The neurological aspects related to POGZ mutation: case report and review of CNS malformations and epilepsy

Excerpt

POGZ (pogo transposable element-derived protein with zinc finger domain) gene encodes a multi-domain protein that regulates chromatin remodeling, chromosome segregation, and mitotic progression. Pathogenic POGZ mutation makes the majority of cells to exit mitosis prematurely with the formation of polyploid cells, which subsequently causes cell death or genomic instability in the subsequent division cycles. A pathogenic mutation is likely to deplete neurogenic progenitor cells with subsequent development of a decreased number of neurons and neurodevelopmental phenotype. Clinical features of pathogenic POGZ variants are autism, intellectual impairment, microcephaly, short stature, hypotonia, facial dysmorphisms, strabismus, hearing loss, and growth retardation. Diagnosis of POGZ variants is underestimated, especially in the presence of isolated autism and/or intellectual impairment. Though neurobehavioral phenotype is common and core features have been described in some details, the CNS malformations and epilepsy phenotype have not been systemically investigated. However, an expeditious syndromic diagnosis may be delayed due to a lack of awareness of these findings. Though neurologic phenotypes are variable, there is evidence of some shared MRI and epilepsy features, suggesting a distinct syndrome. …