Ivemark syndrome with agenesis of the corpus callosum: a case report with a review of the literature

Asplenia associated with situs ambiguus, symmetric liver, bilateral trilobulated lungs, and a complex heart defect was diagnosed on autopsy in a 14-day-old infant. Furthermore, examination of the brain displayed agenesis of the corpus callosum (ACC) with pachygyria and hydrocephalus. The characteristic association of asplenia with visceroatrial heterotaxia is traditionally named after the Swedish pediatrician, Ivemark. Although exceptional, association of Ivemark syndrome with callosal agenesis has been reported recently. The concept of ‘developmental fields’ describes morphogenetically reactive units of the embryo determining and controlling the development of complex structures in a hierarchical manner. Lateralization defects such as situs inversus, asplenia or polysplenia due to defective left–right axis development, as well as decussation defects such as ACC, are considered as defects of the primary developmental field. Therefore, additional callosal agenesis in Ivemark syndrome may be a coherent and synchronic defect in the primary developmental field rather than a causally independent malformation. Copyright © 2002 John Wiley & Sons, Ltd.     

Disorders of prosencephalic development

Abnormal ventral induction may result in disorders of formation, cleavage, and midline development of prosencephalic structures. Holoprosencephaly is a developmental field defect of impaired cleavage of prosencephalon. The most widely accepted classification of holoprosencephaly recognizes three major varieties: the alobar, semilobar and lobar types, according to the severity of the malformation. The brain malformations, characterized by the fusion of the cerebral hemisphere along the midline are commonly associated with facial anomalies. Corpus callosum agenesis and septo-optic dysplasia are disorders of prosencephalic midline development, and usually have less severe presentations but still, affected subjects may suffer from neurodevelopmental retardation, and/or endocrinologic and visual disorders. In this article we report an up-to-date of pathogenesis, prenatal sonographic findings, differential diagnosis and prognosis of the aforementioned anomalies. Copyright © 2009 John Wiley & Sons, Ltd.     

Dandy – Walker syndrome and corpus callosum agenesis in 5p deletion

5p deletion syndrome commonly known as cri du chat is well described in affected neonates with catlike cry and hypotonia. Karyotyping will usually show a deletion of the short arm of one chromosome 5 with variable breakpoints. Only a few cases have been reported prenatally, and the fetal form of the syndrome has not been clearly individualised. We report a new case of 5p deletion syndrome diagnosed prenatally in association with Dandy–Walker syndrome and agenesis of the corpus callosum. Other brain anomalies have been reported previously, but this unusual association suggests the use of a specific probe in the investigation of these malformations. Copyright © 2005 John Wiley & Sons, Ltd.     

Congenital cervical teratoma,associated with agenesis of corpus callosum and a subarachnoid cyst

Cervical teratoma is a neoplasm composed of embryonic tissues with representation of all three germ layers. We report an extremely rare case of fetal cervical teratoma presenting at 24 weeks of gestation. A submaxillary mass and agenesis of corpus callosum were identified on ultrasonography, associated with agenesis of corpus callosum and a subarachnoid cyst. Copyright © 2005 John Wiley & Sons, Ltd.     

Prenatal diagnosis of renal agenesis in a twin gestation

Bilateral renal agenesis is a lethal congenital anomaly. It appears to be transmitted in a polygenic pattern. The prenatal ultrasound findings consist of severe oligohydramnios, absence of the fetal bladder, and failure to identify fetal kidneys. Twin gestations with renal agenesis have been described in the paediatric literature. We detail a case of a patient with two prior affected pregnancies with bilateral renal agenesis. Her latest pregnancy was diagnosed prenatally, with one fetus with bilateral and the other fetus with unilateral renal agenesis. The ultrasound findings should be differentiated from the stuck twin phenomenon.     

Lobar holoprosencephaly: prenatal MR diagnosis with postnatal MR correlation

Holoprosencephaly is a congenital anomaly characterized by lack of cleavage of the prosencephalon. Although, relatively rare, it is the most common anomaly that involves both the brain and the face. Prenatal diagnosis of this anomaly using ultrasonography, particularly of the less severe forms, is difficult. Magnetic resonance imaging has recently become an important complement to US in prenatal diagnosis of CNS anomalies. We herein report a patient in whom, at 23 weeks of gestation, US suggested agenesis of the corpus callosum and in whom, at 24 weeks of gestation, MRI correctly diagnosed lobar holoprosencephaly, which was confirmed by a postnatal MRI at 3 weeks of age. Copyright © 2005 John Wiley & Sons, Ltd.     

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. Copyright © 2001 John Wiley & Sons, Ltd.     

Prenatal ultrasound diagnosis of Toriello–Carey syndrome

Toriello–Carey syndrome is a rare malformative complex, described for the first time in 1988, characterized by agenesis of the corpus callosum, facial anomalies, cardiac defects and hypotonia. Relatively few neonatal cases have been reported. We describe here the first prenatal ultrasound diagnosis of the syndrome based on the detection of agenesis of the corpus callosum and spongious cardiomyopathy in a 22-week-old fetus of a couple with positive family history. The first sib of the couple was diagnosed with Toriello–Carey syndrome at 1 year of age, and had, in addition to the typical facial anomalies not detectable by ultrasound, agenesis of the corpus callosum and the same heart lesion (spongious cardiomyopathy). This report demonstrates that prenatal diagnosis of Toriello–Carey syndrome is feasible in the second trimester of pregnancy. Copyright © 2002 John Wiley & Sons, Ltd.     

Fetal renal artery flow velocity waveforms in the presence of congenital renal tract anomalies

Colour Doppler flow mapping of the renal arteries and subsequent pulsed Doppler measurement of impedance to flow in these vessels were attempted in 33 fetuses with postnatally confirmed renal pathology. The majority presented with unilateral or bilateral hydronephro-sis (n = 21) and bilateral renal agenesis (n = 8). Renal artery blood flow could be visualized in all, except for the eight cases of bilateral renal agenesis. Bilateral flow velocity recordings were collected in six out of 12 cases of bilateral hydronephrosis and in five out of nine cases of unilateral hydronephrosis. The pulsatility index (PI), as a measure of downstream impedance, was in the normal range in 16 out of 18 kidneys (88 per cent) in bilateral hydronephrosis and in 12 out of 14 kidneys (85 per cent) in unilateral hydronephrosis. The PI was significantly higher in severe hydronephrosis compared with mild hydronephrosis. In four cases of unilateral multicystic kidney, the PI was always higher on the affected side. Colour Doppler flow mapping and pulsed Doppler evaluation may be helpful in our understanding of renal vascularization in renal pathology and in confirming the diagnosis of renal agenesis.     

The early prenatal sonographic diagnosis of renal agenesis: Techniques and possible pitfalls

Out of 13 252 cases in which fetal bilateral echogenic kidneys were detected by transvaginal sonography between 12 and 18 weeks' gestation, there were nine fetuses where oval hypoechogenic masses were detected in the renal bed. In five fetuses where hypoechogenic masses in the renal bed were sonographically visualized, postabortal examination was compatible with renal agenesis and the hypoechogenic masses proved to be enlarged adrenals. In three additional cases, unilateral renal agenesis was accompanied by unilateral enlarged adrenals, radiologically confirmed postnatally. In one case, a false-positive sonographic diagnosis of Potter syndrome was made because of bilateral hypoechogenic masses in the renal bed. Postabortal examination detected hypoplastic kidneys, but of normal histology, in a dyskaryotic fetus with trisomy 22. In four cases of renal agenesis, the amniotic fluid was of normal volume until the 17th week. In two of the five cases of Potter syndrome, a cystic structure, compatible with the urinary bladder, was detected in the pelvis at 14 weeks. The diagnostic criteria for renal agenesis in the early fetus differ from those used in the second half of gestation.     

Magnetic resonance imaging of the fetus: A study of 20 cases performed without curarization

Twenty patients underwent magnetic resonance imaging (MRI) at a mean gestational age of 32 weeks. There were 12 patients with suspected fetal brain abnormality and four with intrauterine growth retardation (IUGR), while the remaining four cases were studied for other reasons. The MRI examinations were performed on a 0.5 Tesla machine, with surface coils. One minute acquisition time T1 sequences were used. All the studies were performed without fetal curarization, and only under maternal sedation using flunitrazepam given per os 1 h before MRI examination. Three examinations were incomplete because of fetal movement artefacts. In the remaining cases, MRI allowed the examination of fetal brain anatomy. In five cases, it helped to differentiate isolated hydrocephalus and corpus callosum agenesis. Sub-ependymal nodules were depicted in a case of fetal tuberous sclerosis. One suspected arachnoid cyst was proved to be an ultrasound artefact. Decreased fetal fat on MR images was correlated with low birth weight in cases of IUGR. Due to its better spatial resolution, ultrasonography was more accurate for the diagnosis of facial and lumbar anomalies. Fetal MRI may be performed without curarization. Surface coils allow the detailed analysis of brain parenchyma, and thus MRI is especially useful in the difficult prenatal diagnosis of fetal brain abnormalities.     

Assessment and management of fetal agenesis of the corpus callosum

Prenatal counselling for fetal agenesis of the corpus callosum is difficult as the prognosis until now has been so uncertain. We have reviewed the current world English literature to provide the best probabilistic information for prospective parents. In total, there are 70 cases where the diagnosis was made prenatally. The diagnosis of apparently isolated agenesis of the corpus callosum (in the absence of other sonographically detectable anomalies) appears to carry an excellent prognosis, with an 85 per cent chance of a normal developmental outcome and a 15 per cent risk of handicap. Fetal karyotyping is recommended as there is a 1 in 10 risk of aneuploidy. If other anomalies are detected prenatally, the outcome is very poor. Termination of pregnancy is advised in these circumstances.     

Pancreatic and sacral agenesis in association with maternal diabetes mellitus: Case report

Sacral agenesis was diagnosed sonographically in the fetus of a diabetic mother and pancreatic agenesis was found additionally at autopsy.     

The BOR syndrome and renal agenesis-prenatal diagnosis andfurther 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.     

Apert syndrome: what prenatal radiographic findings should prompt its consideration?

Apert syndrome was diagnosed in a newborn with typical facial and digital features whose only detected prenatal abnormality had been agenesis of the corpus callosum. This prompted a review of the central nervous system findings in all cases of Apert syndrome treated at the Craniofacial Center Boston Children's Hospital between 1978 and 2004. Two of 30 patients with Apert syndrome had prenatal identification of mild dilatation of the lateral cerebral ventricles and complete agenesis of the corpus callosum (ACC) documented with both ultrasound and MRI. Both had the common S252W mutation of FGFR2. Though cranial and orbital malformations typical of Apert were eventually seen in these fetuses in the third-trimester, even in retrospect, these were not detectable at mid second-trimester, ultrasound screening for congenital malformations. Hand malformations also went undetected in the second-trimester despite extensive imaging by experienced radiologists. We conclude that prenatal ultrasonographic identification of mild ventriculomegaly or ACC should stimulate a careful search for features of Apert syndrome and prompt follow-up imaging to look for bony abnormalities that have later onset. Prenatal molecular testing for Apert mutations should be considered in cases of mild ventriculomegaly and ACC. Copyright © 2006 John Wiley & Sons, Ltd.     

Prenatal diagnosis of gall bladder anomalies—report of 17 cases

We describe here 17 cases of fetal gall bladder anomalies, detected as early as the 14th week of gestation, out of 10 016 fetal systemic examinations performed by us in the last 6 years (015 per cent). In seven cases, agenesis of the fetal gall bladder was detected. The diagnosis was confirmed by post-abortal examination in five cases and in two post-partum. In six other cases, a left-sided gall bladder and in one case, a ‘floating’ gall bladder were detected at 15 weeks' gestation. In two cases, a septated or bilobed gall bladder was visualized. None of these 15 cases was dyskaryotic, but in five cases, two with agenesis and three left-sided gall bladders were associated with other fetal malformations. In two other cases, the gall bladder appeared dysmorphic on sonographic examination and in both of them intrauterine growth retardation and other anomalies were detected. Trisomy 18 was diagnosed by amniocentesis in one of them. According to our experience, failure to visualize the fetal gall bladder by the 15th gestational week is diagnostic of its absence and should raise the differential diagnosis between gall bladder atresia, which has a good prognosis, and external biliary atresia, which has a poor prognosis. Further experience is needed to characterize the various gall bladder malformations and their prognosis.     

The prenatal diagnosis of joubert's syndrome of familial agenesis of the cerebellar vermis

The prenatal diagnosis by ultrasound examination of Joubert's syndrome of familial agenesis of the cerebellar vermis is described allowing termination of pregnancy ai 26 weeks gestation. The diagnosis was made by a comparison of the prenatal ultrasound examination with computerized axial tomography obtained from the siblings with the same condition.     

Prenatal diagnosis of Juberg–Hayward syndrome

Juberg–Hayward syndrome is a rare autosomal recessive syndrome characterised by the association of growth retardation, microcephaly, cleft lip and palate, and thumb and radial ray abnormalities. To date, no prenatal cases have been reported. Here, we report on the first prenatal case of Juberg–Hayward syndrome. The diagnosis was established following fetopathological study. Besides the cardinal features of the syndrome, this prenatal case was remarkable for the severity of the short arm malformation and by the finding of big toe agenesis and cerebral abnormalities including hydrocephalus, agenesis of corpus callosum, and cerebellar hypoplasia. We conclude that the diagnosis of Juberg–Hayward syndrome can be discussed prenatally following ultrasound diagnosis of the association of intrauterine growth restriction, microcephaly, thumb/radial anomalies, and cleft lip/palate. Copyright © 2005 John Wiley & Sons, Ltd.     

Prenatal diagnosis of partial agenesis of the corpus callosum in a fetus with thanatophoric dysplasia type 2

A fetus with thanatophoric dysplasia type 2 (TD2) associated with cloverleaf skull and abnormal development of the corpus callosum is reported. This case represents the first prenatal direct visualization of a partial agenesis of the corpus callosum (ACC) using high-resolution ultrasonography and colour power Doppler, which was confirmed by post-mortem magnetic resonance imaging (MRI). The causal link between cloverleaf skull in TD and partial ACC is discussed. Copyright © 2002 John Wiley & Sons, Ltd.     

Prenatal diagnosis of sacrococcygeal teratoma with constitutional partial monosomy 7q/trisomy 2p

We report the prenatal diagnosis of a fetus with sacrococcygeal teratoma and facial dysmorphism attributed to a constitutional terminal deletion of chromosome 7q and partial trisomy of chromosome 2p likely resulting from a de novo balanced translocation. The cytogenetic abnormality was diagnosed prenatally after sonographic detection of teratoma and confirmed on peripheral blood cells at birth. The newborn died of post-operative complications at seven days of age. FISH analysis demonstrated haploinsufficiency of HLXB9, a gene identified in the triad of a presacral mass (teratoma or anterior meningocele), sacral agenesis, and anorectal malformation, which constitutes the Currarino syndrome. Despite the absence of other features of the triad, the teratoma observed in the fetus we describe might represent a partial form of Currarino syndrome. Copyright © 2003 John Wiley & Sons, Ltd.