Greig Cephalopolysyndactyly, Pallister-Hall syndrome, Isolated Polydactyly

Major finding of Greig Cephalopolysyndactyly include macrocephaly, ocular hypertelorism, preaxial polydactyly and cutaneous syndactyly.  Preaxial polydactyly must be present on at least one limb, but may include multiple limbs and affect hands or feet.  Postaxial polydactyly has also been reported.  Patients on the severe end of the spectrum may have seizures, hydrocephalus, and intellectual disability in addition to the above findings.

Pallister-Hall syndrome is also caused by mutations in GLI3. Pallister-Hall is characterized by multiple anomalies with a spectrum of severity reported.  the most common anomalies are polydactyly, bifid epiglottis, larynotracheal cleft and hypothalamic hamartoma.  Less common findings include renal and genitourinary abnormalities, imperforate anus, pulmonary segmentation and other skeletal anomalies.

Both of these disorders are inherited in an autosomal dominant pattern.

Mutations in GLI3 have also been associated with isolated polydactyly.

Sequencing of GLI3 will identify the underlying genetic defect in approximately 70% of cases of Greig Cephalopolysyndactyly.

Approximately 95% of patients with Pallister-Hall syndrome will have a mutation in GLI3.