Pierson syndrome is an autosomal recessive disorder comprising congenital
nephrotic syndrome with
diffuse mesangial sclerosis and distinct
eye abnormalities with microcoria reported as the most prominent clinical feature. LAMB2 mutations leading to lack of
laminin beta2 were identified as the molecular cause underlying
Pierson syndrome. Although LAMB2 is known to be expressed in the neuromuscular system, and defects of the neuromuscular junctions had been found in
laminin beta2-deficient mice, no consistent neurological phenotype has been described clinically in murine or human
laminin beta2-deficiency before. This is likely due to the early lethality from
renal failure. Here we provide a detailed description of
neurological manifestations and development in four patients affected by
Pierson syndrome, who survived until the age of 1.3-4.8 years owing to
renal replacement therapy. Severe
muscular hypotonia, psychomotor retardation, and
blindness were present in three patients harboring truncating mutations on both LAMB2 alleles. These symptoms were not attributable to complications of
chronic renal failure, thus representing a primary feature of the
genetic disorder. Alterations in skeletal muscle tissue from one case were compatible with a chronic denervating process. One affected girl, however, exhibited a milder course of renal disease, normal development, and preserved vision, presumably owing to some residual LAMB2 function. Our findings indicate that severe neurodevelopmental deficits have to be considered as part of
Pierson syndrome, at least in the presence of biallelic functional null mutations (complete lack of
laminin beta2). This is an important issue in the counseling of parents of an affected newborn or infant.