Meckel–Gruber Syndrome: a population-based study on prevalence, prenatal diagnosis, clinical features, and survival in Europe (original) (raw)
Related papers
Meckel Gruber Syndrome diagnosed in two consecutive pregnancies
Proceedings in Obstetrics and Gynecology, 2015
Meckel Gruber syndrome is a lethal, autosomal recessive, multisystemic disorder that is associated with a mutation affecting ciliogenesis. In this report, we present two consecutive pregnancies of a woman complicated with MKS. In the first pregnancy with MKS, the amniotic fluid index was under 1 cm with bilateral polycystic fetal kidneys. Postabortion macroscopic examination of the first fetus revealed multiple congenital anomalies including occipital encephalocele, axial polydactyly and pes equinovarus. Ultrasound examination during the second gestation revealed a singleton pregnancy complicated by MKS. There were multiple congenital anomalies including an occipital encephalocele, polycystic and horseshoe shaped kidneys, axial polydactyly, cleft lip and palate.
First trimester diagnosis of Meckel Gruber syndrome in pregnancy
PubMed, 2004
Meckel Gruber syndrome was originally described by Meckel in 1822, later by Gruber and more recently by Opitz and Howe. 1 It is a lethal autosomal recessive disorder characterized by the triad of encephalocele, polycystic kidneys and polydactyly. Prenatal ultrasonographic diagnosis of this condition has been reported extensively during the second and third trimeter. In the low risk population the estimated prevalence of the condition is about 1 in 20,000 pregnancies. 2 The disorder is more frequently encountered in the children of consanguineously married couples. The prevalence of this disorder in Pakistan is expected to be higher as the recent Pakistan Demographic and Health. Survey (DHS) shows that almost two-thirds of marriages in Pakistan are consanguineous. 3 A case of Meckel Gruber Syndrome diagnosed by ultrasound examination is presented.
P19.06: Meckel Gruber syndrome: prenatal diagnosis and autopsy findings
Ultrasound in Obstetrics & Gynecology, 2012
OBJECTIVE: To analyze prenatal sonographic anomalies detected in fetuses with Meckel Gruber syndrome (MGS), and to correlate these anomalies with autopsy findings. STUDY DESIGN: In a 4-year long prospective study, ultrasound findings were compared with fetal autopsy findings in eight fetuses with MGS out of 107 second-trimester termination of pregnancy (TOP) cases due to fetal malformation diagnosed by second trimester-ultrasound examination at a tertiary referral center. RESULTS: Eight prenatally diagnosed fetuses with MGS were analyzed. Seven cases had classical clinic triad. One case had only polycystic kidneys and polydactyly. Fetal autopsy confirmed all prenatally diagnosed findings associated with MGS; fetal examination added polydactyly in two prenatally undiagnosed cases. Hepatic lesions were found in four cases which were determined during the histologic examination. CONCLUSION: Ultrasonographic findings of MGS allow for diagnosis of the most cases. However autopsy may be valuable for confirmation of the diagnosis and to evaluate the recurrence risk in future pregnancies.
Prenatal Diagnosis of Meckel–Gruber Syndrome in a Pregnancy Obtained With ICSI
Journal of Assisted Reproduction and Genetics, 2006
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). KEY WORDS: ICSI; Meckel-Gruber syndrome; prenatal diagnosis.
Meckel-Gruber syndrome: Antenatal diagnosis and ethical perspectives
Sudanese journal of paediatrics, 2012
Meckel-Gruber syndrome (MGS) is an autosomal recessive disorder characterized by occipital encephalocele, polycystic kidneys and variable other congenital malformations. We report on a Sudanese patient with MGS diagnosed by antenatal ultrasound scan. Pregnancy was terminated at 25 weeks of gestation.
Pakistan Journal of Medical Sciences, 2012
Meckel-Gruber Syndrome (MKS) is a rare, autosomal recessive genetic disorder, incompatible with life. It is characterized by enlarged polycystic kidneys and post axial polydactyly. Foetal or neonatal death is caused by pulmonary hypoplasia. We report a case of a 35 year old woman who presented at 7 weeks of gestation of her sixth pregnancy. A transabdominal anomaly ultrasound performed for her current pregnancy at 18 weeks of gestation showed features consistent with MKS. The termination of pregnancy was declined and a live newborn female was delivered via an emergency caeserean section at 34 weeks of gestation due to previous history of lower segment caesarean section (LSCS) & leaking. Physical examination of the neonate confirmed the features of MKS. The neonate died within 4-5 hours of birth. This case represented a second trimester diagnosis of a recurrent case of MKS in a non-consanguineous marriage.
Meckel Gruber Syndrome: Case Report
Introduction: Meckel-Gruber Syndrome was first described by J R Meckel in 1822. It is an autosomal recessive disorder, and is caused by the failure of mesodermal induction. The typical triad of Meckel-Gruber Syndrome (MGS) involves meningo-encephalocele, polycystic kidneys and postaxial polydactyly. The worldwide incidence varies from 1 in 1.300 to 1 in 140.000 live births. Case: In this report, we present a case of MGS in which the diagnosis was made at 19 weeks of gestation based on ultrasonographic findings of the typical triad of the disease (encephalocele, polycystic kidneys, and polydactyly) These features were suggestive of the diagnosis of Meckel Gruber Syndrome (MGS). She had also placenta previa totalis. The patient was counselled regarding the lethal outcome of MGS. Unfortunately, the family did not approve the termination of pregnancy. At the 32nd week, she referred to hospital with complaints of vaginal bleeding and uterine contractions. An emergency cesarean section was perfomed due to plasental malposition. A 1380 gr, female fetus was delivered. First and 5th minute Apgar scores were 1 and 0, respectively. Consequently, the baby died after 45 minutes of neonatal resuscitation. Conclusıon: MGS is a lethal disorder. One cannot speak about survival of the fetus because of the pulmonary hypoplasia. The parents should be counseled about prognosis of the fetus and the outcome. Counselers should strictly give information about the recurrence risk for the next pregnancies.
Prenatal Diagnosis, 2018
Objectives: Several small studies have shown that exome sequencing, whole exome (WES) or using a clinically focused panel, increases the diagnostic yield in structurally abnormal fetuses with a normal microarray result. Series using a multidisciplinary team, including clinical geneticists, to identify fetuses with a high likelihood of a genetic aetiology, report diagnostic rates of up to 80%. In the PAGE study, we are prospectively sequencing fetus-parent trios in unselected pregnancies complicated by any fetal abnormality to determine the diagnostic yield in different categories of clinical findings. Recruitment ends in March 2018, and we will aim to report the findings to date. Methods: Parents choosing invasive testing following sonographic detection of any unexpected fetal abnormality and normal chromosomal analysis were consented for WES of excess fetal sample and parental DNA. Expert genetic or fetal medicine review was not performed. Anomalies are classified by system (Table) and, except for increased nuchal translucency, exclude minor sonographic markers. Trio WES is conducted after pregnancy and potential variants identified by analysis of targeted genes. Pathogenicity is assigned after consideration of fetal phenotypes by our clinical review panel comprising scientists, geneticists, and fetal medicine specialists. Causative pathogenic variants are validated. Results explaining the phenotype are reported to parents. Results: Currently, we have recruited 1318 families, of whom 783 with normal chromosomal analysis were eligible. Sequencing is ongoing with results available in 506 (Table). Overall, a diagnostic genetic abnormality was identified in 41/506 cases (8•1%), and a further 15 (3%) had a variant of uncertain significance (VUS) with potential clinical utility. Highest diagnostic yields were found in fetuses with multisystem (16%), cardiac (13.6%), and skeletal anomalies (12.5%). Diagnostic variants were only identified in two (2.1%) fetuses with isolated increased nuchal translucency (>4.0 mm). Conclusions: The PAGE study be will complete this spring, and results to date are showing that WES with variant calling using a focused clinical panel facilitates genetic diagnosis in abnormal fetuses. The overall detection rate of 8.1% in this unselected cohort is lower than that reported by previous smaller-scale studies of cases sequenced after genetic review. Trio sequencing is likely to be needed to deliver results in a timely fashion within pregnancy. Currently, this remains expensive, and our large study is enabling identification of the clinical subgroups most likely to benefit from WES, thereby aiding cost-effective implementation into routine clinical practice. T-1 Table.
Prenatal diagnosis--principles of diagnostic procedures and genetic counseling
Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society, 2007
The frequency of inherited malformations as well as genetic disorders in newborns account for around 3-5%. These frequency is much higher in early stages of pregnancy, because serious malformations and genetic disorders usually lead to spontaneous abortion. Prenatal diagnosis allowed identification of malformations and/or some genetic syndromes in fetuses during the first trimester of pregnancy. Thereafter, taking into account the severity of the disorders the decision should be taken in regard of subsequent course of the pregnancy taking into account a possibilities of treatment, parent's acceptation of a handicapped child but also, in some cases the possibility of termination of the pregnancy. In prenatal testing, both screening and diagnostic procedures are included. Screening procedures such as first and second trimester biochemical and/or ultrasound screening, first trimester combined ultrasound/biochemical screening and integrated screening should be widely offered to preg...
Meckel-Gruber syndrome: a rare and lethal foetal anomaly
International Journal of Reproduction, Contraception, Obstetrics and Gynecology, 2020
Meckel-Gruber syndrome (MGS) is a rare and lethal autosomal recessive disorder characterized by occipital encephalocele, postaxial polydactyly and bilateral dysplastic cystic kidneys. It can be associated with many other congenital malformations. The incidence of Meckel-Gruber syndrome ranges between 1 in 13,000 to 4,00,000 live births. Antenatal ultrasound examination establishes the diagnosis by identifying at least two of the major features. A case is presented that describes a baby with ambiguous genitalia, who presented with the triad of Meckel-Gruber syndrome. The baby died shortly after birth.