Olivia’s Story

In the early morning hours of January 23, 2009, we experienced one of the greatest joys of our lives as we welcomed Olivia and her twin sister Ava into our world. We were both excited and nervous, as any first-time parents would be. Being parents to our twin girls has turned out to be the most positive, profound and deeply wonderful experiences of our lives.

When the girls were about six months old, we noticed that they were not reaching some of their developmental milestones. We contacted our State’s Early Childhood Intervention Program and we were able to get Olivia and Ava the rehabilitative programs that they respectively needed.

Developmentally, Olivia always seemed to lag behind Ava. Olivia rolled over, sat up and walked first, however, when it came to talking, Ava learned to speak, formalize sentences and possessed expressive language skills effortlessly. Olivia continued to struggle and was easily frustrated. At first, we believed that speech was the issue at hand. Both girls continued to receive Early Intervention services for prematurity and, upon aging out, then went on to receive out-patient OT, PT and speech therapies.

Around the age of 4, Ava was discharged from out-patient therapies since she had met milestones while Olivia was still struggling.

Our journey with Phelan-McDermid Syndrome began in May 2016 with Olivia’s initial diagnosis. Olivia’s diagnosis was identified through a diagnostic test called Whole Exome Sequencing Analysis.

Earlier in 2016, Olivia was under the care of Dr. Adang, a neurologist at Children’s Hospital of Philadelphia. Dr. Adang recommended further genetic testing due to Olivia’s medical history of ADHD, hypotonia, intellectual disability, developmental delays and behaviors. Olivia had been tested by a preliminary genetic test known as the microarray, which revealed a chromosomal SNP array. There were no clinically established diagnoses known to be related to those two identified imbalances. Dr. Adang then recommended Whole Exome testing. 

Exome sequencing allows for the identification of changes in an individual’s exome genetic material that are causative or related to the patient’s phenotype. It is the most comprehensive genetic test that is clinically available. Exome testing revealed that Olivia’s has a heterozygous pathogenic variant in exon 21 of the Shank3 gene. The Shank3 gene is located within chromosomal region 22q13.3. Individuals with deletions of this entire 22q13.3 region (inclusive of the Shank3 genes plus many other genes) is associated with Phelan-McDermid Syndrome.

Phelan-McDermid Syndrome is characterized by moderate to profound intellectual disability, a variety of neurobehavioral issues, seizures, and a spectrum of variable structural differences including brain, cardiac, and renal anomalies (Phelan & Rogers, 2011). There is a wide spectrum of clinical presentations with Phelan-McDermid syndrome. The pathogenic variant identified is the likely underlying genetic etiology for Olivia’s ADHD, hypotonia, intellectual disability, developmental delays and behaviors.

There was a relief in finally receiving the Phelan-McDermid diagnosis. When we researched Phelan-McDermid Syndrome, we came to understand this is a rare disease with only 1600 confirmed cases at the time. We did not know any other families afflicted and our medical team was not very familiar with Phelan-McDermid Syndrome. Most doctors do not even know what Phelan-McDermid Syndrome is.

In 2016, the Phelan-McDermid conference was held in Orlando, Florida, which we were able to attend for the first time. At the conference, we met other Phelan-McDermid families which has provided our family with support and education. We joined the rare disease registry. More importantly, we met and heard Dr. Alex Kolevzon speak at the conference. We were excited to discover that at Mount Sinai, Seaver Autism Center, Olivia would be able to participate in the longitudinal assessments and Natural History Study of Phelan-McDermid Syndrome. Our family was able to meet with the Mount Sinai staff and Dr. Kolevzon in September 2016. The testing performed has been invaluable to our family. Collaborating with the Mount Sinai experts on Phelan-McDermid Syndrome has made a meaningful and positive difference in Olivia’s life.

At times, Phelan-McDermid Syndrome has been a long and difficult struggle that has challenged our family in many ways. As we stated, Olivia is a fraternal twin whose sister, Ava, is neurotypical. The Seaver Autism Center has been instrumental in aiding our family understand Phelan-McDermid Syndrome. Dr. Danielle Halpern has even participated in Olivia’s educational IEP meetings.

Ava has been by her sister’s side at Mount Sinai for support and understanding. The Seaver Autism staff, especially Allison Durkin, make it so much fun that the girls want to go in to the Seaver Center for office visits.

Olivia’s progress at age 9 has been astounding. Every day we are amazed with her growth and look forward to what tomorrow will bring. She participates in typical swim class, numerous special needs sports such as flag football, soccer and t-ball, and in a social skills class.

We consider ourselves fortunate to be able to participate in the study at the Seaver Autism Center for Research and Treatment at the Icahn School of Medicine at Mount Sinai. Our experience with Dr. Kolevzon and the entire staff at the Seaver Autism Center and Mount Sinai was superb. The staff and doctors are all exemplary, but just as importantly, they are exceptionally understanding of our journey from birth. They are dedicated, compassionate and extremely knowledgeable. We are so grateful to have had the opportunity to participate in this research study and to be working with the Seaver Autism Center. We will forever be appreciative.

- Andrea & Bob Papageorgiou