Management
Management by a multidisciplinary team with composition depending on patient features.
The long-term follow-up of patients should be coordinated by a Paediatrician with input from a Paediatric neurologist as required. If there is craniosynostosis, management of this will be led by a Craniofacial surgeon working closely with a multi-disciplinary Craniofacial team including input from Ophthalmology, Speech and Language therapy, Psychology, with Clincal Genetics advice as appropriate.
Special attention should be given to:
- Detection and management of coronal craniosynostosis including monitoring for raised intracranial pressure.
- Monitoring developmental progress, with attention to social/communication issues.
- Monitoring for progressive spine deformities.
- Monitoring for strabismus.
- Regular neurological evaluation.
Genetic counselling
Inheritance of ZIC1 mutations shows an autosomal dominant pattern.
The majority of reported pathogenic variants have occurred de novo and are associated with a severe phenotype. Although in general recurrence risks associated with de novo cases are low, caution should be exercised when counseling for the recurrence risk to subsequent pregnancies for ZIC1 mutation. We do not yet know how prevalent ZIC1 mosaicism will be (currently 2 mosaic variants out of 8) , but likely gonadal mosaicism in one of the unaffected parents of two siblings carrying a ZIC1 mutation has been reported and in this situation the recurrence risk is up to 50%.
A pathogenic missense ZIC1 variant has been described in a 3-generation family segregating milder features of the condition. A patient carrying a pathogenic variant in ZIC1 has a 50% risk (1 in 2 chance) of passing on this variant to his/her offspring.
Prenatal diagnosis is possible if requested by the parents.