Variable phenotype in Greig cephalopolysyndactyly syndrome: Clinical and radiological findings in 4 independent families and 3 sporadic cases with identified GLI3 mutations

• Published in: American journal of medical genetics. Part A Vol. 120A; no. 1; pp. 49 - 58
• Main Authors: Debeer, Philippe, Peeters, H., Driess, S., De Smet, L., Freese, K., Matthijs, G., Bornholdt, D., Devriendt, K., Grzeschik, K.-H., Fryns, J.-P., Kalff-Suske, M.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-07-2003
• Subjects: Alleles; Craniofacial Abnormalities - diagnostic imaging; Craniofacial Abnormalities - genetics; DNA Mutational Analysis; DNA-Binding Proteins - genetics; Facies; Family Health; Female; Genes, Dominant; Genetic Markers; GLI3; Greig cephalopolysyndactyly; Heterozygote; Humans; In Situ Hybridization, Fluorescence; Kruppel-Like Transcription Factors; Limb Deformities, Congenital - diagnostic imaging; Limb Deformities, Congenital - genetics; Male; Mutation; Mutation, Missense; Nerve Tissue Proteins; Pedigree; Penetrance; Phenotype; Polydactyly - diagnostic imaging; Polydactyly - genetics; Polymorphism, Single-Stranded Conformational; postaxial polydactyly; preaxial polydactyly; Radiography; Syndactyly - diagnostic imaging; Syndactyly - genetics; Syndrome; Transcription Factors - genetics; variability; Zinc Finger Protein Gli3
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.20018

Greig cephalopolysyndactyly (GCPS) (OMIM 175700) is an autosomal dominant disorder characterized by a distinct combination of craniofacial, hand and foot malformations. In this report, clinical and radiological findings of 12 patients with GCPS derived from 4 independent families and 3 sporadic cases with documented GLI3 mutations are presented with particular emphasis on inter‐ and intrafamilial variability. In a particularly instructive family in which 9 members of 4 generations could be studied clinically and molecularly, a missense mutation (R625W) is transmitted and shows a partially penetrant pattern. In a branch of the family, the GCPS phenotype skips a generation via a normal female carrier without clinical signs providing evidence that GCPS does not always manifest full penetrance as generally supposed. © 2003 Wiley‐Liss, Inc.