Pathogenic variants in the ZIC1 gene cause a multisystem disorder with craniofacial, neurological and skeletal findings. There is an evolving clinical picture; the main features that have been reported so far are listed below:
Craniofacial features
- Brachycephaly associated with bilateral coronal craniosynostosis.
- Coronal synostosis can also be accompanied by bony defects of the sagittal suture, and/or partial unilambdoid synostosis.
- Some individuals may have sagittal and lambdoid synostosis.
- Microcephaly in some individuals, with or without craniosynostosis.
- Strabismus and/or ptosis is present in ~50% of cases.
- Dysmorphic features in some cases including deep-set eyes, broad mouth, wide-spaced teeth.
Structural brain malformations
- Variable deficiency of the corpus callosum (agenesis or hypoplasia).
- Abnormal conformation or dilatation of the cerebral ventricles.
- Abnormalities of the posterior fossa including hypoplasia of the pons, cerebellar vermis and cerebellar hemispheres, Dandy-Walker malformation or rarely rhombencephalosynapsis.
- Spina bifida and tethered cord in some individuals.
- Optic nerve hypoplasia (one case).
Neuropsychological disorders
- Developmental delay/Learning difficulties ranging from mild to severe.
- Autistic traits in some, such as dependency on routines and limited range of interests.
- Behavioural issues including outbursts of aggressive behaviour or major mood swings have been reported.
- Limited communication in more severly affected individuals.
- Abnormalities of tone.
- Seizure disorder in some cases.
Musculoskeletal anomalies
- Progressive scoliosis.