Variable phenotype of Pierson syndrome

Pierson syndrome is caused by mutations in the LAMB2 gene, which encodes the laminin β2 chain, and is clinically characterized by congenital nephrotic syndrome (CNS) and bilateral microcoria. Here, we describe two cases of Pierson syndrome involving atypical phenotypes. Patient 1 presented with congenital microcoria and infantile nephrotic syndrome. Despite persistent nephrotic syndrome, her renal function was maintained normally until she was 6 years old. Genetic analysis revealed two frame-shifting deletions (truncating mutations) in the LAMB2 gene. Patient 2 presented with isolated CNS without ocular involvement. Her renal function deteriorated progressively over several months, and retinal detachment in the right eye developed when she was aged 10 months. LAMB2 analysis revealed a missense mutation in one allele and a frame-shifting deletion in the other allele. Electron microscopy of a renal biopsy revealed irregular lamellation of the glomerular basement membrane (GBM) in both patients. The phenotypes of Pierson syndrome vary widely, and the severity of the renal phenotype is not always parallel to that of the ocular phenotype. The phenotypic variability likely reflects genotype–phenotype correlations, but unknown genetic or environmental modifiers may play an additional role. Ultrastructural changes of the GBM are a useful diagnostic indicator.