SPRED1 and neurofibroma: By NGS, a SPRED1 pathogenic variant that was previously described, [12] (c.349 C>T causing a premature stop codon), was observed in a five year old child, with macrocephaly, diffuse Cal spots, freckling, no neurofibroma, no Lisch nodule neither coroideal amartoma; the father had the same clinical phenotype.