eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Genetics

Meckel-Gruber Syndrome: Differential Diagnoses & Workup

Author: Suzanne M Carter, MS, Senior Genetic Counselor, Associate, Department of Obstetrics and Gynecology, Division of Reproductive Genetics, Montefiore Medical Center, Albert Einstein College of Medicine
Coauthor(s): Susan J Gross, MD, FRCS(C), FACOG, FACMG, Codirector, Division of Reproduction Genetics, Associate Professor, Department of Obstetrics and Gynecology, Albert Einstein College of Medicine
Contributor Information and Disclosures

Updated: May 15, 2007

Differential Diagnoses

Smith-Lemli-Opitz Syndrome

Other Problems to Be Considered

Hydrocephalus
Meckel syndrome type 2
Trisomy 13

Workup

Laboratory Studies

  • Chromosome analysis

    • Chromosome analysis is essential to exclude trisomy 13, which Meckel-Gruber syndrome (MKS) mimics. Trisomy 13 carries a 1% recurrence risk, as opposed to the 25% recurrence rate for MKS. 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.

Imaging Studies

  • Prenatal ultrasonography  

    • Prenatal ultrasonography is currently the best method available to diagnose MKS.
    • 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.
    • 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.
  • MRI 

    • MRI is a valuable complement to ultrasonography in assessing fetal anomalies in the presence of severe oligohydramnios.
    • MRI can reveal renal size and occipital defects, such as encephaloceles.

Histologic Findings

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 MKS because they are visible only during postmortem examination. Development arrests at the stage of bilaminar plates, which atrophy during normal development. In MKS, 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.

More on Meckel-Gruber Syndrome

Overview: Meckel-Gruber Syndrome
Differential Diagnoses & Workup: Meckel-Gruber Syndrome
Treatment & Medication: Meckel-Gruber Syndrome
Follow-up: Meckel-Gruber Syndrome
References
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References

  1. Ahdab-Barmada M, Claassen D. A distinctive triad of malformations of the central nervous system in the Meckel-Gruber syndrome. J Neuropathol Exp Neurol. Nov 1990;49(6):610-20. [Medline].

  2. Alexiev BA, Lin X, Sun CC. Meckel-Gruber syndrome: pathologic manifestations, minimal diagnostic criteria, and differential diagnosis. Arch Pathol Lab Med. Aug 2006;130(8):1236-8. [Medline].

  3. Blankenberg TA, Ruebner BH, Ellis WG. Pathology of renal and hepatic anomalies in Meckel syndrome. Am J Med Gen. 1987;3:395-410. [Medline].

  4. Farag TI, Usha R, Uma R. - Usha R. Clin Genet. Sep 1990;38(3):176-9. [Medline].

  5. Herman TE, Siegel MJ. Special imaging casebook. Meckel-Gruber syndrome. J Perinatol. Mar-Apr 1996;16(2 Pt 1):144-6. [Medline].

  6. Johnson CA, Gissen P, Sergi C. Molecular pathology and genetics of congenital hepatorenal fibrocystic syndromes. J Med Genet. May 2003;40(5):311-9. [Medline].

  7. Liu SS, Cheong ML, She BQ, Tsai MS. First-trimester ultrasound diagnosis of Meckel-Gruber syndrome. Acta Obstet Gynecol Scand. 2006;85(6):757-9. [Medline].

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  10. Morgan NV, Gissen P, Sharif SM. A novel locus for Meckel-Gruber syndrome, MKS3, maps to chromosome 8q24. Hum Genet. Oct 2002;111(4-5):456-61. [Medline].

  11. Nyberg DA, Hallesy D, Mahony BS. Meckel-Gruber syndrome. Importance of prenatal diagnosis. J Ultrasound Med. Dec 1990;9(12):691-6. [Medline].

  12. Paavola P, Avela K, Horelli-Kuitunen N. High-resolution physical and genetic mapping of the critical region for Meckel syndrome and Mulibrey Nanism on chromosome 17q22-q23. Genome Res. Mar 1999;9(3):267-76. [Medline].

  13. Paavola P, Salonen R, Baumer A. Clinical and genetic heterogeneity in Meckel syndrome. Hum Genet. Nov 1997;101(1):88-92. [Medline].

  14. Paavola P, Salonen R, Weissenbach J. The locus for Meckel syndrome with multiple congenital anomalies maps to chromosome 17q21-q24. Nat Genet. Oct 1995;11(2):213-5. [Medline].

  15. Roume J, Genin E, Cormier-Daire V. A gene for Meckel syndrome maps to chromosome 11q13. Am J Hum Genet. Oct 1998;63(4):1095-101. [Medline].

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  18. Sepulveda W, Sebire NJ, Souka A, Snijders RJ, Nicolaides KH. Diagnosis of the Meckel-Gruber syndrome at eleven to fourteen weeks' gestation. Am J Obstet Gynecol. Feb 1997;176(2):316-9. [Medline].

  19. Yapar EG, Ekici E, Dogan M. Meckel-Gruber syndrome concomitant with Dandy-Walker malformation: prenatal sonographic diagnosis in two cases. Clin Dysmorphol. Oct 1996;5(4):357-62. [Medline].

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Further Reading

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Keywords

Meckel-Gruber syndrome, MKS, occipital encephalocele, large polycystic kidneys, postaxial polydactyly, oral clefting, genital anomalies, CNS malformations, liver fibrosis, pulmonary hypoplasia, oligohydramnios, dysencephalia splanchnocystica, Gruber syndrome, Gruber's syndrome, trisomy 13, Meckel syndrome type 1, MKS1, MES

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Contributor Information and Disclosures

Author

Suzanne M Carter, MS, Senior Genetic Counselor, Associate, Department of Obstetrics and Gynecology, Division of Reproductive Genetics, Montefiore Medical Center, Albert Einstein College of Medicine
Suzanne M Carter, MS is a member of the following medical societies: American Bar Association
Disclosure: Nothing to disclose.

Coauthor(s)

Susan J Gross, MD, FRCS(C), FACOG, FACMG, Codirector, Division of Reproduction Genetics, Associate Professor, Department of Obstetrics and Gynecology, Albert Einstein College of Medicine
Susan J Gross, MD, FRCS(C), FACOG, FACMG is a member of the following medical societies: American College of Medical Genetics, American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, American Medical Association, American Society of Human Genetics, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Medical Editor

Christian J Renner, MD, Consulting Staff, Department of Pediatrics, University Hospital for Children and Adolescents, Erlangen, Germany
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Nothing to disclose.

Managing Editor

Margaret McGovern, MD, PhD, Vice Chair, Professor, Department of Human Genetics, Mount Sinai School of Medicine
Margaret McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics and American Society of Human Genetics
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Clinical Assistant Professor of Pediatrics, University of North Dakota, School of Medicine and Health Sciences; Consulting Staff, Altru Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Bruce A Buehler, MD, Professor, Department of Pathology and Microbiology, Director, Hattie B Munroe Center for Human Genetics, Chairman, Department of Pediatrics, University of Nebraska Medical Center
Bruce A Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

 
 
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