What is MCOPS12?

Syndromic Microphthalmia 12 (MCOPS12) is an ultra-rare neurodevelopmental disorder caused by mutations in the retinoic acid receptor beta (RARB) gene (Srour et al., 2016). 

It was first described in the medical literature in 2013 (Srour et al. 2013)  The most recent systematic review, published in 2023, compiled clinical data from 52 individuals worldwide, making MCOPS12 one of the rarest disorders known (Caron et al 2023). Because many children with this condition may be undiagnosed or misdiagnosed as having cerebral palsy or an unspecified neurodevelopmental disorder, the true number of people living with MCOPS12 is likely higher. 

Most children with MCOPS12 show a combination of developmental eye anomalies (such as microphthalmia, meaning one or both eyes are smaller than normal), low muscle tone (hypotonia), and progressive movement disorders (dystonia and/or spasticity) that appear in the first years of life (Trieschmann et al. 2023). Some  also have a global developmental delay, swallowing difficulties, and peripheral defects such as diaphragmatic anomalies or congenital heart defects. The range of symptoms is wide and varies strongly in severity, and not every child has every feature. 

MCOPS12 is usually an autosomal dominant condition, meaning that a change in just one of the two copies of the RARB gene is enough to cause the disorder. In most families the gene change happens spontaneously in the affected child and is not present in the parents – this is called a de novo variant. In a small number of families the variant is inherited. A very rare recessive form, in which both copies of RARB are affected, has also been reported (Srour et al. 2013).