Meckel-Gruber Syndrome Workup

Updated: Jul 28, 2017
  • Author: Parul Bhagwati Jayakar, MD, MS, FACMG; Chief Editor: Luis O Rohena, MD, FAAP, FACMG  more...
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Laboratory Studies

Alpha-fetoprotein (AFP) level from either maternal blood or amniotic fluid may help to detect an encephalocele in patients with Meckel-Gruber syndrome (MGS) (although most encephaloceles are closed and do not elevate AFP levels). AFP can be measured in amniotic fluid after about 12 weeks' gestation and in maternal blood after about 15 weeks' gestation.

Chromosome analysis

See the list below:

  • Chromosome analysis is essential to exclude trisomy 13, which Meckel-Gruber syndrome mimics. Trisomy 13 carries a 1% recurrence risk, as opposed to the 25% recurrence rate for Meckel-Gruber syndrome. Linkage or mutation analysis is not yet available.
  • If anomalies are detected early in the first trimester, chorionic villus sampling (CVS) can be performed at 10-12 weeks' gestation or later in pregnancy if oligohydramnios does not permit amniocentesis.
  • Amniocentesis is performed after 14 weeks’ gestation if an adequate fluid pocket is present.
  • Tests can be done to assess prenatal diagnosis, linkage, as well as carrier testing.

Table. Chromosomal Markers for Meckel Gruber Syndrome (Open Table in a new window)

Protein Name Locus Name Gene Chromosomal Locus
Meckel syndrome type 1 protein MKS1 MKS1 17q23
... MKS2 TMEM216 11q13
Meckelin MKS3 TMEM67 8q21.1-q22.1
... MKS4 CEP290 12q21.3
Protein fantom MKS5 RPGRIP1L 16q12.2
Coiled-coil and C2 domain-containing protein 2A MKS6 CC2D2a 4p15.3
... MKS7 NPHP3 3q22.1
... MKS8 TCTN2 12q24.31
... MKS9 B9D1 17p11.2
... MKS10 B9D2 19q13.2
... MKS11 TMEM231 16q23.1
... MKS12 KIF14 1q32.1

Imaging Studies

Prenatal ultrasonography

See the list below:

  • Prenatal ultrasound is currently the best method available to diagnose Meckel-Gruber syndrome and is available in 2-dimensional (2D), 3-dimensional (3D), and 4-dimensional (4D) modalities; 4D is particularly useful in assessing facial features and deformities, musculoskeletal malformations, and limitation of movement. [28, 29]
  • The second trimester is the usual time of diagnosis; however, with a skilled operator, first-trimester diagnosis may be possible for both high-risk and low-risk families.
  • Color Doppler can be used to assess for lung perfusion in the last trimester, to search for the presence of renal arteries in cases of oligohydramnios, (suspected renal agenesis or hypoplasia), and also to assess flow in the umbilical arteries.
  • Diagnosis in the second trimester becomes more difficult when oligohydramnios secondary to poor renal output impairs visualization.
  • Occipital encephalocele is easily visualized beginning in late first trimester. Part of the brain and meninges protrude through the skull defect.
  • Large, cystic, echogenic kidneys are a consistent ultrasonographic finding, although oligohydramnios can obscure detection of renal dysplasia. Experienced ultrasonographers may be able to detect polydactyly in the second trimester if oligohydramnios is not present.


See the list below:

  • MRI is a valuable complement to ultrasonography in assessing fetal anomalies in the presence of severe oligohydramnios.
  • It is mainly used when ultrasonography findings are inconclusive or are insufficient to guide treatment choices.
  • It is useful in detecting origin and extent of an abnormality but must be performed after 18 weeks' gestation.
  • It is superior to ultrasonography in detecting CNS abnormalities that are commonly found in Meckel-Gruber syndrome but is limited in that it cannot be used to assess fetal movement.
  • MRI can reveal renal size and occipital defects, such as encephaloceles.

Histologic Findings

See the list below:

  • The primary renal abnormality appears to be failed interaction of the metanephric duct and renal blastema. The kidneys, therefore, show little corticomedullary differentiation, and the nephrons are severely deficient, causing enlargement of the kidneys. Thin-walled cysts appear throughout the parenchyma.
  • Hepatic lesions can be considered one of the hidden abnormalities of Meckel-Gruber syndrome because they are visible only during postmortem examination. Development arrests at the stage of bilaminar plates, which become atrophic during normal development. In Meckel-Gruber syndrome, the plates do not atrophy and prevent reorganization by the remaining biliary cells to form tubular ducts. The resultant fibrosis can be severe enough to occlude portal veins. Bile canaliculi are smaller and less well developed and have inspissated bile within the abnormal ductules.