Novel compound heterozygous pathogenic variants in the lama1 gene associated with Poretti-Boltshauser Syndrome

Poretti-Boltshauser syndrome (PTBHS) is an autosomal recessive disorder, whose manifestations include hypoplasia of the cerebellar vermis, intellectual disability with oculomotor apraxia, dysplasia, and cerebellar cysts. The phenotype originates from pathogenic variants in the LAMA1 gene, responsible for encoding the Laminin alpha-1 protein. Objective: to describe and report to the world literature the clinical case of a young infant with PTBHS. Clinical case: a case of a minor infant is reported, who presented apneas, respiratory symptoms and distinctive physical characteristics. Imaging studies revealed brain abnormalities, such as agenesis of the corpus callosum and ventriculomegaly. Complete genomic sequencing was performed, identifying two mutations in the LAMA1 gene (p.Arg2128Trp and p.Pro839Ser), which have not been described in the literature, nor reported in population databases such as Clinvar or gnomAD. Bioinformatic analysis suggested that these variants were pathogenic and associated with the observed clinical symptoms, such as hypoplasia of the cerebellar vermis, intellectual disability, and cerebellar abnormalities. Conclusion: The first documented phenotype/genotype correlation in an infant with PTBHS is represented. The importance of genomic studies that include bioinformatics and the reclassification of the significance of the genetic variants found in molecular studies is highlighted, considering the clinical and other paraclinical diagnostic aids that allow establishing a timely diagnosis and adequate treatment based on 4P medicine (personalized, predictive, preventive and participatory).