Madelaine and Ally's Story
/
RG’s Patient Research Services (RGPRS) is an initiative of Rare Genomics Institute (RG) that aims to connect rare disease patients to resources, networks, and sequencing projects, in order to help find hope for a cure. The research services team is an ongoing program offered to all rare disease patients. To contact us, click here: https://www.raregenomics.org/contact-us
Madelaine completed our Patient Application Form (https://www.raregenomics.org/rg-patient-application-form) and from there, Ally’s genome was sequenced through the iHope program. Her genome sequencing results were analyzed by RGPRS and a list of possible variants, including the Histone-4 C5 variant, was generated. Madelaine graciously shared Ally and her’s story with us through a virtual call with the hope to inspire hope and share with others the rare disease diagnostic odyssey.
Madelaine had a normal pregnancy and gave birth to a healthy baby named Ally in a small, less than 10,000 person town named Dauphin, Manitoba, Canada. Ally was Madelaine’s second daughter, with her first being her neurotypical eldest daughter, Bethany.
Things appeared normal at first. However, within a few months of giving birth, Madelaine started to notice that Ally was not turning her head to sounds, tracking objects with her eyes, or rolling over. It was clear that Ally was not like her sister, and at 8 months, Madelaine decided that Ally needed to be assessed by a doctor. The doctor told Madelaine that Ally was not reaching developmental milestones and had a small head circumference. Despite the physical exam findings and developmental delay, Madelaine and the doctors faced a challenge of diagnosing Ally without a clearer picture of what her vague symptoms meant at such a young age and how they might evolve as Ally grew older. At 12 months, Ally was still unable to walk.
Without a diagnosis, Madelaine knew that Ally’s symptoms implied something serious. Doctors continued to apply vague labels to Ally’s collection of symptoms, including “cognitive delay”, “motor delay”, and “speech delay.” Madelaine and her husband felt more alone than ever in their small town. They knew of no other family that had a child like Ally. They struggled to find a babysitter who could care for Ally’s exceptional needs, and even as parents, they struggled with getting Ally to cooperate or settle down.
As Ally began to cruise, Madelaine noticed that she would wobble and frequently fall. Besides being clumsy, Ally got frequent ear infections. Still without a diagnosis, Ally was treated with T-tubes, adenoidectomy, and tonsilectomy at 3 years old. The tubes improved her ear infections and her walking, but did not provide any clarity on Ally’s underlying diagnosis.
All this time, Ally was nonverbal, but had learned how to sign the word “more” at the age of 2. Being unable to communicate with her own child was difficult for Madelaine, and she was never able to understand her daughter’s frustrations, fussiness, or needs.
After being on the waitlist to see a developmental pediatrician for 1 year, Madelaine was finally able to bring Ally for an evaluation that could provide her with some more answers. At the appointment, autism was ruled out, and Ally was diagnosed with global developmental delay, ADHD, and hypotonia. The hypotonia explained Ally’s failure to reach her physical milestones, and collectively, the diagnoses connected the family with Canada’s Children's Disability Services. This was life-changing for Ally and her family.
Children’s Disability Services helped Ally get early interventions, including speech therapy with a non-verbal specialist, physiotherapy, occupational therapy, neurotherapy, and more. Inclusion Support revolutionized Ally’s educational experience and academic goals. Ally was also able to get an MRI which showed delayed myelination in her cerebral lobes that provided a possible explanation of her delayed cognitive development. Ally continued to receive tests through Winnipeg Children’s Hospital, which resulted in several negative diagnoses.
Madelaine was interested in getting Ally’s genome sequenced, but was unable to afford the staggering $10,000-$20,000 cost of sequencing. When Ally was 5-years-old, Madelaine found Rare Genomics’ (RG) application form online. She completed the form and did not expect Ally to be chosen. However, Ally was selected and her whole genome was sequenced.
The Rare Genomics’ Patient Advocacy Team (PAT) connected with the family after sequencing was completed and referred them to the RGPRS team to begin reanalysis of Ally’s genome sequencing results. The data was uploaded to the Emedgene and Patient’s Know Best (PKB) platforms, which provided the RGPRS team with genetic variants that might explain Ally’s constellation of symptoms, which included: failure to thrive in infancy, generalized hypotonia, severe global developmental delay, cavernous hemangioma, abnormal facial shape, limb tremor, among others. Each of the possible variants were critically evaluated by a RGPRS team member and corroborated by research papers that reported children who displayed similar symptoms to Ally’s. After an extensive search, the RGPRS team concluded that Ally had a histone 4 C5 (H4C5) variant. They connected Madeleine to Dr. Gijs van Haaften, a researcher in the Netherland’s, who was collecting a cohort of patients that also had histone 4 variants. The RGPRS team hoped “this connection [would] help the family finally end their diagnostic journey, learn more about Allyson's condition, and find a community of families like their own.”
With an answer, Madelaine found peace. Dr. Gijs van Haaften confirmed that Ally’s phenotype fits missense variants in the H4 genes. Although Ally’s mutation had not been seen in any other patients, Madelaine was motivated to get in touch with families with children with H4 mutations. She started her search for novel therapies or interventions that may benefit Ally.
Today, Madelaine continues to communicate with Ally’s geneticist Dr. Patrick Frosk and is interested in enrolling Ally in future H4 cohorts in order to contribute to research investigating H4-related diseases. While she maintains her hope for a cure, she is aware that there will likely never be one. However, Madeline is determined to do whatever it takes to optimize Ally’s current state and set her up for success in her adult life. Madelaine says, “My dream is for my daughter to live independently, safely, and happily.”