In a child with agenesis of the corpus callosum and severe retardation, both cardinal features of acrocallosal syndrome (ACLS; 200990) and rare in Greig cephalopolysyndactyly syndrome (GCPS; 175700), Elson et al. (2002) identified a heterozygous 2800G-C transversion in exon 15 of the GLI3 gene, resulting in an ala934-to-pro (A934P) mutation. At birth, he had bilateral cleft lip and palate, a large anterior fontanel extending down his forehead, overriding coronal sutures, and small ears with uplifted lobes. Pronounced hypertelorism was present and cranial MRI showed agenesis of the corpus callosum. His hands showed bilateral postaxial nubbins, a broad thumb on the right hand, and a partially duplicated left thumb. There was also partial cutaneous syndactyly bilaterally. The feet displayed bilateral duplication of the big toe and syndactyly of the other toes. At the chronologic age of 56 months he was estimated to have a mental age of 21 months. We have classified the phenotype in this patient as GCPS based on the identification of a heterozygous mutation in GLI3 as opposed to homozygous mutations in KIF7 (611254), which have been identified in patients with ACLS. Biesecker (2008) stated that patients with a phenotype consistent with GCPS and a GLI3 mutation may be diagnosed definitively as GCPS.
