Harvey's Story

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-related Synaptopathy due to a de novo ("random") missense, single letter mutation (C became a T) on the 19th exon of one of Harvey's DLG4 alleles.  DLG4 'codes' the production and structure of the PSD-95 protein. PSD-95 is vital protein that scaffolds with several other proteins to build neuronal connections in the brain.

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 several world-renowned researchers and experts including, but not limited to: the Yu Lab, Everlum Bio, Dr. Rami Aqeilan's lab at Hebrew University at Jerusalem, Jackson Labs in Maine, University of Alabama at Birmingham's Precision Medicine Lab, and the guidance of researchers studying DLG4 in Denmark and Canada, we are exploring treatments, which include:

1) DNA Gene Therapy called an AAV, which sends a non-harmful virus into the body with a healthy copy of DLG4

2) RNA-based treatment called an ASO, which targets the mutation at the mRNA level

3) Protein-based treatment, which will examine the effects of large drug libraries on Harvey's neuronal functioning and hopefully improvement in his PSD-95 functioning or compensation of other healthy synaptic proteins

We are also working with two labs on the development of two DLG4 animal models. A Harvey specific mouse, with his genetic backbone and suspected Dominant/Negative mutation (estimated 10% of DLG4 patients have a dominant/negative mutation-meaning the mutated protein is not degraded by the body-causing additional negative impacts as well as haploinsufficiency), as well as a rat with a repeating Loss of Function/Haploinsufficient (mutated protein is degraded by the body and leaves the child with only half of the healthy protein needed for proper functioning), nonsense mutation that will allow for research for the other estimated 90% of the DLG4 community.  

We also continue to advocate with other researchers around the world who are now focusing on DLG4, including a pilot phenotype/genotype study at Children's Hospital of Philadelphia and other natural history study data collection with the Danish team.  

Once this work is completed, we plan to goto the FDA to begin the approval process as we work through our toxicology and safety studies.