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. For a more ... 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. For a more complete phenotypic description and information on genetic heterogeneity, see MKS1 (249000). Morgan et al. (2002) stated that comparison of the clinical features of MKS3-linked cases with reports of MKS1- and MKS2 (603194)-linked kindreds suggested that polydactyly (and possibly encephalocele) are less common in MKS3-linked families. Consugar et al. (2007) observed that polydactyly and occipital encephalocele were less common in MKS3 compared to MKS1.
Smith et al. (2006) sequenced the human ortholog of rat Wpk, TMEM67 (609884), and found different pathogenic mutations in 5 MKS3 families. Consistent with the consanguineous nature of these families, all the mutations were homozygous.
Consugar ... Smith et al. (2006) sequenced the human ortholog of rat Wpk, TMEM67 (609884), and found different pathogenic mutations in 5 MKS3 families. Consistent with the consanguineous nature of these families, all the mutations were homozygous. Consugar et al. (2007) identified 7 novel pathogenic mutations in the TMEM67 gene (see, e.g., 609884.0011) in 5 of 17 families with a clinical diagnosis of Meckel syndrome. All 5 families were of European origin. In a patient from a consanguineous family who presented with MKS3 and cerebellar heterotopia, Adams et al. (2012) identified a homozygous deletion in the C-terminal region of meckelin (609884.0025). The deletion abrogated the interaction of meckelin with filamin A (FLNA; 300017), resulting in aberrant hyperactivation of canonical Wnt signaling in patient fibroblasts compared with controls.