Application of the three-dimensional maximum mode in prenatal diagnosis of Apert syndrome

Apert syndrome is a rare disorder characterized by coronal craniosynostosis, syndactyly, brachycephaly, midfacial hypoplasia, and central nervous system anomalies, among other malformations. We present a case of Apert syndrome examined at 22 + 0 weeks' gestation. Three-dimensional maximum mode was decisive for the correct prenatal diagnosis by demonstrating the cranial deformities.     

Prenatal diagnosis of Apert syndrome: report of two cases

Two de novo cases with Apert Syndrome detected prenatally are presented herein. In the first, fetal ultrasound findings of syndactyly of the hands, craniosynostosis and proptosis resulted in a prenatal diagnosis in the nineteenth week of gestation. This is the earliest prenatal diagnosis of this syndrome in a not-at-risk case. Following counseling, this pregnancy was terminated and subsequent pathological examination and DNA analysis confirmed the diagnosis of Apert Syndrome and coarctation of the aorta. In the second case, fetal ultrasound at 21 weeks' gestation revealed a hypoplastic left heart and clover-leaf skull. Following counseling, this pregnancy was also terminated. Further examination of the fetus and DNA analysis led to a diagnosis of Apert Syndrome. These cases emphasize the need to complete a thorough fetal ultrasound in cases with potentially lethal cardiac abnormality and the importance of incorporating a fetal pathologist, as well as a medical geneticist, in the investigations performed after delivery or pregnancy termination when a fetal abnormality is detected on ultrasound.     

Prenatal diagnosis of Apert syndrome with widely separated cranial sutures

A 35-year-old Taiwanese woman visited us for prenatal evaluation in the 20th week of pregnancy. Both clinical observation of the mother and analysis of maternal DNA indicated a diagnosis of Apert syndrome. Sonographic examination of the fetus demonstrated findings that were consistent with this diagnosis; however, no prematurely fused cranial sutures were observed. The pregnancy was terminated after genetic counselling and fetal DNA analysis showed the same mutation as found in the mother. Autopsy of the abortus revealed the same findings as were detected by sonography; however, all cranial sutures were widely separated. These findings indicate that, in Apert syndrome, craniosynostosis and syndactyly may develop asynchronously up to 20 weeks of pregnancy.     

Rapid detection of de novo P253R mutation in FGFR2 using uncultured amniocytes in a pregnancy affected by polyhydramnios,Blake's pouch cyst,and Apert syndrome

ObjectiveTo present prenatal ultrasound and molecular genetic diagnosis of Apert syndrome.Case ReportA 30-year-old, gravida 3, para 2 woman was referred for genetic counseling at 32 weeks of gestation because of polyhydramnios and craniofacial and digital abnormalities in the fetus. She had undergone amniocentesis at 18 weeks of gestation because of maternal anxiety. Results of amniocentesis revealed a karyotype of 46,XX. A prenatal ultrasound at 32 weeks of gestation revealed a female fetus with a fetal biometry equivalent to 32 weeks, polyhydramnios with an increased amniotic fluid index of 26.1 cm, frontal bossing, midface hypoplasia, hypertelorism, Blake's pouch cyst with an apparent posterior fossa cyst in communication with the fourth ventricle on axial images, digital fusion, and bilateral syndactyly of the hands and feet. A DNA testing for the FGFR2 gene was immediately performed using uncultured amniocytes obtained by repeated amniocentesis, which revealed a heterozygous c.758C>G, CCT>CGT transversion leading to a p.Pro253Arg (P253R) mutation in the FGFR2 gene. Subsequently, a diagnosis of Apert syndrome was made. Molecular analysis of the FGFR2 gene in the parents did not reveal such a mutation. The fetus postnatally manifested frontal bossing, midface hypoplasia, and bilateral syndactyly of the hands (mitten hands) and feet.ConclusionPrenatal diagnosis of polyhydramnios, frontal bossing, and midface hypoplasia associated with brain and digital abnormalities should include a differential diagnosis of Apert syndrome. A molecular analysis of FGFR2 using uncultured amniocytes is useful for rapid confirmation of Apert syndrome at prenatal diagnosis.     

Prenatal diagnosis of sporadic Apert syndrome: a sequential diagnostic approach combining three-dimensional computed tomography and molecular biology

Apert syndrome is characterized by coronal craniosynostosis, midfacial hypoplasia, symmetrical syndactyly of the hands and feet described as 'mitten-like' with varying degrees of mental retardation. It results from a mutation of the fibroblast growth factor-2 (FGFR2) gene. In the absence of a family history, prenatal diagnosis may be difficult based on sonography alone. We report a case in which the prenatal diagnosis of Apert syndrome was suspected by ultrasonography, established by three-dimensional computed tomography scan (3DTS) and confirmed by the detection of a mutation on amniotic cells. This underscores the usefulness of a sequential diagnostic approach combining 3DTS and molecular biology in cases in which sonography alone is not con- clusive.     

Contribution of tridimensional sonography and magnetic resonance imaging to prenatal diagnosis of Apert syndrome at mid-trimester

A diagnosis of Apert syndrome, suspected at 24 weeks' gestation after conventional sonography showing turribrachycephaly and syndactyly of hands and feet, was confirmed at 26 weeks' gestation by tridimensional sonography and magnetic resonance imaging. This is only the second prenatal diagnosis reported at mid-trimester, excluding cases published from affected mothers or in connection with a context of recurrence. Additional findings have been collected from tridimensional sonography (mid-facial hypoplasia, downslanting palpebral fissures) and from magnetic resonance imaging (verticalization of the clivus and flattened angle of the cranial base).     

Prenatal diagnosis of Apert syndrome

OBJECTIVE: The role of the human fibroblast growth factor receptor (FGFR) gene family in current prenatal diagnosis and management of craniosynostosis syndromes and skeletal dysplasias is discussed. METHOD: We present the antenatal ultrasound findings, diagnosis, and management of 2 cases of Apert syndrome before and after molecular prenatal diagnosis was available. RESULTS AND CONCLUSION: Discovery of mutations in FGFR genes now allows the definitive antenatal diagnosis of Apert syndrome, other craniosynostosis syndromes, and skeletal dysplasias.     

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.     

Prenatal diagnosis of Pfeiffer syndrome type II

Pfeiffer syndrome is an autosomal dominant disorder characterized by coronal craniosynostosis, midface hypoplasia, broad thumbs and great toes. On the basis of clinical findings, three subtypes have been delineated. The clinical variability of Pfeiffer syndrome as well as other causes of craniosynostosis can make a prenatal diagnosis based on sonography alone difficult. We describe a fetus in whom sonographic findings (including 3D ultrasound) suggested a Pfeiffer syndrome type II and in which subsequent molecular analysis verified the diagnosis by identifying a de novo mutation in the FGFR2 gene. To the best of our knowledge, this is the first report of a prenatal molecular diagnosis of Pfeiffer syndrome in a patient without family history.     

Prenatal diagnosis of Meckel syndrome: a case report.

OBJECTIVE: To demonstrate the major sonographic findings associated with Meckel syndrome and to emphasize the importance of prenatal sonography in helping to establish the correct diagnosis. SUBJECTS: Two fetuses with prenatal diagnosis of Meckel syndrome were sonographically evaluated. RESULTS: Both fetuses were demonstrated to have evidence of renal cystic dysplasia, occipital cephalocele and postaxial polydactyly. One case was diagnosed at 16 weeks of gestation whereas the other was detected at 36 weeks. Of interest, the first case had only unilateral renal cystic dysplasia and contralateral renal agenesis and mild degree of oligohydramnios. The other related anomalies which were not detected prenatally included cerebellar hypoplasia in case 1 and micrognathia in case 2. CONCLUSION: The main sonographic findings included renal cystic dysplasia, occipital cephalocele and postaxial polydactyly.     

Sonographic features of lethal multiple pterygium syndrome at 14 weeks

Lethal multiple pterygium syndrome is a rare inherited disorder. Previous reports suggest that the diagnosis may be based on prenatal sonographic demonstration of severe limb flexion, absence of fetal motion, and a large cystic hygroma in the second and third trimesters. We present the sonographic features and postmortem features of a fetus with lethal multiple pterygium syndrome at 13 weeks of gestation, which shows that the condition can possibly be diagnosed in the first trimester of pregnancy.     

First-trimester diagnosis of hydrolethalus syndrome in a Chinese family

We report a case resembling hydrolethalus syndrome in a Chinese family. Fetal polydactyly, syndactyly, encephalocele and cardiac malformation were detected on ultrasound examination at 12 weeks' gestation. Termination of pregnancy was performed, and postmortem examination confirmed the findings. This is the first report of a first-trimester prenatal diagnosis of hydrolethalus syndrome in the Chinese population.     

Prenatal diagnosis of Seckel syndrome at 21 weeks’ gestation and review of the literature

Background: The Seckel syndrome is an autosomal recessive inherited disorder that characterized severe pre- and post-natal growth restriction, microcephaly and a bird-like fetal head appearance. A few clinical reports revealed prenatal sonographic findings in the literature.

Case: A 29-year-old, Turkish, gravid 3, para 2, woman was referred to our center for further evaluation of a suspicion of microcephaly at 21 weeks’ gestation. The couple was third degree consanguineous. Detailed 2- and 3-dimensional sonography scan revealed a bird-headed appearance, prominent eyes with hypotelorism, a severe microcephaly (bi-parietal diameter and head circumference were both ?95th percentile), low-set and prominent ears. All sonographic findings suggested Seckel syndrome and the couple elected termination of pregnancy in the present case.

Summary: Seckel syndrome should be kept in mind in the differential diagnosis of severe microcephaly, accompanied by fetal growth restriction. 3D ultrasound is a useful adjuvant to routine 2D sonography for prenatal diagnosis of the syndrome and can delineate abnormal fetal head appearance (a bird-headed profile).     

Prenatal sonographic appearance of Beare-Stevenson cutis gyrata syndrome: two- and three-dimensional ultrasonographic findings

Beare-Stevenson cutis gyrata syndrome is characterized by craniofacial anomalies, particularly craniosynostosis, ear defects, cutis gyrata, acanthosis nigricans, anogenit anomalies, skin tags, and prominent umbilical stump. The prenatal two- and three-dimensional ultrasonographic findings of this rare condition is reported. The detection was made at 32 weeks of gestation in a woman with polyhydramnios and fetal head anomaly. The ultrasound appearance and postnatal follow-up are presented.     

Brachmann-de Lange syndrome: a cause of early symmetric fetal growth delay

Brachmann-de Lange syndrome is characterized by pre- and postnatal growth retardation, microbrachycephaly, hirsutism, various visceral and limb anomalies and a typical face. A sonographic prenatal diagnosis at mid-trimester is reported in a case of severe, symmetrical fetal growth delay at 20 weeks gestation, with a thickened skin on the forehead, a small nose and a marked depressed nasal bridge, a long philtrum, micrognathia and a persistently flexed right forearm, with a single bone associated to oligodactyly. Due to the severe mental impairment with a commonly estimated intelligence quotient under 60, the pregnancy was terminated after parental consent.     

Late-onset fetal bilateral pleural effusions associated with Down syndrome

Objective

We present two cases of late-onset bilateral fetal pleural effusions associated with fetal Down syndrome.

Prenatal ultrasound diagnosis of Apert's syndrome.

A mother affected with Apert's syndrome was diagnosed by ultrasound scan at 16-17 weeks to have a fetus similarly affected. The typical features of acrocephaly and symmetrical syndactyly were seen. This is probably the first time that this condition has been diagnosed at such a gestation by ultrasound scan. The patient decided to continue the pregnancy, and intrauterine death occurred at 34 weeks. The diagnosis was confirmed by pathological examination.     

Prenatal diagnosis of a 'minor' form of Brachmann-de Lange syndrome by three-dimensional sonography and three-dimensional computed tomography

Brachmann-de Lange syndrome is a congenital disease characterized by severe mental retardation, pre- and postnatal symmetric growth delay, limb defects, visceral anomalies, hirsutism, and a typical face. The authors describe the prenatal sonographic pattern of Brachmann-de Lange syndrome suspected at 20 weeks of gestation, with severe intrauterine growth retardation, facial dysmorphism, cardiac abnormality, and micromelia without the typical defects of the upper limbs. Fetal karyotyping was normal. The diagnosis of a 'minor' form of Brachmann-de Lange syndrome was confirmed at 28 weeks of gestation by using three-dimensional sonography in order to assess precisely the facial dysmorphism and by performing a three-dimensional computed tomography of the upper limbs in order to identify the subtle abnormalities of the radial head and of the first metacarpal bone.     

Typical isolated ectrodactyly of hands and feet: Early antenatal diagnosis

Ectrodactyly is a rare dominant autosomal malformation with variable expression. Herein we report a case early diagnosed by ultrasound at 15 weeks of gestation of isolated ectrodactyly involving the four limbs. The sonographic findings were bilateral split hands and split foot. Diagnosis of typical isolated ectrodactyly was pathologically confirmed. Clinical forms, pathogenesis, differential diagnosis, and early prenatal diagnosis are discussed.     

Typical isolated ectrodactyly of hands and feet: early antenatal diagnosis.

Ectrodactyly is a rare dominant autosomal malformation with variable expression. Herein we report a case early diagnosed by ultrasound at 15 weeks of gestation of isolated ectrodactyly involving the four limbs. The sonographic findings were bilateral split hands and split foot. Diagnosis of typical isolated ectrodactyly was pathologically confirmed. Clinical forms, pathogenesis, differential diagnosis, and early prenatal diagnosis are discussed.