Meckel – Gruber syndrome is a severe autosomal – recessive condition, affecting multiple organs and most often lethal within the first days of life. Its incidence ranges between 1:13.500 and 1:40.000 live births. Typical clinical signs are an occipital encephalocele, microphthalmia, bilateral dysplastic cystic kidneys and other malformations of the CNS. Further MKS can be associated with polydactyly, situs inversus, biliary duct proliferation and pulmonary hypoplasia. Most of these changes can be detected before the 14th week of gestation leading to termination of pregnancy.
Different ciliary genes could be identified as responsible for MKS. There is a significant genetic and clinical overlap with other ciliopathies as the Joubert syndrome or Nephronophthisis. A correlation between type of underlying mutation and severity of disease could be found for some genes. Due to high phenotypic variability even within families, effects of additional genetic modifiers are highly discussed.Meckel – Gruber syndrome – summary
|manifestation||antenatal. A typical trias of malformation of kidneys, CNS and extremities allows a diagnosis before 14th week of gestation.|
|frequency||highly variable: 1:13.500 (Massachusetts), 1 : 140.000 (Great Britain), Finland 1 : 8.500|
|inheritance||autosomal – recessive|
|pathogenesis||All genes encode for proteins of the primary cilium. The exact pathomechanism remains to be elucidated.|
|progress and prognosis||High rates of intrauterine death. Live births die within the first hours or days of life.|
Meckel - Gruber Syndrom genes known to date
|Disease||OMIM Phenotype Nr||Gene||OMIM – Gene number||alternative Phenotype + OMIM Phenotype Nr|
|13||Meckel/Joubert Phänotyp||617562||TMEM 237||614423||JBTS29||617562|
- Barker AR, Thomas R, Dawe HR. Meckel-Gruber syndrome and the role of primary cilia in kidney, skeleton, and central nervous system development. Organogenesis. 2014;10:96–107.
- Huber C, Cormier-Daire V. Ciliary disorder of the skeleton. Am J Med Genet C Semin Med Genet. 2012;160C:165–74.