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Meckel syndrome

Thursday 18 March 2004

Meckel syndrome is an autosomal recessive disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly.

Meckel-Gruber syndrome (MKS) (OMIM 24900) is a lethal, rare, autosomal recessive condition mapped to chromosomes 17q21-24, 11q13, and 8q24.

This mapping suggests genetic heterogeneity in MKS. The triad of occipital encephalocele, large polycystic kidneys, and postaxial polydactyly characterizes MKS. Associated abnormalities include oral clefting, genital anomalies, CNS malformations, and liver fibrosis.

Pulmonary hypoplasia is the leading cause of death. Improvements in ultrasonography have enabled prenatal diagnosis as early as 10 weeks’ gestation.

Failure of mesodermal induction has been suggested to cause MKS. The induction cascades of early morphogenesis involve numerous growth factors, homeo box genes, and paired domain genes.


- variable prenatal growth deficiency

- craniofacial anomalies

- cardiac anomalies

  • cardiac septal defects
  • coarctation of aorta
  • patent ductus arteriosus

- cleft epiglottis

- hepatic anomalies (20%) (11000335)

  • intrahepatic bile duct anomalies
  • ductal plate malformation (DPM) (congenital hepatic fibrosis)
  • reactive biliary neoductules proliferation (reactive bile duct proliferation)
  • bile duct dilatation
  • arrested development of the intrahepatic biliary system (biliary cylinders)
  • reactive portal fibrosis
  • portal fibrous vascular obliteration

- splenic anomalies

- single umbilical artery
- omphalocele

- digestive anomalies

- genital anomaies

- renal anomalies

- hypoplastic bladder
- limb anomalies

- nervous system anomalies

- adrenal hypoplasia
- breech presentation
- perinatal death
- placental enlargement


Several loci for Meckel syndrome have been mapped:

- MKS1 : mutation in gene MKS1 on 17q21-q24, encoding a component of the flagellar apparatus basal body proteome (MIM.609883).
- MKS2 (MIM.603194) on 11q
- MKS3 on 8q : germline mutation in gene TMEM67 encoding the transmembrane protein meckelin (MIM.609884)
- MKS4 : CEP290 (NPHP6) germline mutations (17564974)

Differential diagnosis

- Bardet-Bield syndrome (BBS)
- hydrolethalus syndrome (MIM.236680)

Case records

- Case #10136
- Case #11132

Differential diagnosis

- Bardet-Bield syndrome (BBS)
- Goldston syndrome
- Miranda syndrome


- Baala L, Audollent S, Martinovic J, Ozilou C, Babron MC, Sivanandamoorthy S, Saunier S, Salomon R, Gonzales M, Rattenberry E, Esculpavit C, Toutain A, Moraine C, Parent P, Marcorelles P, Dauge MC, Roume J, Merrer ML, Meiner V, Meir K, Menez F, Beaufrere AM, Francannet C, Tantau J, Sinico M, Dumez Y, Macdonald F, Munnich A, Lyonnet S, Gubler MC, Genin E, Johnson CA, Vekemans M, Encha-Razavi F, Attie-Bitach T. Pleiotropic Effects of CEP290 (NPHP6) Mutations Extend to Meckel Syndrome. Am J Hum Genet. 2007 Jul;81(1):170-9. PMID: 17564974

- Karmous-Benailly H, Martinovic J, Gubler MC, Sirot Y, Clech L, Ozilou C, Auge J, Brahimi N, Etchevers H, Detrait E, Esculpavit C, Audollent S, Goudefroye G, Gonzales M, Tantau J, Loget P, Joubert M, Gaillard D, Jeanne-Pasquier C, Delezoide AL, Peter MO, Plessis G, Simon-Bouy B, Dollfus H, Le Merrer M, Munnich A, Encha-Razavi F, Vekemans M, Attie-Bitach T. Antenatal presentation of bardet-biedl syndrome may mimic meckel syndrome. Am J Hum Genet. 2005 Mar;76(3):493-504. PMID: 15666242

- Sergi C, Adam S, Kahl P, Otto HF. Study of the malformation of ductal plate of the liver in Meckel syndrome and review of other syndromes presenting with this anomaly. Pediatr Dev Pathol. 2000 Nov-Dec;3(6):568-83. PMID: 11000335

- Blankenberg, T. A.; Ruebner, B. H.; Ellis, W. G.; Bernstein, J.; Dimmick, J. E. : Pathology of renal and hepatic anomalies in Meckel syndrome. Am. J. Med. Genet. Suppl. 3: 395-410, 1987.


- Katsanis N. Ciliary proteins and exencephaly. Nat Genet. 2006 Feb;38(2):135-6. PMID: 16444248

- Hildebrandt F, Otto E. Cilia and centrosomes: a unifying pathogenic concept for cystic kidney disease? Nat Rev Genet. 2005 Dec;6(12):928-40. PMID: 16341073

- Johnson CA, Gissen P, Sergi C. Molecular pathology and genetics of congenital hepatorenal fibrocystic syndromes. J Med Genet. 2003 May;40(5):311-9. PMID: 12746391

- Salonen R, Paavola P. Meckel syndrome. J Med Genet. 1998 Jun;35(6):497-501. PMID: 9643292