Family history revealed a sister aged 22 years with cerebral palsy and a healthy 15-year-old brother, who were both severely pigmented with high ACTH levels.
Given the very poor prognosis of infantile spasms especially in such conditions as cerebral palsy, the combination of ACTH and vigabatrin appears to be an interesting therapy advance with very few side effects.
Developmental motor deficits induced by combined fetal exposure to lipopolysaccharide and early neonatal hypoxia/ischemia: a novel animal model for cerebral palsy in very premature infants.
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.
After evaluation of our case series and reconsideration of the literature, we propose that KANK1 aberrations do not frequently cause CP but cannot exclude that they represent a risk factor for ASD, especially when the coding region of the shorter, alternate KANK1 transcript (termed "transcript 4" in the UCSC Genome Browser) is impacted.
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.
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.
In 23 patients molecular diagnosis was reached and included 5 hereditary spastic paraplegia genes (SPG) in spastic CP mimics; HPRT1, TH, QDPR, DDC in dystonic CP mimics; ADCY5 and NIKX2-1 in choreic CP mimics; CANA1A in ataxic CP mimics; and SPG, PDHA1, NIKX2-1, AT, SLC2A1 and SPR in mixed CP mimics.
In 23 patients molecular diagnosis was reached and included 5 hereditary spastic paraplegia genes (SPG) in spastic CP mimics; HPRT1, TH, QDPR, DDC in dystonic CP mimics; ADCY5 and NIKX2-1 in choreic CP mimics; CANA1A in ataxic CP mimics; and SPG, PDHA1, NIKX2-1, AT, SLC2A1 and SPR in mixed CP mimics.
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.