Greig cephalopolysyndactyly syndrome and 7p14 deletion

Greig cephalopolysyndactyly syndrome (GCPS) and chromosome 7p14 deletion facial dysmorphism and developmental delay.

Greig cephalopolysyndactyly syndrome (GCPS) is an autosomal dominant disorder. The main manifestations of this condition are macrocephaly, facial dysmorphism and polysyndactyly (preaxial polydactyly is an association with syndactyly between several fingers and/or toes). Usually the genetic basis of this condition is a mutation in the GLI3 gene, located at 7p14.1. There are also several dozen reports on patients with GCPS who had translocations disrupting the GLI3 gene or deletions of this area of 7p leading to a complete absence of this gene. Usually the patients with GCPS caused by mutations are intellectually normal, whereas most patients with deletions show developmental delay. The authors report on a boy (who was followed for 3 years) diagnosed with GCPS right after birth. He had macrocephaly, multiple dysmorphic features (sparse eyebrows, a broad nasal base, broad columella, pit of the crus of the helix) and abnormalities of extremities: preaxial polydactyly [additional thumbs were surgically removed], broad thumbs and complete syndactyly I-III toes. MRI of his brain showed hypoplastic corpus callosum and acqueductal stenosis. The child showed significant developmental delay. A cytogenetic examination revealed an 18.37 Mb deletion in the 7p14.2p11.2 area. As a result he lost not only the GLI3 gene, but also ~200 other genes, including 23 “morbid” genes (genes known to cause genetic disorders). At least 3 of these genes (CDK13, CAMK2B and RALA) may cause neurodevelopmental problems. The authors suggest that loss of these genes may contribute to developmental delay in this boy. The authors also analyzed possible effects of other genes lost in the patient.

Kozma K. et al. “Greig cephalopolysyndactyly contiguous gene syndrome: case report
and literature review”. “Genes” (Basel) 2021, v. 12:1674.

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