Clinical Guidance

GLI3-related Greig cephalopolysyndactyly syndrome (GLI3-GCPS) is characterized by macrocephaly, widely spaced eyes associated with increased interpupillary distance, preaxial polydactyly with or without postaxial polydactyly, and cutaneous syndactyly. Less common features include hypoplasia or agenesis of the corpus callosum, developmental delay, intellectual disability, and seizures. To date, approximately 300 individuals with GLI3-GCPS have been reported with a pathogenic variant in GLI3 [Baas et al 2021 (includes individuals with isolated preaxial polydactyly), ]. Frequency of select phenotypic features associated with GLI3-GCPS is based on these reports [, , , , , , , , , , , , , , , , , , , , ]. Table 2. GLI3-Related Greig Cephalopolysyndactyly Syndrome: Frequency of Select Features

Diagnostic Criteria

No consensus clinical diagnostic criteria for GLI3-related Greig cephalopolysyndactyly syndrome (GLI3-GCPS) have been published.

Suggestive Findings

GLI3-GCPS should be suspected in individuals with the following clinical features and family history.

Clinical features

• Macrocephaly

• Widely spaced eyes associated with increased interpupillary distance (97th centile)

Management Guidelines

No clinical practice guidelines for GLI3-related Greig cephalopolysyndactyly syndrome (GLI3-GCPS) have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with GLI3-GCPS, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 7. GLI3-Related Greig Cephalopolysyndactyly Syndrome: Recommended Surveillance