Search :     
Articles » Syndromes » Meckel Gruber syndrome

1994-09-15-12 Meckel syndrome, first trimester diagnosis © Weinstein

Meckel syndrome, first trimester diagnosis

Barbara J. Weinstein, MD, Beryl R. Benacerraf*, MD

*333 Longwood Avenue Boston, MA 02115 Ph: 617-739-0245 Fax: 617-738-6703.

Synonym: Dysencephalia splanchnocysticia.

Definition: A syndrome characterized by posterior encephalocele (80%), polydactyly (75%), and cystic dysplasia of the kidneys (95%). Other associated abnormalities include heart, liver, genital, and facial defects.

Prevalence: Unknown, although it is estimated that Meckel-Gruber syndrome may account for 5% of all neural tube defects.

Etiology: Autosomal recessive inheritance.

Pathogenesis: Unknown, although the similarities in phenotype with trisomy 13 have led to speculation that a defect on chromosome 13 may be involved.

Associated anomalies: Micrognathia, hypopituitarism, cardiac and genital anomalies, short-webbed neck, hepatic fibrosis, accessory spleens, syndactyly, clinodactyly, clubbed foot, cleft lip and palate.

Differential diagnosis: Trisomy 13 is the most likely syndrome and has virtually the same findings as Meckel-Gruber syndrome. Any fetus, however, with a neural tube defect (particularly an encephalocele) can be considered as a possible Meckel-Gruber syndrome, particularly if the kidneys are abnormal.

Prognosis: Lethal.

Recurrence risk: 25%.

Management: Pregnancy termination before viability.

MESH Encephalocele complications; hand-abnormalities; Kidneys-polycystic-diagnosis BDE 0634 ICD9 759.8 POS 3287 MIM 249000 CDC 759.890


Meckel-Gruber syndrome was first described by Meckel in 1898 and later by Gruber as a syndrome characterized by a posterior encephalocele, postaxial polydactyly, and cystic, dysplastic kidneys1. Although other abnormalities, including heart, genital, facial, and limb defects can also be seen, the triad of encephalocele, polydactyly, and large, echogenic kidneys seen prenatally should suggest the diagnosis of Meckel-Gruber syndrome2-5.

Because this disorder is autosomal recessive, families with  previously affected children stand a 25% chance of recurrence in future pregnancies2. Prenatal diagnosis, therefore, has been extremely important for those families, and expectant mothers are anxious for the earliest possible detection3-5.

We report a case in which the diagnosis of Meckel-Gruber syndrome was possible by transvaginal sonography in the first trimester, in a family with a previously affected child.

Case report

A 36-year-old patient presented for sonography at 11 weeks because of a history of Meckel-Gruber syndrome. She had three living daughters, one of which was a surviving twin from a pregnancy six years ago where the co-twin had Meckel-Gruber syndrome. The diagnosis had been made sonographically at 21 weeks in the presenting twin who had a posterior encephalocele, bilaterally enlarged and echogenic kidneys, polydactyly, and a severe cardiac abnormality with a single ventricle. The twin pregnancy went to term, and the patient gave birth to a normal female child and a child with classic findings of Meckel-Gruber syndrome. The affected child expired shortly after birth.

During the current pregnancy, an 11-week transvaginal sonogram demonstrated an encephalocele involving the posterior fossa with a large posterior fossa cyst protruding from the occiput. The kidneys were echogenic, suggesting cystic dysplasia, and there was evidence of polydactyly of the hands. Based on these findings, the diagnosis of Meckel­Gruber recurrence was made. The patient elected to terminate the pregnancy, and the diagnosis was confirmed after delivery.

Figure 1: Transabdominal view of the fetus at 11.7 weeks, showing evidence of a posterior encephalocele with a cystic component protruding from the outline of the skull.

Figure 2: Transvaginal scan of the fetal cranium, showing an irregular cystic area (arrows) with protrusion of the cystic area posteriorly, consistent with an encephalocele.

Figure 3: Transvaginal scan of the fetal hand, showing polydactyly.


Meckel-Gruber syndrome can be associated with a wide variety of abnormalities, although the classic triad includes neural tube defects, particularly occipital encephalocele (80%); polydactyly (75%); and cystic dysplasia of the kidneys (95%)3. Other abnormalities which can occur in association with the syndrome and which may be detectable sonographically include micrognathia, cardiac abnormalities, syndactyly, clinodactyly, and clubbed foot3.Since one of the most constant features of Meckel-Gruber syndrome is a neural tube defect, it is possible to overlook the diagnosis of Meckel-Gruber syndrome in a fetus with a neural tube defect and therefore underestimate the recurrence risk for the family3,5. Recurrence of a neural tube defect may be between 1% and 3% in a given family, whereas recurrence of Meckel­Gruber syndrome is as high as 25%, due to its autosomal recessive inheritance pattern. It is estimated that Meckel-Gruber syndrome accounts for 5% of all neural tube defects3,4. Therefore, when an occipital encephalocele is encountered (particularly prenatally), it is important to examine the remainder of the fetus for other abnormalities such as polydactyly and cystic dysplasia of the kidneys, so that the proper diagnosis can be made. This case is also unique in that the diagnosis was made in spite of the absence of oligohydramnios, which is a classical finding. In the current case, the family history of a previous affected child made the diagnosis possible in the first trimester. The differential diagnosis varies according to the types of abnormalities in any given case of Meckel-Gruber syndrome. The most likely syndrome to be confused with Meckel-Gruber syndrome is trisomy 13, since 30% of fetuses with trisomy 13 will have enlarged, cystic kidneys and many of them will also have polydactyly and neural tube defects3,5. A karyotype, therefore, is important in fetuses with this constellation of physical findings. Although the dismal outcome is the same whether the fetus has, trisomy 13 or Meckel-Gruber syndrome, the recurrence rate is indeed very different, with trisomy 13 being mostly a sporadic event with a rather low recurrence rate versus Meckel-Gruber syndrome with its autosomal recessive pattern.

The management of a pregnancy with Meckel-Gruber syndrome revolves around pregnancy termination if the diagnosis is found prior to 24 weeks and if the patient desires it or very conservative management if the pregnancy continues or if the syndrome is discovered late, so that heroic measures are not attempted for a fetus with a lethal disorder.


1. Meckel JR. Beschreibung zweier durch sehr   alnliche Bildungsaweichung entseller Geschwister. Dtsch Arch Phiol 1898;7:99.

2. Mecke J, Passarge E. Encephalocele, polycystic kidneys and polydactyly as an autosomal recessive trait simulating certain other disorders. Ann Genet 1971;14:97.

3.Nyberg DA, Hallesy D, Mahony BS, et al. Meckel-Gruber syndrome:importance of prenatal diagnosis. J Ultrasound Med 1990 9:691.

4.Pardes JG, Engel IA, Blomquist K, et al. Ultrasonography of intrauterine Meckel"s syndrome. J Ultrasound Med 1984; 3:33.

5.Karjalainen 0, Aula P, Seppala M,  et al. Prenatal diagnosis of the Meckel syndrome. Obstet Gynecol 1981;47:13S.

Help Support :