| Popis: |
We summarize the novel association of trigonocephaly and polysyndactyly in 3 unrelated patients due to mutations within the GLI3 gene. GLI3 acts as a downstream mediator of the Sonic hedgehog signal-transduction pathway which is essential for early development; playing a role in cell growth, specialization, and patterning of structures such as the brain and limbs. GLI3 mutations have been identified in patients with Pallister Hall, Greig cephalopolysyndactyly (GCPS), postaxial polydactyly typeA1, preaxial polydactyly type IV, and in 1 patient with acrocallosal syndrome (ACLS). Until recently, trigonocephaly has not been associated with abnormalities of GLI3 and craniosynostosis is not a common feature of GCPS. However, there have been 2 prior reports of patients presenting with trigonocephaly, polysyndactyly, and agenesis of the corpus callosum, one of whom had a father with polysyndactyly. Both were originally considered GCPS, with the simplex case later considered ACLS. In retrospect, these 2 patients, with clinical diagnoses, and the 3 patients recently reported, with confirmed mutations, likely demonstrate a rare presentation of GCPS and highlight the extensive variability observed among patients with GLI3 mutations. |
