Our son has very rare genetic disorder, due to a random, single letter change in his DNA on the DLG4 gene. This mutation impacts how his body produces a protein, which is necessary for learning everything, including walking, talking, and eating. But we can change that with a novel DLG4 therapeutic, called an ASO.
In March of 2020, we gave birth to our second child, Harvey, in Seattle, Washington, just three days prior to the first COVID-19 lockdown. We felt so fortunate to head home with what appeared to be a healthy little boy. But by six months, we began to notice that Harvey was struggling to meet developmental milestones like head control, screaming during tummy time, lack of use of his right arm, ongoing concerns with eye crossing or strabismus, and he wasn’t showing any signs of learning to crawl.
By eight months, we were gravely concerned and sought guidance from our pediatrician who immediately sent us to Seattle Children's Neurology, who expedited Harvey’s case based on presenting concerns. It was December 23rd, 2020. As many families were looking forward to holiday festivities after such a stressful past year, we were about to embark on the hardest journey of our lives.
In early January 2021, just a few days prior to our move back to Austin, Texas, Harvey underwent a brain MRI and several blood panels, as Harvey’s Neurologist was concerned that Harvey was presenting with signs of a perinatal stroke. When the results game back with no concerns on his bloodwork and a fairly normal brain MRI (just delayed myelination), we felt so relieved. Maybe things weren’t going to be as devastating as we had expected. Little did we know it would be an almost year-long odyssey from first concerns to receiving a diagnosis.
As soon as we relocated back to Austin, we began seeing Neurologists at Dell Children’s, who after reviewing the brain MRI and bloodwork results, decided to order our first round of genetic testing. While we waited for results, we also were instructed to see a whole slew of specialists including Orthopedists, Ophthalmologists, Audiologists, Gastroenterologists, Geneticists, EEGS, and so on, —with one specialist literally remarking, ‘he’s a mystery'—as well as a plethora of therapy: Occupational Therapy, Physical Therapy, Speech and Feeding Therapy, Vision and Mobility Therapy, and Applied Behavioral Analysis therapy due to significant and ongoing delays in motor skills and muscle tone including repetitive behaviors such as rocking and odd hand mannerisms, speech, feeding, and socialization concerns, such as lack of appropriate eye contact, which eventually led us to a Autism Spectrum Disorder diagnosis as well.
Finally, when Harvey was nearly 18-months-old, after two rounds of genetic testing that ultimately included Whole Exome Sequencing (WES), we received Harvey's diagnosis of an ultra-rare genetic disorder, DLG4-Synaptopathy due to a de novo ("random") missense mutation on one of his DLG4 alleles. DLG4 'codes' the production and structure of the PSD-95 protein. PSD-95 is vital protein that scaffolds with several other proteins in the brain for proper synaptic brain development and appears to be structurally changed in Harvey's missense mutation.
We do not know what Harvey’s future holds, but given his type of mutation, there appears to a high likelihood of Harvey having a severe cognitive disability, development of seizures, ongoing and continued odd repetitive behaviors typical of children with an Autism Spectrum Disorder diagnosis, and possible ongoing lack of motor control. This means Harvey may never walk, or talk, or feed himself without treatment.
Immediately following Harvey’s diagnosis, we found a parent support group of about 30 other families around the world affected by DLG4 and began exploring any treatment options. It has taken months, but we have learned so much about genetic treatments available today, such as the amazing results of Spinal Muscular Atrophy (SMA) treatments, including ASOs and CRISPR for rare eye diseases. Please visit our research page and ClinicalTrials.gov to learn more about these amazing treatments. We are now embarking on a journey of developing a treatment for DLG4 and are asking for your help!
With the guidance of Perlara’s Consulting team, we are exploring treatments with Everlum Bio, a small biotech Contract Research Organization (CRO) in Austin, TX focusing on creating treatments for rare genetic disorders. At Everlum Bio we will develop Induced Pluripotent Stem Cells (iPSC) derived neurons. From there we can test a large library of up to 7,000 small molecules drugs to see if we can find improvement in the production of PSD-95 and symptoms of DLG4. In addition, we plan to develop an allele specific Antisense Oligonucleotide (ASO) at Everlum Bio under the consultation and guidance of world-renowned researcher, Tim Yu, which could target Harvey's mRNA and help alter the effects of the DLG4 mutation. We also continue to advocate with other researchers around the world who are now focusing on DLG4. In addition, we are beginning to develop a mouse model with Harvey's specific mutation and partnering with our local Children's Hospital to coordinate Harvey's medical care. Once this work is completed, we plan to goto the FDA for approval of these treatments.
We truly believe we can find a treatment path and not only find a treatment for Harvey, but a treatment for DLG4, other synaptopathies, forms of Epilepsy, and types of Autism Spectrum Disorders.
We need to do more, and we can do more with your support.
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