Meckel-Gruber syndrome (MKS) is a rare lethal autosomal recessive disorder with typical anomalies including encephalocele, multicystic renal dysplasia, congenital liver fibrosis, and polydactyly. MKS is caused by mutations of genes localized on different chromosomes. Karyotypes of published Meckel-Gruber syndrome cases are without any aberrations. We present a male fetus with meningoencephalocele, multicystic renal dysplasia, congenital liver fibrosis, and other anomalies. Standard cytogenetic examination of cultured fetal skin and muscle fibroblasts showed mosaic trisomy 17. Homozygous deletion in CC2D2A gene was found by Sanger sequencing. This is to our knowledge the first case of genetically confirmed Meckel-Gruber syndrome with incidental cofinding of mosaic trisomy 17. Abnormal karyotype does not exclude diagnosis of MKS with risk of recurrence 25% in next pregnancy. In the case of anomalies typical for Meckel-Gruber syndrome, genetic analysis is indicated.

Meckel-Gruber syndrome (MKS, OMIM #607361) is a rare pre- or perinatal lethal autosomal recessive ciliopathy caused by mutations in at least 12 known genes. It has a clinical and genetic overlap with other viable ciliopathies, especially Joubert syndrome and Joubert syndrome-related disorders. MKS is characterized by multicystic kidney dysplasia, central nervous system malformations (usually occipital encephalocele), ductal plate malformation of the liver, and postaxial polydactyly.
We identified a homozygous mutation in TMEM67 (MKS3) in a fetus affected by MKS; however, only the mother was a carrier of the respective mutation. Genotyping with polymorphic microsatellite markers and single nucleotide polymorphism (SNP) array revealed a maternal uniparental disomy (UPD) of the entire chromosome 8 (upd(8)mat), harboring TMEM67.
This is the first reported case of UPD as a cause of MKS. The possible underlying mechanisms for uniparental disomy (UPD) are reviewed. Even if rare, awareness of UPD and comprehensive work-up in the case of unexpected homozygosity for a recessive mutation is essential for accurate genetic counseling and assessment of the risk of recurrence.