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Meckel-Gruber syndrome

MedGen UID:
120513
•Concept ID:
C0265215
•
Disease or Syndrome
Synonyms: Dysencephalia splachnocystica; DYSENCEPHALIA SPLANCHNOCYSTICA; Gruber syndrome; Meckel Syndrome
SNOMED CT: Meckel-Gruber syndrome (29076005); Dysencephalia splanchnocystica (29076005)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (Orphanet)
 
Related genes: TMEM67, B9D2, CEP290, TCTN2, CC2D2A, MKS1, TMEM216, B9D1, NPHP3, RPGRIP1L
 
Monarch Initiative: MONDO:0018921
OMIM® Phenotypic series: PS249000
Orphanet: ORPHA564

Definition

A rare, lethal, genetic, multiple congenital anomaly disorder characterized by the triad of brain malformation (mainly occipital encephalocele), large polycystic kidneys, and polydactyly, as well as associated abnormalities that may include cleft lip/palate, cardiac and genital anomalies, central nervous system (CNS) malformations, liver fibrosis, and bone dysplasia. [from ORDO]

Professional guidelines

PubMed

Diagnosis and Management of Renal Cystic Disease of the Newborn: Core Curriculum 2021.
Raina R, Chakraborty R, Sethi SK, Kumar D, Gibson K, Bergmann C
Am J Kidney Dis 2021 Jul;78(1):125-141. Epub 2021 Jan 6 doi: 10.1053/j.ajkd.2020.10.021. PMID: 33418012
Prenatal diagnosis and clinical significance of cephalocele-A single institution experience and literature review.
Dąbkowska S, Kucińska-Chahwan A, Beneturska A, Ilnicka A, Nowakowska B, Panek G, Roszkowski T, Bijok J
Prenat Diagn 2020 Apr;40(5):612-617. Epub 2020 Feb 12 doi: 10.1002/pd.5654. PMID: 32003477
Meckel-Gruber syndrome: pathologic manifestations, minimal diagnostic criteria, and differential diagnosis.
Alexiev BA, Lin X, Sun CC, Brenner DS
Arch Pathol Lab Med 2006 Aug;130(8):1236-8. doi: 10.5858/2006-130-1236-MS. PMID: 16879033

Recent clinical studies

Etiology

Molecular Diagnostics of Ciliopathies and Insights Into Novel Developments in Diagnosing Rare Diseases.
Modarage K, Malik SA, Goggolidou P
Br J Biomed Sci 2022;79:10221. Epub 2022 Jan 10 doi: 10.3389/bjbs.2021.10221. PMID: 35996505Free PMC Article
Ciliopathies and the Kidney: A Review.
McConnachie DJ, Stow JL, Mallett AJ
Am J Kidney Dis 2021 Mar;77(3):410-419. Epub 2020 Oct 9 doi: 10.1053/j.ajkd.2020.08.012. PMID: 33039432
Prenatal diagnosis and clinical significance of cephalocele-A single institution experience and literature review.
Dąbkowska S, Kucińska-Chahwan A, Beneturska A, Ilnicka A, Nowakowska B, Panek G, Roszkowski T, Bijok J
Prenat Diagn 2020 Apr;40(5):612-617. Epub 2020 Feb 12 doi: 10.1002/pd.5654. PMID: 32003477
Hepatorenal fibrocystic diseases in children.
Park E, Lee JM, Ahn YH, Kang HG, Ha II, Lee JH, Park YS, Kim NK, Park WY, Cheong HI
Pediatr Nephrol 2016 Jan;31(1):113-9. Epub 2015 Aug 11 doi: 10.1007/s00467-015-3185-4. PMID: 26260382
The Meckel-Gruber syndrome protein TMEM67 controls basal body positioning and epithelial branching morphogenesis in mice via the non-canonical Wnt pathway.
Abdelhamed ZA, Natarajan S, Wheway G, Inglehearn CF, Toomes C, Johnson CA, Jagger DJ
Dis Model Mech 2015 Jun;8(6):527-41. Epub 2015 Apr 7 doi: 10.1242/dmm.019083. PMID: 26035863Free PMC Article

Diagnosis

Molecular Diagnostics of Ciliopathies and Insights Into Novel Developments in Diagnosing Rare Diseases.
Modarage K, Malik SA, Goggolidou P
Br J Biomed Sci 2022;79:10221. Epub 2022 Jan 10 doi: 10.3389/bjbs.2021.10221. PMID: 35996505Free PMC Article
Fetal ciliopathies: a retrospective observational single-center study.
Simonini C, Floeck A, Strizek B, Mueller A, Gembruch U, Geipel A
Arch Gynecol Obstet 2022 Jul;306(1):71-83. Epub 2021 Oct 1 doi: 10.1007/s00404-021-06265-7. PMID: 34596737Free PMC Article
Diagnosis and Management of Renal Cystic Disease of the Newborn: Core Curriculum 2021.
Raina R, Chakraborty R, Sethi SK, Kumar D, Gibson K, Bergmann C
Am J Kidney Dis 2021 Jul;78(1):125-141. Epub 2021 Jan 6 doi: 10.1053/j.ajkd.2020.10.021. PMID: 33418012
Meckel-Gruber Syndrome: a population-based study on prevalence, prenatal diagnosis, clinical features, and survival in Europe.
Barisic I, Boban L, Loane M, Garne E, Wellesley D, Calzolari E, Dolk H, Addor MC, Bergman JE, Braz P, Draper ES, Haeusler M, Khoshnood B, Klungsoyr K, Pierini A, Queisser-Luft A, Rankin J, Rissmann A, Verellen-Dumoulin C
Eur J Hum Genet 2015 Jun;23(6):746-52. Epub 2014 Sep 3 doi: 10.1038/ejhg.2014.174. PMID: 25182137Free PMC Article
Earliest ultrasound findings and description of splicing mutations in Meckel-Gruber syndrome.
Eckmann-Scholz C, Jonat W, Zerres K, Ortiz-Brüchle N
Arch Gynecol Obstet 2012 Oct;286(4):917-21. Epub 2012 Jun 15 doi: 10.1007/s00404-012-2411-6. PMID: 22699515

Therapy

Functional validation of novel MKS3/TMEM67 mutations in COACH syndrome.
Lee SH, Nam TS, Li W, Kim JH, Yoon W, Choi YD, Kim KH, Cai H, Kim MJ, Kim C, Choy HE, Kim N, Chay KO, Kim MK, Choi SY
Sci Rep 2017 Aug 31;7(1):10222. doi: 10.1038/s41598-017-10652-z. PMID: 28860541Free PMC Article

Prognosis

Prenatal diagnosis and clinical significance of cephalocele-A single institution experience and literature review.
Dąbkowska S, Kucińska-Chahwan A, Beneturska A, Ilnicka A, Nowakowska B, Panek G, Roszkowski T, Bijok J
Prenat Diagn 2020 Apr;40(5):612-617. Epub 2020 Feb 12 doi: 10.1002/pd.5654. PMID: 32003477
Hepatorenal fibrocystic diseases in children.
Park E, Lee JM, Ahn YH, Kang HG, Ha II, Lee JH, Park YS, Kim NK, Park WY, Cheong HI
Pediatr Nephrol 2016 Jan;31(1):113-9. Epub 2015 Aug 11 doi: 10.1007/s00467-015-3185-4. PMID: 26260382
CEP290, a gene with many faces: mutation overview and presentation of CEP290base.
Coppieters F, Lefever S, Leroy BP, De Baere E
Hum Mutat 2010 Oct;31(10):1097-108. doi: 10.1002/humu.21337. PMID: 20690115
The ciliopathies: an emerging class of human genetic disorders.
Badano JL, Mitsuma N, Beales PL, Katsanis N
Annu Rev Genomics Hum Genet 2006;7:125-48. doi: 10.1146/annurev.genom.7.080505.115610. PMID: 16722803
Meckel-Gruber syndrome.
Gazioğlu N, Vural M, Seçkin MS, Tüysüz B, Akpir E, Kuday C, Ilikkan B, Erginel A, Cenani A
Childs Nerv Syst 1998 Mar;14(3):142-5. doi: 10.1007/s003810050198. PMID: 9579873

Clinical prediction guides

Aberrant Wnt signalling and cellular over-proliferation in a novel mouse model of Meckel-Gruber syndrome.
Wheway G, Abdelhamed Z, Natarajan S, Toomes C, Inglehearn C, Johnson CA
Dev Biol 2013 May 1;377(1):55-66. Epub 2013 Feb 27 doi: 10.1016/j.ydbio.2013.02.015. PMID: 23454480
The ciliary transitional zone and nephrocystins.
Shiba D, Yokoyama T
Differentiation 2012 Feb;83(2):S91-6. Epub 2011 Dec 12 doi: 10.1016/j.diff.2011.11.006. PMID: 22169048
CEP290, a gene with many faces: mutation overview and presentation of CEP290base.
Coppieters F, Lefever S, Leroy BP, De Baere E
Hum Mutat 2010 Oct;31(10):1097-108. doi: 10.1002/humu.21337. PMID: 20690115
Omphalocele and gastroschisis and associated malformations.
Stoll C, Alembik Y, Dott B, Roth MP
Am J Med Genet A 2008 May 15;146A(10):1280-5. doi: 10.1002/ajmg.a.32297. PMID: 18386803
The ciliopathies: an emerging class of human genetic disorders.
Badano JL, Mitsuma N, Beales PL, Katsanis N
Annu Rev Genomics Hum Genet 2006;7:125-48. doi: 10.1146/annurev.genom.7.080505.115610. PMID: 16722803

Recent systematic reviews

Neurosurgical intervention for the Meckel-Gruber Syndrome: A systematic review.
Junior JHMF, Junior SP, Pustilnik HN, de Almeida Leão L, da Paz MGDS, Araujo TB, de Deus FOG, Alcântara T, Dourado JC, de Avellar LM
Childs Nerv Syst 2024 Jul;40(7):2161-2168. Epub 2024 Mar 9 doi: 10.1007/s00381-024-06346-3. PMID: 38459147

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