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.     

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.     

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.     

Antenatal evaluation of an encephalocele in a dizygotic twin pregnancy using fast magnetic resonance imaging

We report a case of an encephalocele in a dizygotic twin pregnancy, following ovulatory induction. In the involved fetus, an abnormal shadow like an encapsulated-solid tumor located on the occiput was found by routine maternal transabdominal ultrasonography at 17 weeks of gestation. The parents did not accept induced abortion because of the presence of another fetus with no abnormality on ultrasonography. At 35 weeks of gestation, transabdominal ultrasound examination showed a large occipital cyst, composed of protrusive fetal brain and cerebrospinal fluid. Fast-scanning magnetic resonance imaging delineated more clearly the inside of the abnormal lesion and thus allowed confirmation of the putative diagnosis of fetal encephalocele during pregnancy. Surgical report was possible in this case, and the patient had no severe physical or neurological abnormalities 10 months after birth. Since the prognosis appears to depend primarily on how prominent the brain tissue is inside the herniated sac, this approach had benefit for clinical decision making.     

Mosaic trisomy 11 in a fetus with bilateral renal agenesis: co-incidence or new association?

We report a fetus with mosaic trisomy 11 who also had bilateral renal agenesis. We describe the post-mortem examination findings in the fetus and cytogenetic analysis. There are no earlier reports of full trisomy 11, presumably because it is lethal and results in early spontaneous miscarriages. There is only one report published earlier in a fetus with mosaic trisomy 11. There have been a few case reports of trisomy 11 identified in pre-natal samples, where it was associated with normal outcome. Bilateral renal agenesis has not been reported earlier in association with mosaic nor non-mosaic trisomy 11. We describe this rare cytogenetic finding in a fetus with bilateral renal agenesis. We also discuss the issues around genetic counselling when this is encountered in clinical practice.     

Prenatal diagnosis of fetal exencephaly associated with amniotic band sequence at 17 weeks of gestation by fetal magnetic resonance imaging

We report a fetus with exencephaly diagnosed by fetal magnetic resonance imaging (MRI) at 17 weeks of gestation. Fetal ultrasound performed at 13 and 17 weeks of gestation suggested occipital encephalocele. However, the fetal MRI done at 17 weeks of gestation showed exencephaly and suggested amniotic bands as the cause. By providing early and precise information regarding the abnormality and the possible etiology, the fetal MRI enabled us to provide the couple and their families with accurate information regarding the low recurrence risk of this condition.     

Prenatal diagnosis of dyssegmental dysplasia. A case report

BACKGROUND: Since the first use of sonography, most fetal dwarfism has been detectable prenatally. The correct differentiation of the subtype of dwarfism is difficult at times. Dyssegmental dysplasia is probably an exception to these subtypes because the vertebral disorganization and occipital encephalocele at times permits prenatal diagnosis. CASE: A 34-year-old woman, gravida 3, para 1, elective abortion 1 for dwarfism, was referred at 27 weeks' gestation for cystic hygroma. Further sonographic findings included: cystic hygroma with massive ascites, micromelia, occipital encephalocele, spinal disorganization and hydramnios. The fetus and both parents appeared to have a normal karyotype. Later the pregnancy was terminated with vaginal delivery. The fetus had micromelia, camptomelia, cystic hygroma, a flat face, short neck, short trunk, narrow thorax with protuberant abdomen, scoliosis and clubfeet. CONCLUSION: Sonography is effective in prenatal diagnosis of dyssegmental dysplasia. With sonography, diagnosis of dyssegmental dysplasia becomes possible as early as the first trimester.     

Prenatal morphology in Meckel's syndrome

Prenatal morphology of Meckel's syndrome was studied in five fetuses of different gestational age, that had been aborted because ultrasonography and elevated amniotic AFP-levels indicated neural tube defect. Histologically, the enlarged polycystic kidneys were completely alike with respect to the type of involvement and differed only in the severity of changes. They could be identified at type III cystic kidneys according to the classification of Potter. Proliferation of hepatic bile ducts and slight cystic dilatation of pancreatic ducts is already evident in the youngest fetus. Additional cyst formation in the epididymis was found in one of the cases. Occipital encephalocele, located within an apical occipital bone defect was always associated with a second mostly occult encephalocele protruding through a separated defect of the basal occipital squame and of the first and second vertebral arch. It is assumed that double encephalocele represents a constant finding in Meckel's syndrome, indicating a specific pattern within the disturbance of neural tube closure.     

Prenatal Diagnosis of Meckel–Gruber Syndrome in a Pregnancy Obtained With ICSI

The association of occipital encephalocele, cleft palate, postaxial polydactyly, polycystic kidneys, and hepatic cysts is well known as Meckel–Gruber syndrome (MGS). Nowadays, the diagnosis of MGS is usually performed prenatally by ultrasound findings. MGS was previously described following in vitro fertilization. We report a case of MGS diagnosed at 17 weeks in a pregnancy obtained with intra-cytoplasmic sperm injection (ICSI).     

Antenatal sonographic findings of right pulmonary agenesis with ipsilateral microtia: a possible new laterality association

Right pulmonary agenesis is a rare congenital malformation which results in secondary dextrocardia in situs solitus. Ipsilateral microtia in this context composes a laterality syndrome. The prenatal sonographic findings of this abnormality have not been previously reported. We describe the association of dextrocardia in situs solitus, intact diaphragm and right microtia. This was sonographically diagnosed at mid-gestation in an euploid fetus. Surgical evacuation of the pregnancy confirmed the external malformation. Laterality association should be assessed in a fetus with sonographic findings of pulmonary agenesis. The differential diagnosis and updated literature review is presented.     

Syndromic encephalocele in a fetal case with a 1p35-pter deletion and a 14q32-qter duplication inherited from a maternal balanced translocation

Occipital encephalocele belongs to the family of neural tube defects, which occur in one among 2000 to 5000 live births. Syndromic encephaloceles include Meckel-Gruber syndrome and various chromosomal abnormalities. We report on a fetal case (13 WG) with bilateral cleft lip and palate, choanal atresia, occipital encephalocele, bilateral club feet, bilateral multicystic kidneys, enlarged bladder and urethral atresia. The fetal chromosome analysis showed a maternally inherited unbalanced translocation between the short arm of chromosome 1 and the long arm of chromosome 14, resulting in 1p35-pter deletion and 14q32-qter duplication (46,XY,der(1),t(1;14)(p35;q32)). Since the chromosomal breakpoints have not previously been implicated in syndromic encephalocele, this observation is of interest for the identification of other genes responsible for occipital encephalocele.     

MRI diagnosis of occipital cephalohematoma mimicking an encephalocele

A 4-day old neonate presented with a midline swelling located on the back of its head. The two most likely causes of the swelling were cephalohematoma, which is self-limiting and carries a benign prognosis, and encephalocele, often associated with central nervous system malformations. Evaluation with magnetic resonance imaging (MRI) revealed a subperiosteal blood collection with intact underlying structures, establishing the diagnosis of a cephalohematoma. This is the first report to show the value of MRI in distinguishing between an occipital cephalohematoma and an encephalocele.     

The BOR syndrome and renal agenesis--prenatal diagnosis and further clinical delineation

This is the first report of prenatal diagnosis of a fetus with brachio-oto-renal dysplasia (BOR) syndrome with right-sided renal agenesis and severe left hypoplasia. The father of this fetus had malformed external ears, a left-sided preauricular pit and branchial cyst, and bilateral mild to moderate deafness without a demonstrable renal anomaly. This family highlights the variable expressivity seen in the autosomal dominant BOR syndrome, the importance of genetic counselling for families with BOR syndrome, and the aetiologic heterogeneity of renal agenesis.     

Familial orofaciodigital syndrome type I revealed by ultrasound prenatal diagnosis of porencephaly.

Porencephaly is a rare central nervous system (CNS) abnormality that can be caused by an intraparenchymal destructive process or a developmental defect. Here we report on a prenatal ultrasound diagnosis of complex CNS abnormalities including agenesis of the corpus callosum, agenesis of the cerebellar vermis, bilateral hydrocephaly, and bilateral porencephaly in fetus at 33 weeks' gestation. The diagnosis of familial orofaciodigital syndrome type I (OFD I) was raised after fetal autopsy, clinical examination of the family, and the X-linked dominant inheritance pattern. This is the fourth report of porencephaly in association with OFD I. We discuss the difficulties in genetic counselling since OFD I shows variable expressivity of the phenotypic features. Furthermore, we emphasize the importance of a detailed ultrasound examination after a prenatal diagnosis of porencephaly.     

Concordant occipital encephalocele in monoamniotic twins

Anomalies occur with a greater frequency in twin gestations. Due to its multifactorial inheritance, twins are usually discordant for encephalocele. We present a case of monoamniotic twins concordant for occipital encephalocele and discordant for lung and cord anomalies.Ultrasonographic examination at 17 weeks' gestation revealed occipital encephalocele in both fetuses. The maternal serum level of alpha-fetoprotein was increased. Fetal autopsy revealed occipital encepaholocele in both twins and right pulmonary hypoplasia and one umbilical artery in one sibling. Monoamniotic twins concordant for encephalocele occur with extreme rarity. To the best of our knowledge, monoamniotic twins concordant for this neural tube defect have not been previously reported.     

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.     

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.     

Prenatal diagnosis of occipital encephalocele,mega-cisterna magna,mesomelic shortening,and clubfeet associated with pure tetrasomy 20p

We present the first case of a fetus with pure tetrasomy 20p proven by cord-blood sampling at 24 weeks of gestation. This case was diagnosed in utero with multiple congenital anomalies including occipital encephalocele, mega-cisterna magna, mesomelic shortening, and clubfeet. An analysis of GTG-banded chromosomes of 20 metaphase cells was performed. Female karyotype [47,XX, +i(20)(p10)] was revealed in all cells. Pure tetrasomy 20p was confirmed using fluorescent in situ hybridization (FISH) with a telomere probe for chromosome 20p in all seven metaphase cells. The pregnancy was terminated because of associated multiple anomalies and severe oligohydramnios. The postmortem examination confirmed the prenatal diagnosis.     

Prenatal diagnosis of septal agenesis with normal pituitary function

Septal agenesis is a rare brain malformation that is characterized by partial or complete absence of the septum pellucidum, either isolated or associated with other brain anomalies. We report a case presenting with septal agenesis and normal optic chiasm and pituitary function in a fetus at 19 weeks of gestation.     

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.