Deletion of the KANK1 gene (also called ANKRD15), located at chromosome position 9p24.3, has been associated with neurodevelopmental disease including congenital cerebral palsy, hypotonia, quadriplegia, and intellectual disability in a four-generation family.
These data led us to conclude that small deletions involving KANK1 do not cause a highly-penetrant influence of large effect size and they are unlikely to contribute significantly to the aetiology of disease in patients with development delay, intellectual disability, autism or cerebral palsy.
Previous studies have identified mutations in the actin-capping protein KANK1 and the adaptor protein-4 complex in forms of inherited cerebral palsy, suggesting a role for components of the dynamic cytoskeleton in the genesis of the disease.
Interestingly, two mutations affecting AP4M1 and AP4E1 have recently been found to cause cerebral palsy associated with severe intellectual disability.
Mutations in COL4A1 are well described and result in brain abnormalities manifesting with severe neurological deficits including cerebral palsy, intellectual disability, and focal epilepsy.
Our investigations identified loss-of-function mutations in AP4S1/SPG52 in four children (three families) who had previously received a diagnosis of diplegic/quadriplegic CP.
The specificity increased to 100 % considering that in one case, initially classified as a non-CP lesion (xanthogranuloma), the identification of a CTNNB1S47R lead to histological re-evaluation and reclassification of the lesion as aCP.
Polymorphisms in IL-6 or IL-4 may act as susceptibility genes, in the presence of viral exposure, for the development of hemiplegic and quadriplegic CP.