ZIC1

Clinical Characteristics

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.