The Greig cephalopolysyndactyly syndrome

Area of Science:

• Genetics
• Medical Genetics
• Developmental Biology

Background:

• Greig cephalopolysyndactyly syndrome (GCPS) is a rare, pleiotropic congenital anomaly with variable incidence.
• Key features include hypertelorism, macrocephaly, and polysyndactyly, with CNS anomalies and cognitive impairment as less frequent findings.
• GCPS is caused by loss-of-function mutations in the GLI3 transcription factor gene, inherited in an autosomal dominant pattern.

Purpose of the Study:

• To address the diagnostic challenges posed by the non-specific clinical findings in GCPS.
• To propose and validate a combined clinical-molecular definition for improved GCPS diagnosis.
• To outline diagnostic criteria and differential diagnoses for GCPS.

Main Methods:

• Clinical assessment of characteristic features: hypertelorism, macrocephaly, and polysyndactyly.
• Molecular genetic testing for GLI3 mutations.
• Analysis of family pedigrees for autosomal dominant inheritance patterns.
• Review of differential diagnoses including similar genetic syndromes.

Main Results:

• A presumptive diagnosis can be made with the classic triad of preaxial polydactyly, hypertelorism, and macrocephaly.
• Definitive diagnosis is achieved with a consistent phenotype and a confirmed GLI3 mutation or familial linkage.
• Antenatal molecular diagnosis is feasible and straightforward.

Conclusions:

• A combined clinical-molecular approach enhances the accuracy of GCPS diagnosis.
• Symptomatic treatment, including surgical interventions for limb malformations, is indicated.
• Prognosis is generally excellent, though developmental delay or cognitive impairment may occur in some cases.