NASHVILLE, Tennessee — Parent-initiated genetic testing of healthy newborns can lead to clinical diagnoses, according to data presented at the annual National Society of Genetic Counselors conference held here this week.
According to Han Chao, a senior laboratory genetic counselor at Fulgent Genetics, there is increasing interest in genetic screening of healthy newborns, but little information on the clinical utility of such testing.
In a retrospective analysis, Chao and colleagues examined the diagnostic findings of more than 470 newborn genetic analyses sought by consumers through Fulgent's testing lab. As Chao reported, the vast majority of tests came back negative, but positive findings were found in a small portion of cases. These positive findings include ones that would not have been detected through other screens.
"Consumer-initiated newborn genetic analysis can result in clinically actionable genetic diagnoses for conditions that are not routinely tested for by the state-mandated screening," Chao said during her talk.
Chao and colleagues analyzed 472 consecutive consumer-initiated newborn genetic analysis cases reported back by Fulgent. While the parents or guardians sought newborn genetic analysis, Chao noted that a physician approved testing.
The newborns underwent panel testing at 255 genes. These genes had established relationships to conditions, all of which were childhood-onset — generally with symptom onset in the first year of life — and clinically actionable. Most of the genes on the panel, 145, represented metabolic conditions, but other conditions including immunodeficiency disorders and hearing loss were also represented.
Overall, 4 percent of the newborns tested received a positive result. Chao noted that only pathogenic or likely pathogenic results were returned to the families and that only diagnostic findings consistent with a molecular diagnosis of the tested conditions were reported. Nineteen newborns had positive results, with one individual receiving two diagnoses.
These diagnostic variants were found across 11 genes related to metabolic conditions, hearing loss, and others. Six of these findings were in the G6PD gene, which encodes glucose-6-phosphate dehydrogenase, and led to a deficiency.
Of the 20 diagnoses, Chao and colleagues found that 14, or 70 percent, were not included on the Recommended Uniform Screening Panel — a list of disorders that the US Department of Health and Human Services recommends that states screen for as part of their newborn screening programs — or newborn hearing screening panels. Further, 6 of the 11 conditions they found among the newborns were not included on those panels.
In one case Chao highlighted in her talk, cord blood from a 15-day-old infant was analyzed. The analysis uncovered a heterozygous pathogenic variant in COL1A2, indicating osteogenesis imperfecta. She added that the parents took the clinical report to a children's hospital, where a physician ordered additional testing, including of the parents. Neither harbored the variants, indicating it was de novo, and further supporting that it is pathogenic. A clinical checkup found the infant had blue sclera, which Chao noted can be indicative of osteogenesis imperfecta, but also of other conditions.
Without testing, Chao said the condition was not likely to have been detected this early in life. These findings suggest that consumer-initiated newborn genetic testing can lead to clinical diagnoses, Chao said.
She noted that their analysis has a few limitations, including limited access to clinical and follow-up data. Additionally, the diagnostic yield was likely influenced by which genes and conditions were included in testing, she added.
As this was a pilot study, Chao plans to follow it up with a larger study, both of a larger population and with a larger panel or with exome sequencing. Additionally, she aims to investigate what the parental expectations were for testing and if those expectations were met, and the clinical implications of the results.