients with persistent fifth aortic arch. METHODS: Four patients with persistent fifth aortic arch treated between July 1997 and June 2004 were included in this retrospective study. There were two girls and two boys, aged 2 days to 11.3 years, with persistent fifth aortic arch and cardiac conotruncal malformations. Chart recordings, plain chest films, two-dimensional and Doppler echocardiograms, cardiac catheterization with angiograms, surgical findings, and cytogenetic study were analyzed. RESULTS: Clinically, all four patients had the cardinal phenotypic features of 22q11.2 deletion syndrome, including cardiovascular malformations (conotruncal malformations and aortic arch anomalies), abnormal facies, thymic hypoplasia, canopy anomaly of the palate (high-arched palate, rather than cleft palate), and hypocalcemia (or hypoparathyroidism). All four patients were confirmed to have chromosome 22q11.2 deletion. CONCLUSION: Congenital conotruncal malformations, including tetralogy of Fallot with pulmonary atresia or stenosis, and aortic arch anomalies including a persistent fifth aortic arch or a right aortic arch, should lead to suspicion of chromosome 22q11.2 deletion when manifested together with any one of the other four cardinal phenotypic features.     

Müllerian tract abnormalities and associated auditory defects.

Fifteen women with müllerian defects and a control population of 15 with normal müllerian systems underwent dynamic audiometric testing. The rate of auditory defects in women with müllerian abnormalities (33%) was significantly higher (P less than .05) than in the control population (0%). Those patients manifested mild, moderate and severe sensorineural defects in the high-frequency range. The defects were not accounted for by age or occupation and were associated with renal agenesis in 60% of the cases. One patient with normal audiometric testing and a septate uterus had a family history significant for an identical twin sister with unilateral renal agenesis, ipsilateral congenital deafness and an unevaluated müllerian tract. The results of the study suggest that a spectrum of auditory changes may exist in association with müllerian defects, ranging from previously described congenital deafness to more subtle hearing defects not clinically evident.     

Obstructive Müllerian Anomalies in Menstruating Adolescent Girls: A Report of 22 Cases

Study Objective

To assess the clinical course of obstructive Müllerian anomalies found in girls after menarche.

Atypical mucinous metaplasia and intraepithelial neoplasia of the female genital tract—a case report and review of the literature

Müllerian metaplasia of the female genital tract is usually of limited extent and subtype. We describe the replacement of the lining of the entire genital tract and much of the overlying pelvic serosa by metaplastic müllerian epithelium, in a nulliparous 65-year-old woman with cervical agenesis. She did not have Peutz-Jeghers syndrome and had not had any form of prior hormonal treatment. The metaplastic epithelium extended from the vagina to the serosal surface of the pelvic organs. Mucinous epithelium predominated. In addition, there was multifocal dysplasia of the metaplastic epithelium; this was most prominent in the fallopian tubes where there was marked papillation with cytoarchitectural features reminiscent of a borderline mucinous ovarian tumor. Although müllerian metaplasia is well recognized at different sites within the female genital tract, this highly unusual finding of multiple metaplastic epithelial subtypes and dysplasia involving the mucinous metaplastic epithelium along the entire genital tract and pelvic serosal surface has not, to the best of our knowledge, been reported previously in the absence of Peutz-Jeghers syndrome.     

MURCS association with encephalocele: report of a second case

We report a female fetus with occipital encephalocele, dysraphism of the cervical spine, right renal agenesis and Mullerian agenesis. Additional findings included posterior cleft palate, absent left umbilical artery and Meckel's diverticulum. This fetus had the features of MURCS association with occipital encephalocele. This is the second report of encephalocele with MURCS association.     

Uterus didelphys with unilateral obstructed hemivagina and renal agenesis on the same side.

A rare condition, complete or incomplete duplication of uterus and cervix with unilateral vaginal obstruction, is usually associated with ipsilateral renal agenesis. In such kinds of Müllerian and Wolffian duct anomalies as the one reported here with accumulation of menstrual blood in the obstructed vagina, the patient usually complains of a pelvic mass and associated severe and increasing dysmenorrhea. A case, diagnosed and treated at our Department, is presented.