Research progress on pathogenic gene and molecular mechanism of congenital cranial dysinnervation disorders

Congenital cranial dysinnervation disorders (CCDDs) refer to a collection of congenital ocular motility disorders resulting from defects or abnormalities in the development of specific cranial nerves/nuclei with axonal guidance that cause primary or secondary dysinnervation.CCDDs may be familial or sporadic.Currently, multiple genes have been identified as pathogenic.For example, variants of KIF21A, TUBB3, TUBB2B and PHOX2A may cause congenital fibrosis of extraocular muscle, variants of CHN1, MAFB, SALL4 and HOXA1 may cause Duane retraction syndrome, and variants of ROBO3 may cause horizontal gaze palsy with progressive scoliosis.Based on the reported subcellular locations and functional classifications of these coded proteins, pathogenic genes have been grouped into three categories: promoting microtubule growth and assembly ( KIF21A, TUBB3, TUBB2B), regulating gene transcription ( PHOX2A/ ARIX, MAFB, SALL4, HOXA1, HOXB1), and affecting signal transduction ( CHN1, ROBO3).This article reviews recent insights into the genetics and molecular mechanisms of CCDDs.

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