Background Cerebral palsy is a heterogeneous group of neurodevelopmental brain disorders resulting in motor and posture impairments often associated with cognitive, sensorial, and behavioural disturbances. Hypoxic–ischaemic injury, long considered the most frequent causative factor, accounts for fewer than 10% of cases, whereas a growing body of evidence suggests that diverse genetic abnormalities likely play a major role.
Methods and results This report describes an autosomal recessive form of spastic tetraplegic cerebral palsy with profound intellectual disability, microcephaly, epilepsy and white matter loss in a consanguineous family resulting from a homozygous deletion involving AP4E1, one of the four subunits of the adaptor protein complex-4 (AP-4), identified by chromosomal microarray analysis.
Conclusion These findings, along with previous reports of human and mouse mutations in other members of the complex, indicate that disruption of any one of the four subunits of AP-4 causes dysfunction of the entire complex, leading to a distinct ‘AP-4 deficiency syndrome’.
- Cerebral palsy
- mental retardation
- gene deletion
- clinical genetics
- epilepsy and seizures
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Funding This work was funded in part by grant MH074090 (to DHL and CLM) from the National Institutes of Health.
Competing interests None declared.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the Emory University Institutional Review Board.
Provenance and peer review Not commissioned; externally peer reviewed.