Microphthalmia, syndromic 12 (MCOPS12) is an ultra-rare and complex neurological disease. The most common symptoms are microphthalmia, severe (progressive) movement disorders and variable cognitive impairment. Movement disorders may include spasticity and dystonia. In addition, malformations such as defects of the cerebellum (Chiari type I malformation) and holes in the diaphragm (diaphragmatic hernia) have been observed [Srour et al., 2016].
MCOPS12 is a form of syndromic microphthalmia and is caused by a point mutation in the retinoic acid receptor beta (RARB) gene. Several variants of the point mutation have been identified, with mutation c.1159C>T (p.R387C) being the most prominent (i.e. cytosine is replaced by thymine in nucleotide 1159 causing arginine (R) at amino acid position 387 to be replaced by cysteine (C) in RAR-beta). Depending on the point mutation variant, the disorder can be variable with some individuals having milder manifestations or displaying only a subset of them. RARB gene mutations usually occur spontaneously and are non-inherited genetic changes (de novo mutations) but can be inherited in some families in an autosomal dominant manner.