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Walker-Warburg syndrome (WWS) is a severe form of congenital muscular dystrophy (CMD) secondary to α-dystroglycanopathy with muscle, brain and eye abnormalities often leading to death in the first weeks of life. It is transmitted in an autosomal recessive pattern, and has been linked to at least fifteen different genes; including protein O-mannosyltransferase 1 (POMT1), protein O-mannosyltransferase 2 (POMT2), protein O-mannose beta-1,2-N acetylglucosaminyltransferase (POMGNT1) gene, the fukutin (FKTN) gene, the fukutin-related protein (FKRP) gene, the LARGE gene, the isoprenoid synthase domain-containing (ISPD) gene and other genes. We report on a family having four consecutive siblings affected by this condition with lethal outcome in three of them, and terminated pregnancy of the fourth based on antenatal fetal MRI complex brain and kidney anomalies that heralded proper and deep clinical phenotyping. The diagnosis of WWS was suggested based on the unique collective phenotype comprising neurological involvement in the form of lissencephaly, subcortical/subependymal heterotopia and cerebellar hypoplasia shared by all four siblings, microphthalmia in one sibling, and large cystic kidneys in the fetus and another sibling. Other unshared neurological abnormalities included hydrocephalus and Dandy-Walker malformation. By whole exome sequencing of the proband fetus, we identified a highly conserved missense mutation in the POMT2 gene that is known to cause congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies, and Walker-Warburg syndrome. In conclusion, the heterogenous clinical presentation in the four affected siblings of this consanguineous family with POMT2 mutation expands the current clinical spectrum of POMT2 associated WWS to include large cystic kidneys; and further confirms intra-familial variability in terms of brain, kidney, and eye anomalies.