Within weeks following Tiana’s normal birth in May 2013, it was clear that she would not be as easy to care for as her sister, Aliyah, who is two years older.
The toughest part was her incessant crying. Jeannette Vega and her husband, Victor, a communications technology engineer, tried everything: white noise machines, co-sleeping, colic remedies, swaddling, a vibration device. Nothing worked. Tiana rarely slept more than two hours at a stretch.
Jeannette relied on weekly emails from a popular website that ticked off developmental milestones and noticed that Tiana was slow to reach them.
“Tiana was rarely on schedule,” the Madison, Ala., mother recalled. “Or she would hit them and then lose them.” The toddler spoke late and only a few simple words such as “Mama” and “bye.” Then she inexplicably stopped talking.
Jeannette, now 37, said she didn’t worry about the regressions. “I assumed if she did it once, she would do it again,” she said.
The Vegas say their pediatrician in nearby Huntsville didn’t seem alarmed.
But after Tiana proved to be months late learning to sit without assistance, Jeannette took a friend’s advice and enrolled the 13-month-old in Alabama’s early intervention program. The in-home program provides speech, occupational and physical therapy for developmentally delayed and disabled children.
Tiana improved — but very slowly. Sometime after she turned 2 she began to walk, an accomplishment her parents celebrated.
“It made us feel like everything is going to be OK and that she was catching up,” her mother said.
Tiana had no diagnosis and Bebin suspected that as many as 15 disparate conditions, including epilepsy or autism, might be the cause. Brain scans, genetic screens and chromosomal analysis failed to pinpoint what was wrong.
But Bebin was an integral part of a newly launched collaboration between the University of Alabama and the HudsonAlpha Institute for Biotechnology in Huntsville, a nonprofit that conducts genetic research. The goal of the project, known as CSER (short for Clinical Sequencing Evidence-Generating Research) was to determine whether whole genome sequencing could identify disorders in children with neurological difficulties who had no diagnosis.
Blood samples from both parents and the affected child can yield information about genetic variations that are not inherited.
The Vegas enrolled, then waited for the results.
During the nearly six-month hiatus, the couple decided to take their daughter to a psychologist for evaluation.
Victor said he suspected by then that his daughter might be autistic. He had relatives with autism, and Tiana had recently developed repetitive and purposeless hand movements similar to those he had seen in some people with the disorder. He and Jeannette began talking to parents of autistic children in an attempt to prepare themselves.
They also decided to move back to Orlando, where their families live.
In early December 2015, the day before their move to Florida, the couple met with the HudsonAlpha team to get Tiana’s results. Only a day earlier, the psychologist had told the Vegas she believed Tiana had autism.
But the team’s news was deeply shocking — and far worse than either expected.
Greg Cooper, a Stanford-trained geneticist and HudsonAlpha scientist who headed its CSER effort, explained to the Vegas that genetic sequencing had revealed a mutation in the MECP2 gene, which is necessary for brain function. The mutation is associated with Rett Syndrome, a degenerative and incurable neurodevelopmental disorder that almost exclusively affects girls.
First described in 1966 by Austrian physician Andreas Rett, the gene associated with Rett, which impairs brain development, was identified in 1999. The x-linked mutation, which occurs randomly, is estimated to affect roughly 1 in 10,000 girls in the United States. (Affected boys are rare and seldom survive infancy.) The syndrome is characterized by regressions in speech and motor coordination, often during the first 18 months of life. Cognitive functioning can be hard to assess because of the inability to speak or gesture. Many girls with Rett develop stereotypical “handwashing” movements.
Although Rett can be diagnosed based on symptoms, Cooper said that a genetic test offers “closure and certainty.” Because it is caused by a spontaneous mutation, scientists believe that the chance of an affected family’s future children having Rett is extremely small.
Girls with Rett appear to have a reduced life span, although they may live into their 40s and beyond. Treatment is largely supportive and focuses on managing problems such as difficulty eating, the loss of muscle control and the inability to speak.
For Jeannette, the news seemed to foretell a future that sounded inexpressibly bleak. “I spent the first 24 to 48 hours vomiting and crying,” she recalled.
The diagnosis was equally leveling for Victor. At first, he said, his frequent business trips were “a good distraction. But then I started losing it in hotel rooms.” He remembers nights spent lying on the floor weeping inconsolably and feeling utterly unable to protect his family.
But in time, having a definitive diagnosis and connecting to resources including pediatric neurologist Alan Percy, one of the world’s preeminent Rett experts at the University of Alabama-Birmingham, helped the couple move forward.
“I give the family a lot of credit. They were really proactive and are extremely resilient. And they’ve tapped into what’s going on in terms of research,” Bebin said.
“The genetics counselor getting us connected to other families who have Rett — it was life-changing,” Jeannette said.
After 18 months in Orlando, the Vegas moved back to Madison, in part because of the proximity to care for Tiana and the support of other families.
In the last few years, life seems to have stabilized, Jeannette said.
Tiana is attending a local elementary school with a full-time aide. Because of her significant difficulty eating, she now has a feeding tube that has enabled her to gain weight, and improved her strength and energy. She sleeps through the night and uses an eye gaze communication device. She seems happy, her mother says, and loves roller coasters and riding her adaptive tricycle.
Although grateful for a diagnosis, Jeannette says she does not wish Tiana had been diagnosed earlier.