Meckel-Gruber syndrome (MGS) is classically characterized by the triad of:
- renal cystic dysplasia: multiple renal cysts (present most cases)
- occipital encephalocoele/holoprosencephaly (~70%)
- postaxial polydactyly: usually hexadactyly (~65%)
Additional hepatic developmental defects and hepatic fibrosis may occur. A variety of malformations may be associated with this syndrome but most agree that cystic renal dysplasia must be present with at least one of the other two anomalies in the classic "triad".
The incidence is estimated to be 1:30,000. A disproportionately higher prevalence may be present in Finland, Belgium and in some parts of India.
Central nervous system/craniofacial
- fetal ventriculomegaly
- agenesis of corpus callosum
- Dandy-Walker malformation
- cleft lip +/- palate
Cardiac and vascular malformations
- cardiac rotational abnormalities
- ventriculoseptal defect (VSD)
- aortic hypoplasia
- aortic coarctation
- aortic valve stenosis
Meckel-Gruber syndrome shares some features with trisomy 13 and is therefore also termed pseudotrisomy 13 1. Karyotyping is recommended if the above triad is seen on antenatal scanning.
Genetics and inheritance
It is inherited as an autosomal recessive fashion, the risk of the condition affecting a subsequent child is therefore 25% 1. There is genetic heterogeneity with at least three genes (MKS1, MKS2 and MKS3) having been identified 4,7:
- MKS1: on chromosome 17q
- MKS2: on chromosome 11q
- MKS3: on chromosome 8q or 13 q
In addition to the demonstration of the classical features such as an occipital encephalocele, multiple renal cysts and polydactyly, there may be evidence of oligohydramnios (or anhydramnios in severe cases) and microcephaly).
Treatment and prognosis
History and etymology
Meckel-Gruber syndrome is named after:
- Johann Friedrich Meckel (the younger) (1781-1833) German anatomist (also known for Meckel diverticulum) 9
- Georg Gruber (1884-1977) German physician 9: who first described the constellation of findings in 1934, terming it dysencephalia splanchnocystica
Although it was only in 1969 that the moniker "Meckel-Gruber syndrome" was coined by Opitz and Howe 9.
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- 2. Fong KW, Toi A, Salem S et-al. Detection of fetal structural abnormalities with US during early pregnancy. Radiographics. 24 (1): 157-74. doi:10.1148/rg.241035027 - Pubmed citation
- 3. Rypens F, Dubois J, Garel L et-al. Obstetric US: watch the fetal hands. Radiographics. 26 (3): 811-29. doi:10.1148/rg.263055113 - Pubmed citation
- 4. Dawe HR, Smith UM, Cullinane AR et-al. The Meckel-Gruber Syndrome proteins MKS1 and meckelin interact and are required for primary cilium formation. Hum. Mol. Genet. 2007;16 (2): 173-86. doi:10.1093/hmg/ddl459 - Pubmed citation
- 5. Zhou Q, Cardoza JD, Barth R. Prenatal sonography of congenital renal malformations. AJR Am J Roentgenol. 1999;173 (5): 1371-6. AJR Am J Roentgenol (citation) - Pubmed citation
- 6. Ickowicz V, Eurin D, Maugey-laulom B et-al. Meckel-Grüber syndrome: sonography and pathology. Ultrasound Obstet Gynecol. 2006;27 (3): 296-300. doi:10.1002/uog.2708 - Pubmed citation
- 7. Chen CP. Meckel syndrome: genetics, perinatal findings, and differential diagnosis. Taiwan J Obstet Gynecol. 2007;46 (1): 9-14. doi:10.1016/S1028-4559(08)60100-X - Pubmed citation
- 8. Agrwal S, Dabas A, Pal T, Jhamb U. Goldston syndrome with congenital hepatic fibrosis: A rare cause of neonatal cholestasis. (2019) Intractable & rare diseases research. 8 (2): 154-157. doi:10.5582/irdr.2019.01017 - Pubmed
- 9. Janjua RM, Schultka R, Goebbel L, Pait TG, Shields CB. The legacy of Johann Friedrich Meckel the Elder (1724-1774): a 4-generation dynasty of anatomists. (2010) Neurosurgery. 66 (4): 758-70; discussion 770-1. doi:10.1227/01.NEU.0000367997.45720.A6 - Pubmed