Prenatal diagnosis of megacystis-microcolon-intestinal hypoperistalsis syndrome: contribution of amniotic fluid digestive enzyme assay and fetal urinalysis

OBJECTIVES: Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a usually lethal disease during the first year of life. There is no specific ultrasound prenatal diagnosis and no identified genetic locus. The value of amniotic fluid digestive enzyme assay and fetal urine biochemistry in the prediction of MMIHS was analysed. METHODS: Retrospective study of 14 MMIHS cases. Amniotic fluid digestive enzymes and fetal urine biochemistry were compared in MMIHS and megabladder (63 and 264 cases respectively). RESULTS: Abnormal amniotic fluid digestive enzyme profile (vomiting of bile or digestive secretion leakage) was observed in 8/10 MMIHS cases. These profiles were observed in 7/63 controls; 80% sensitivity (95%CI = 55%-100%); 89% specificity (95%CI = 81%-96%). Fetal urinalysis was normal in 12/12 MMIHS cases except high calcium (>0.6 mmol/l). This profile was observed in 33/264 megabladder control cases; 100% sensitivity; 98.7% specificity (95%CI = 83.5%-91.5%). CONCLUSION: For the first time, we propose a prenatal diagnosis of MMIHS based on amniotic fluid digestive enzyme assay and on fetal urinalysis.     

Megacystis-microcolon-intestinal hypoperistalsis syndrome: the difficulties with antenatal diagnosis. Case report and review of the literature

Megacystis on antenatal scan in female fetuses is rare and has serious diagnostic implications. We report two cases of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) in female infants in whom antenatal scan abnormalities were identified, but the diagnosis not made until after delivery. MMIHS is a rare autosomal recessive condition which is usually lethal in the first year of life. Prenatal diagnosis is hampered by the lack of specific diagnostic findings on ultrasound and the absence of an identified genetic locus. The prenatal findings in MMIHS are reviewed and contrasted with those of other causes of lower abdominal masses on antenatal ultrasound.     

Megacystis-microcolon-intestinal hypoperistalsis syndrome in two male siblings

Two male sibs with severe congenital megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) are presented. Both had enlarged bladder and hydronephrosis due to reduced bladder emptying, decreased bowel motility, and malrotation of the colon. Repeated careful ultrasound examination of the urinary tract in the second sib failed to show significant bladder enlargement prior to 25 weeks' gestation, which has been considered to be a reliable prenatal diagnostic sign for MMIHS. Slight bilateral enlargement of the renal pelves was noted at 21 weeks' gestation, and this may represent the earliest prenatally-detectable observation in this disease. Although more females than males with this condition have been reported, our cases provide support for an autosomal recessive mode of inheritance with a similar recurrence risk for both sexes.     

Megacystis-microcolon-intestinal hypoperistalsis syndrome. Antenatal appearance in two cases.

Two cases with severe congenital megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) are presented. This is a rarely encountered syndrome in neonates and 45 cases have earlier been reported. The disease is usually lethal and it now seems clear that MMIHS is an autosomal recessive disorder. The enlarged bladder, typical of this syndrome, is however easy to define by ultrasound, sometimes even in early pregnancy. The concomitant finding of a dilatation of the urinary tract and the absence of oligohydramnios may lead the physician to suspect the diagnosis. Because of the information available from sonography, appropriate investigations can be undertaken immediately after delivery. Prenatal ultrasound examination in subsequent pregnancies is recommended.     

Congenital midline porencephaly. Prenatal sonographic findings and review of the literature

A case of congenital midline porencephaly, including the prenatal sonographic findings, is presented. A review of the literature showed that six cases of congenital midline porencephaly have been reported, though none had sonographic evaluation in the prepartum period. The prenatal sonographic diagnosis of this rare disorder is discussed along with the clinical and pathologic findings and outcome of all reported cases.     

Fetal facial profile in Pallister-Killian syndrome

Pallister-Killian syndrome (PKS) is a sporadic chromosomal anomaly, caused by a tissue-specific mosaic distribution of an additional isochromosome 12p. About 60 cases of prenatal diagnosis of PKS have been reported. Only 1 case of PKS is described on the basis of prenatal screening, presenting increased nuchal translucency. An abnormal fetal facial profile is described prenatally as sonographic evidence of PKS. We report a case of prenatal diagnosis in a fetus undergoing second-level scan due to positive triple screen with ultrasound features of PKS.     

Aicardi syndrome: prenatal sonographic findings. A report of two cases

The prenatal sonographic findings in two children with Aicardi syndrome are reported.     

Prenatal diagnosis of complete trisomy 9: a case report and review of the literature

Complete trisomy 9 is a very rare chromosome aneuploidy, associated with specific patterns of multisystem dysmorphism and a wide spectrum of congenital anomalies. We present a case of complete trisomy 9 with prenatal sonographic findings in the second trimester. The combination of sonography and karyotyping from cordocentesis enabled us to establish the prenatal diagnosis. An additional clinical feature of this syndrome that has not been reported previously is an aortopulmonary communication. A review of the literature specifically dealing with prenatal sonographic findings with complete trisomy 9 is also presented.     

Pallister-Killian syndrome: difficulties of prenatal diagnosis

The first prenatal diagnosis of Pallister-Killian syndrome (PKS) was reported by Gilgenkrantz et al. in1985. Since this report, about 60 prenatal cases have been reported but both sonographic and cytogenetic diagnoses remain difficult. Although ultrasound anomalies such as congenital diaphragmatic hernia, polyhydramnios and rhizomelic micromelia in association with fetal overgrowth are very suggestive of the syndrome, they are inconstant and they may even be absent. The mosaic distribution of the supernumerary isochromosome 12p greatly increases these difficulties. No prenatal cytogenetic technique is sensitive enough to ensure prenatal diagnosis and false-negative results have been described on fetal blood, chorionic villi and amniocentesis. We report here two prenatal cases of PKS which illustrate the great variability of the fetal phenotype. In reviewing the 63 reported cases, we attempt to determine ultrasound indicators of the syndrome and to define a cytogenetic strategy. In cases where ultrasound indicators are present, our proposal is first to perform chorionic villus or placental sampling and then amniocentesis when the first cytogenetic result is normal. Fetal blood sampling is the least indicated method because of the low frequency of the isochromosome in lymphocytes. In this cytogenetic strategy, fluorescent in situ hybridization (FISH) and especially interphase FISH on non-cultured cells increases the probability or identifying the isochromosome. A misdiagnosis remains possible when ultrasound is not contributory; the identification of new discriminating ultrasound indicators would be very helpful in this context.     

Prenatal features of Noonan syndrome.

We report six cases of Noonan syndrome which presented prenatally with sonographic abnormalities. These included increased nuchal fluid, short femora, pleural effusions, hydrops, cardiac and renal abnormalities. A review of all cases of Noonan syndrome seen at two regional genetics centres confirms the association with these sonographic abnormalities. These cases demonstrate the diversity of prenatal presentation of Noonan syndrome and highlight the need to consider this diagnosis, particularly when faced with a fetus with a normal karyotype and varying degrees of oedema or hydrops, with a short femur length.     

Prenatal sonographic findings and hematological abnormalities in fetuses with transient abnormal myelopoiesis with Down syndrome

OBJECTIVES: To determine relevant prenatal findings of transient abnormal myelopoiesis (TAM) that have important prognostic implications. METHODS: The prenatal and postnatal medical records of all cases with confirmed TAM associated with Down syndrome were reviewed retrospectively, with emphasis on prenatal sonographic findings, fetal blood analysis, neonatal outcomes, and causes of death. RESULTS: From January 1992 to December 2005, seven cases were confirmed postnatally as having TAM associated with Down syndrome. Sonography demonstrated hydrops with hepatomegaly in four, and isolated hepatomegaly in two of these seven cases. There were no findings suggestive of cardiac failure in cases of hydrops. Fetal blood analysis revealed elevated liver enzyme levels in six cases and hypoalbuminemia in four cases. Comparison of sonographic findings with fetal blood findings demonstrated an association between hydrops and hypoalbuminemia. Four of the seven cases were fatal. All fatal cases were associated with hydrops and the main cause of death was coagulopathy due to liver failure, which may have resulted from infiltration of the liver by blast cells. CONCLUSIONS: Fetal TAM is associated with hepatomegaly and elevated liver enzyme levels. The prenatal finding with prognostic implications is hydrops, which may result from hypoalbuminemia due to liver failure.     

Megacystis-microcolon-intestinal hypoperistalsis syndrome: a case report.

Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a rare congenital disorder characterized by a dilated, non-obstructive urinary bladder and hypoperistalsis of the gastrointestinal tract, which is considered lethal. About 90 patients have been reported, predominantly female. We present the case of a female newborn with MMIHS in whom antenatal ultrasound was suggestive for the diagnosis, which was confirmed after delivery. Diagnostic features by antenatal ultrasound are described.     

Split notochord syndrome - prenatal ultrasonographic diagnosis.

Split notochord syndrome is a rare condition that is characterized by a persistent connection of the gut and dorsal skin of the back, an enteric cyst and vertebral anomalies. We present two cases in which prenatal ultrasound showed polyhydramnios. In one case it was associated with vertebral abnormalities and a right-sided mediastinal cyst found to be the stomach. Postnatal evaluation confirmed the diagnosis of split notochord syndrome. The association of sonographic findings of hydramnios, thoracic cysts and vertebral anomalies suggests prenatal diagnosis of split notochord syndrome.     

Progressive development of sonographic features in prenatal diagnosis of Apert syndrome--case report and literature review

Apert syndrome is characterized by craniosynostosis, midfacial malformations and symmetrical syndactyly of the hands and feet. We report a case of prenatal sonographic diagnosis of Apert syndrome. Mild ventriculomegaly with normal head shape observed at 22 weeks gestation, followed by colpocephaly at 25 weeks gestation and bilateral syndactyly and subsequent craniosynostosis at 28 weeks, led to the prenatal diagnosis of Apert syndrome. The diagnosis was confirmed by physical examination and molecular study after birth. Additionally the authors present the review of literature on prenatal sonographic diagnosis of Apert syndrome.     

Prenatal sonographic diagnosis of Klippel-Trenaunay-Weber syndrome associated with umbilical cord hemangioma

Klippel-Trenaunay-Weber syndrome (KTW), also known as angio-osteohypertrophy syndrome, is a complex developmental disorder characterized by asymmetric hemi-hypertrophy of limbs and trunk due to bony and soft tissue overgrowth that may extend across the midline, varicose veins, and cutaneous hemangiomata. This rare syndrome has been previously described in the prenatal period by ultrasonography, and in literature, there are quite different presentation of cases. We describe a case suggested as a KTW syndrome by prenatal ultrasonography. The sonographic appearance of an unilateral leg hypertrophy associated with irregular echolucent cystic areas was consistent with KTW syndrome. A spheric, weak-echogenic mass without any active blood flow located in the umbilical cord revealed by color Doppler ultrasonography was an unexpected finding. The postpartum examination confirmed the prenatal diagnosis.     

Prenatal sonographic patterns in six cases of Wolf-Hirschhorn (4p-) syndrome

This multicentric study presents 6 cases of Wolf-Hirschhorn syndrome (deletion of 4p) detected after a sonographic prenatal diagnosis of early intrauterine growth retardation with fetal abnormalities. Standard karyotyping on regular G-banding during pregnancy was normal in half of the cases. Fortunately, the associated sonographic signs of a typical face, cystic cerebral lesions, midline fusion defects and bilateral renal hypoplasia may help to refine specific indications for high-resolution banding and molecular analysis by in situ hybridization.     

Prenatal sonographic features of congenital lobar emphysema

The prenatal sonographic features of congenital lobar emphysema (CLE) have not been well characterised. Five cases have been reported in the literature and on all these occasions either an echogenic (3) or a cystic (2) lung lesion was detected prenatally and the diagnosis was confirmed after the operation. This is the sixth case of CLE in the literature with prenatal sonographic features documented. The prenatal scans of a 23-year-old lady performed at 22 weeks of gestation revealed cystic lesions and increased echogenicity of the right fetal lung. There were no other anomalies and the karyotype was normal. The lesion decreased in size at 28 weeks and the baby was born by a normal vaginal delivery at 41 weeks. CT scan performed on day 6 confirmed cystic changes on the right lung with compression of the right lower lobe. A repeat CT scan performed at 4 months revealed extensive cystic changes in a hyper-inflated right lung and mediastinal shift to the left. At operation, abnormally inflated right upper and middle lobes were found suggesting a CLE. There were no subsequent complications after removal and histology confirmed CLE. The reported cases are reviewed and the prenatal sonographic features of CLE are discussed.     

Prenatal diagnosis of a fetus with distal 10q trisomy.

Distal 10q trisomy is a well-defined but rare syndrome. Most cases are diagnosed in infancy or in childhood and rarely include prenatal findings. We present a case of fetal distal 10q trisomy with abnormal prenatal sonographic findings. A 19-year-old primigravida was referred for genetic counselling at 18 gestational weeks because her husband had a familial history of congenital anomalies. Genetic amniocentesis was thus performed and showed fetal distal 10q trisomy (10q24.1-->qter), 46,XX,der(22)t(10;22)(q24.1;p11.2)pat, resulting from paternal t(10;22) reciprocal translocation. Level II ultrasonograms further demonstrated bilateral hydronephrosis, ventricular septal defect and facial dysmorphism ascertained by three-dimensional ultrasound. The pregnancy was terminated at 22 gestational weeks. Post-mortem autopsy confirmed the sonographic findings. We suggest that abnormal prenatal sonographic findings such as cardio-vascular, renal and facial malformations should alert cytogeneticists to search for subtle chromosomal abnormalities.     

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.     

Prenatal ultrasound diagnosis of a case of Pfeiffer syndrome without cloverleaf skull and review of the literature

Pfeiffer syndrome is characterized by bilateral coronal craniosynostosis, midface hypoplasia, beaked nasal tip, broad and medially deviated thumbs and great toes. Originally, it was described in eight persons from three generations in a pedigree consistent with an autosomal dominant transmission. Since then, several reports have documented its high clinical and genetic heterogeneity. The condition is usually detected in the newborn period or later, and very few prenatal ultrasound diagnoses have been reported. We present a case of Pfeiffer syndrome prenatally diagnosed at 20 weeks' gestation, in which the sonographic features of craniosynostosis, hypertelorism associated with an extreme proptosis, and broad thumb led to the diagnosis, confirmed after termination of pregnancy by dysmorphological, pathological and radiological evaluation. DNA analysis of the fibroblast growth factor receptor 2 (FGFR2) showed a missense mutation consisting in a transversion G --> C at nucleotide 870. This led to a Trp290Cys amino acidic substitution.We discuss the relevant findings of our and previously published cases. Our report demonstrates that a careful sonographic examination can lead to an early prenatal diagnosis of Pfeiffer syndrome also in cases without cloverleaf skull.