The odds of my daughter developing her medical condition were 1 in 750 million – The Boston Globe

Do you understand? The pilots message was clear: If prone to hysteria, I should not accompany my 18-month-old daughter, Robbie, heavily sedated after seizing, on the medical evacuation helicopter headed for Boston Childrens Hospital. I nodded authoritatively. While flying, I stared at my little girl, willing her better while silently pinching deep, crescent moon indentations into my arm, my fingernails deflecting me from this crippling reality.

Robbies well-being had caused anxiety for my husband, Chris, and me long before this particular crisis shortened our Falmouth vacation. At 4 months, she was unable to bottle feed, so we petitioned the Massachusetts Early Intervention Division for an assessment. The program, which identifies developmental delays early and provides necessary services, determined Robbie was universally below the developmental curve. Yet we possessed blind optimism. Shed crush that curve, eventually.

But Robbie was not crushing it. Indifferent to external motivation, she was incapable of tolerating her therapies, ending each session with unrousable sleep episodes. At 16 months, as unmet milestones accumulated, she received a complete developmental assessment indicating global developmental delay. The burning question was, Why?

An MRI indicated that Robbie has periventricular leukomalaciabrain damage often resulting in cerebral palsy, which aligned with her symptoms. My husband and I debated the perceived physical and environmental affronts my prenatal self had suffered. Soon, her neurologist at Massachusetts General Hospital offered a lead: Robbies brain abnormalities actually pointed to a genetic origin, necessitating testing.

> Related: For more on Boston Childrens 150th anniversary, click here.

After an excruciating wait of eight weeks, the resulting report bewildered us: Robbie had become the 10th person in the world diagnosed with hereditary spastic paraplegia type 47 (SPG47), a slowly progressive neurodegenerative disorder brought on by a disease-causing strain in the AP4B1 gene. The odds of such a diagnosis? One in 750 million. The odds of being struck by lightning in a lifetime? One in 15,300. Some time later, after Id regained my sense of humor, my son asked, Whats wrong with Robbies pants? I stifled a laugh, explaining to him, genes, not jeans, are found in every person, determining our hair, eye color, even height. And Robbie has a broken one causing her problems.

Shortly after Robbies crushing diagnosis in 2016, we connected with Kevin and Angela Duffy, a couple from Philadelphia whose daughter, Molly, then 2, was also the 10th person to be diagnosed with SPG47 (no protocol existed then to fully track these cases). The four of us needed to learn more about SPG47, beginning with how to defeat it. Together, in 2016, we cofounded a nonprofit organization we called Cure SPG47 (now Cure AP-4) and pledged to identify treatment. Miraculously, incredible opportunities soon emerged.

When Robbie started preschool, I filled my days with research. In the evenings while the kids slept, my husband and I scoured medical publications, contacting authors to whittle down which therapies held promise and securing our nonprofits scientific advisers. Eventually, we determined that gene therapy research through neuroscientist Mimoun Azzouz at Englands University of Sheffield would be the optimal route toward impeding SPG47s relentless progression.

Our quest also led us to child neurologist Darius Ebrahimi-Fakhari at Boston Childrens, who proposed targeted drug screening that could lead to repurposing FDA-approved drugs for treatment. We learned the AP4B1 gene works in tandem with three other AP-4-associated hereditary spastic paraplegia genes. (A simplified explanation from a molecular biologist: Consider each AP-4 gene a tire on a car. No matter which AP-4 tire pops, the resultpresenting symptomsis the same.) Ebrahimi-Fakhari soon established an international AP4-HSP-registry and natural history study, identifying patients worldwide. Distraught parents, in varying languages, began seeking us out for advice and support.

My hunger to learn more is insatiable; the response, staggering. Researchers from prestigious institutions are generously dedicating their time and resources. Importantly, excitingly, very early stage drug screening and gene therapy research show promise. And weve learned that any approach that helps correct protein transport in SPG47 could offer new insights into much more common neurodegenerative diseases, including Alzheimers. Finding answers to this genetic mystery could go way beyond helping just Robbie and Molly.

Robbie turned 5 this year surrounded by friends; we had a dance party featuring her favorite Imagine Dragons songs. Shes alert, inquisitive, and idolizes her big brother, as he does her. Robbies social aptitude and clever humor inch her closer to the curve. Our optimism is warranted.

These reverberations of one solemn vow shared between two sets of desperate parents seems like a dream Id awaken from, were I to pinch myself. But I would never do that. I savor todays reality.

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The odds of my daughter developing her medical condition were 1 in 750 million - The Boston Globe