Expanding the phenotype of 22q11 deletion syndrome: the MURCS association

The MURCS association [Müllerian Duct aplasia or hypoplasia (M), unilateral renal agenesis (UR) and cervicothoracic somite dysplasia (CS)] manifests itself as Müllerian Duct aplasia or hypoplasia, unilateral renal agenesis and cervicothoracic somite dysplasia. We report on a 22-year-old woman with bicornuate uterus, right renal agenesis, C2-C3 vertebral fusion (MURCS association) and 22q11.2 deletion. Angio-MRI revealed the aberrant origin of arch arteries. Hashimoto thyroiditis, micropolycystic ovaries with a dermoid cyst in the right ovary and mild osteoporosis were also diagnosed. Accurate revision of radiographs enabled us also to identify thoracolumbar and lumbosacral vertebral-differentiation defects. Audiometry and echocardiogram were normal. Bone densitometry showed osteoporosis. As per our evaluation, the patient had short stature, obesity (BMI 30.7) and facial features suggestive of the 22q11 deletion syndrome. Multiplex ligation-dependent probe amplification analysis showed a de-novo 22q11.2 deletion confirmed by array-comparative genomic hybridization analysis. We discuss whether this is a casual association or whether it is an additional syndrome owing to the well known phenotype extensive variability of the 22q11 deletion 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.     

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.     

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.     

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.     

Vaginal agenesis, the hymen, and associated anomalies

Study ObjectivesReview anomalies in patients with vaginal agenesis. In particular, to clarify the impact of an absent hymen on the presence of other anomalies; on the success of creating a vagina with dilators; and on sexual function outcomes.DesignRetrospective medical record review; questionnaire on sexual function.SettingGynecology service at a children’s hospital and the practice of 1 gynecologist.ParticipantsAll patients with vaginal agenesis were identified from the databases, as well as the subgroup in which hymenal status was known.Outcome MeasuresData regarding hymen, renal, skeletal, cardiac, and other anomalies; for women who had a neovagina, the technique used to create a functional vagina.ResultsOf 69 females (age range 2–70 years), renal tract anomalies (43.3%), vertebral anomalies (29%), cardiac anomalies (14.5%), and syndromes including Klippel-Feil (7%) and MURCS association (7%) were identified. Where hymenal status was known (n = 47), 31 were normal, and 16 had an absent hymen. Where the hymen was absent, renal agenesis was increased (odds ratio = 13.5, P < .001). There was no association between other anomalies and an absent hymen, or between the various anomalies. For women without a hymen, the likelihood of failing dilation therapy was increased (odds ratio = 21.7; P < .01].ConclusionAn absent hymen makes renal agenesis more likely and increases the likelihood that dilator techniques will fail. This condition appears to be associated with reports of long-term problems with poor lubrication that are potentially related to the absence of the peri-hymenal Bartholin’s glands.     

ACOG Committee Opinion No. 355: Vaginal agenesis: diagnosis, management, and routine care

Vaginal agenesis occurs in 1 of every 4,000-10,000 females. The most common cause of vaginal agenesis is congenital absence of the uterus and vagina, which also is referred to as müllerian aplasia, müllerian agenesis, or Mayer-Rokitansky-Küster-Hauser syndrome. The condition usually can be successfully managed nonsurgically with the use of successive dilators if it is correctly diagnosed and the patient is sufficiently motivated. Besides correct diagnosis, effective management also includes evaluation for associated congenital renal or other anomalies and careful psychologic preparation of the patient before any treatment or intervention. If surgery is preferred, a number of approaches are available; the most common is the Abbe-McIndoe operation. Women who have a history of müllerian agenesis and have created a functional vagina require routine gynecologic care and can be considered in a similar category to that of women without a cervix and thus annual cytologic screening for cancer may be considered unnecessary in this population.     

ACOG Committee Opinion. Number 274, July 2002. Nonsurgical diagnosis and management of vaginal agenesis

Vaginal agenesis occurs once in every 4,000-10,000 females. The most common cause of vaginal agenesis is congenital absence of the uterus and vagina, which is also referred to as müllerian aplasia, müllerian agenesis, or Mayer-Rokitansky-Küster-Hauser syndrome. The condition usually can be managed nonsurgically with the use of successive dilators if it is correctly diagnosed and the patient is sufficiently motivated. Besides correct diagnosis, effective management also includes evaluation for associated congenital, renal, or other anomalies and careful psychologic preparation of the patient before any treatment or intervention. If surgery is preferred, a number of approaches are available; the most common is the Abbe-McIndoe operation.     

Creation of a neovagina with use of a pudendal thigh fasciocutaneous flap and restoration of uterovaginal continuity

OBJECTIVE: To create a neovagina and an endocervival canal in two patients with vaginal aplasia and a functioning uterus. DESIGN: Technique and instrumentations. SETTING: University hospital. PATIENT(S): A 31-year-old woman with vaginal aplasia and a double noncommunicating uterus (classified as Mayer-Rokitansky-Kuster-Hauser syndrome) and a 19-year-old woman with partial vaginal aplasia and a functional uterus. INTERVENTION(S): Creation of a neovagina by using the bilateral pudendal thigh fasciocutaneous flap procedure and laparotomy to establish uterovaginal continuity. MAIN OUTCOME MEASURE(S): Clinical follow-up evaluation of restoration of outflow of menstrual blood and coital satisfaction. RESULT(S): Uterovaginal continuity was established in both patients, resulting in normal menstruation. Granulomatous polyps occurred in one patient, and stenosis at the site of anastomosis occurred in the other patient; these conditions were successfully managed. Unimpeded menstrual flow continued after 1 year of follow-up in one patient and 3 years of follow-up in the other patient. CONCLUSION(S): Bilateral fasciocutaneous pudendal thigh flaps permit vaginal reconstruction and a uterovaginal connection in patients with vaginal agenesis and a functional uterus. The main advantages of this technique are that postoperative dilatation is not necessary, sensation is maintained, and the resulting scar is inconspicuous. The main disadvantage is the presence of some sebaceous vaginal secretion and hair in the vaginal lining; the latter can be managed by preoperative and postoperative laser depilation.     

VACTERL association with hydrocephalus in a fetus conceived by in vitro fertilization and embryo transfer

ObjectiveWe present a case of VACTERL association with hydrocephalus (VACTERL-H) in a fetus conceived by in vitro fertilization (IVF) and embryo transfer (ET) and review the literature.Case reportA 35-year-old woman presented with multiple fetal anomalies at 22 weeks of gestation. She and her husband were non-consanguineous and there was no family history of congenital malformations. This was her second pregnancy conceived via IVF-ET. Two embryos had been implanted and only one survived. She underwent chorionic villus sampling at 17 weeks of gestation because of oligohydramnios and advanced maternal age. Cytogenetic analysis revealed a karyotype of 46,XY, and array comparative genomic hybridization analysis revealed no genomic imbalance. Prenatal ultrasound at 21 weeks of gestation revealed a singleton with fetal biometry equivalent to 18 weeks, ventriculomegaly, a small cerebellum, and a ventricular septal defect. Level II ultrasound showed a single umbilical artery, scoliosis, a right club hand, radial aplasia, and renal agenesis. The parents elected to terminate the pregnancy at 22 weeks of gestation, and a fetus was delivered with bilateral arthrogryposis, right radial aplasia, a club hand and thumb aplasia, hypoplasia of the left thumb, scoliosis, and an imperforate anus. The clinical findings were consistent with the diagnosis of VACTERL-H. Molecular analysis of PTEN, FANCB, and HOXD13 genes revealed no mutation.ConclusionPrenatal diagnosis of radial ray defects in fetuses conceived by assisted reproductive technology should include a differential diagnosis of VACTERL association with anorectal malformation. VACTERL-H may occur in pregnancy after IVF-ET.     

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.     

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.     

Tetralogy of Fallot,imperforate anus,and Müllerian,renal, and cervical spine (MURCS) anomalies in a 15-year-old girl

STUDY OBJECTIVE: To examine the etiology of MURCs anomalies and the management of a patient with these anomalies as well as cardiac and anorectal abnormalities causing primary amenorrhea and abdominal pain. DESIGN: Case study. RESULT: Relief of pelvic pain following GnRH agonist therapy and continuous oral contraceptives. CONCLUSION: MURCS (Müllerian, Renal, Cervical Spine) is a well-described grouping of multi-organ, nonlethal abnormalities that are infrequently detected in women with menstrual abnormalities. The association of MURCS with cardiac and anorectal abnormalities may be one of coincidence or may indicate that the abnormalities share common genetic or environmental (cellular or microbiologic) etiologies.     

Successful Pregnancy Following Surgery in the Obstructed Uterus in a Uterus Didelphys with Unilateral Distal Vaginal Agenesis and Ipsilateral Renal Agenesis: Case Report and Literature Review

SynopsisAfter surgical correction of unilateral distal vaginal agenesis, the obstructed didelphic uterus was able to harbor 2 subsequent pregnancies.BackgroundThere was a congenital anomaly syndrome of uterus didelphys, unilateral distal vaginal aplasia, and ipsilateral renal aplasia. Intuition suggests that later pregnancy would be in the unobstructed uterus.ObjectiveThe purpose is to report pregnancy occurring twice in a previously obstructed didelphic uterus after surgical correction.CaseA girl aged 13 years, 8 months presented with the syndrome of didelphic uterus, upper right hematocolpos, and right renal aplasia. Right vaginal marsupialization was done. Subsequently, she had 2 pregnancies in the right didelphic uterus.ConclusionPregnancy occurred in the obstructed uterus despite a large hematometra, extensive right pelvic peritoneal endometriosis, and hematocolpos. The surgeon should make every effort to preserve the obstructed uterus.     

Sexual delusion in a case of vaginal aplasia after surgical operation for neovagina

The Mayer-Rokitansky-Kuster-Hauser (MRKH) is a syndrome of unknown etiology characterized by congenital aplasia of the uterus and the upper part (2/3) of the vagina in women showing normal development of secondary sexual characteristics. We report the case of a patient with vaginal aplasia and schizophrenia presenting with sexual delusion. To the authors' knowledge this is the first case to provide evidence of coexistence between MRKH and sexual delusion in a schizophrenic patient. The core of the patient's delirium was that she was having sexual intercourse with an eminent person through the big toe of her right foot. We approached this case using a neurological and a psychodynamic hypothesis. The neurological hypothesis suggests that the "deactivation" of the patient's genitalia led to an expansion of the adjacent big toe cortical area. The psychodynamic hypothesis supports that the sexual function and pleasure was partially expelled from the body image and was stored in a non sexual part of the body (i.e., big toe). Clinicians should be aware of this association and offer patients with MRKH psychological or/and psychiatric evaluation.     

Lung agenesis in a neonate presenting with contralateral mediastinal shift.

A neonate with right lung agenesis presenting with respiratory distress is described. The unusual radiological features were contralateral mediastinal shift (in contrast to expected ipsilateral shift) and diaphragmatic eventration on the affected side. Mediastinal shift to the opposite side was due to intrathoracic hepatic herniation under a high placed eventrated diaphragm. Both these features have not been reported in association with lung agenesis to date. The authors have discussed other causes of respiratory distress in newborns that can cause mediastinal shift and have urged a high degree of clinical suspicion to pick up the cases with lung agenesis. The newer diagnostic modalities and the causes of mortality in neonates with this anomaly have also been highlighted.     

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.     

Surgical correction of vaginal anomalies

Summary of accurate diagnosis and surgical management of vaginal anomalies. Imperforate hymen, transverse septa, and distal vaginal agenesis present similarly with pain and hematocolpos. Likewise, imperforate hymen, transverse septa, distal vaginal agenesis, and Müllerian aplasia may appear similarly on examination. Imaging should be used to better differentiate the anomaly. Although surgical correction is the mainstay of hymenal anomalies, septa, obstructed hemivaginas, and distal vaginal agenesis, first-line therapy for Müllerian aplasia is progressive dilation. Many surgical techniques are also described but no consensus exists as to the best one. Clinicians should be aware of the appropriate evaluation, differential diagnosis, and management options available for vaginal anomalies.     

VATER--tibia aplasia association: report on two patients

We report two patients with oesophageal atresia, tracheo-oesophageal fistula and unilateral tibial aplasia. The karyotype in both patients was normal and both cases were sporadic. The congenital defects of the children can be regarded as an uncommon variant of VA(C)TER(L) association. Recently Basel and Goldblatt [(2000) Clin Dysmorphol 9:205-208] reported a similar patient with a VATER-tibia aplasia association.