Current Diagnoses: Coloboma and Microphthalmia - left eye, Anopthalmia – right eye, Blind, Reflux, Developmental delay, Cerebral Palsy (Dystonia, Choreoathetosis, Spasticity), Chiari 1 malformation - borderline, RARB genetic mutation in Chromosome 3 (MCOPS12), Reactive Airways dysfunction syndrome, Dysarthria, Severe obstructive apnea

 

Sophia was born with Microphthalmia and Coloboma in her left eye and Anopthalmia in the right.  She had functional vision in her left eye until 9.5 years old when the retina detached (combined tractional / rhegmatogenous detachment) and surgeries were unable to repair it. Diagnosed with CP at age 1.5 years with the most severe presentation in her lower extremities, upper extremities were moderately affected.  Able to weight bear continuously, but gait progress has been difficult and must use a supported walker. Sophia requires a wheelchair for distances over 25 feet.  She can self-feed with finger foods but is unable to use a spoon independently and needs assistance at times with a fork or lidded cup.  She can hold a writing implement, but is unable to make intelligible marks.  Multiple GI conditions at birth which have mostly resolved with diet and careful control of bowel movements via natural substances.  Language delay until age 6 and is now at a sixth grade level in expressive and receptive language skills.  

 

After an exome sequence in 2015 (age 7), we discovered that Sophia had a retinoic acid receptor beta (RARB) gene alteration in Chromosone 3, located in exon 8.  Formally seen as c.1159C>T (p.R387C) in which Cytosine was replaced by Thymidine in nucleotide 1159 causing Arginine (R ) at amino acid position 387 to be replaced by a Cysteine.  Due to the amino acid alteration, there is a 2 to 3 fold increase in RARB transcriptional activity which suggests a gain of function.  

 

MCOPS 12 (Microphthalmia syndromic 12) is the new syndrome name for all RARB gene mutations

 

MCOPS12 is an ultra-rare neurological disease caused by a mutation in the retinoic acid receptor beta (RARB) gene. Common phenotypes are microphthalmia, severe movement and speech disorders and intellectual disability. 

 

If you know an individual who has this mutation, please join this website at: https://www.acureforsophiaandfriends.com/ and if you are willing to share your story (Name, Year of birth, Parents, Home town/country, and "message from the parents”) along with a picture, it would be a wonderful step towards building our community throughout the world. The more people we have registered in one place, the more possibilities we have to work towards therapeutic treatments. I am so grateful to the Pell family for helping to move this research forward and allowing us to come together in one forum. The Pells have also registered a non-profit association in Austria to start fundraising campaigns (beginning within Novartis) and to give further therapeutic development activities a legal body.

 

UPDATED ON 6-6-2021