A genetic study of 31 Rwandan children with autism identified a likely genetic explanation in four children, or 12.9%. The researchers describe the result as exploratory and caution that it cannot establish a diagnostic rate for all autistic children in Rwanda.
The analysis used trio exome sequencing, meaning each child was tested alongside both biological parents. It examined 233 genes linked to autism and related neurodevelopmental conditions, as well as copy-number variants, which involve missing or duplicated sections of DNA.
What the testing found
Four children had findings classified as likely pathogenic. Three of those variants were de novo, meaning they were not detected in either parent and appeared to have arisen in the child.
The findings involved GABRB3, SYNGAP1, a deletion on chromosome 1p35.3-p35.2 and a deletion involving GNAS. The GNAS deletion was inherited from the child’s mother, who did not have the condition, making that result more difficult to interpret.
All four children with a likely pathogenic finding had severe autism, and three had syndromic autism. The source uses “syndromic autism” for autism occurring alongside a broader genetic or medical condition.
Five other children had seven variants of uncertain significance. These included variants involving SHANK3, SYNJ1, KIF15, HUWE1 and EPG5. When these findings were added to the four likely pathogenic results, 9 of 31 children—or 29.0%—had a genetic finding that matched their symptoms.
That expanded figure is an upper bound, not a diagnostic rate. A variant of uncertain significance is not a diagnosis, and the source states that such findings should not guide care decisions until more evidence is available.
Who took part
The children were aged 2 to 18 and had been diagnosed at Ndera Neuropsychiatric Teaching Hospital in Rwanda. Of 34 children initially recruited, three who tested positive for Fragile X syndrome were removed before sequencing. The remaining 31 children and their parents underwent testing.
The group had substantial developmental and clinical needs: 22 children had severe autism, eight had moderate autism and one had mild autism. Intellectual disability was present in 30 of the 31 children, while 25 had delayed speech, 17 had global developmental delay and eight had seizures.
Because the study group was largely made up of children with severe, complex autism and intellectual disability, the source says the yield would likely be lower among all autistic children in Rwanda.
Why interpretation remains difficult
Researchers say African populations are underrepresented in genetic reference databases. That lack of comparative data can make it harder to determine whether a genetic variant is harmful, harmless or still uncertain.
The five children with uncertain findings had not undergone new laboratory testing to establish the variants’ functional effects. The inherited GNAS finding also remains difficult to interpret because it came from a mother who did not have the condition.
The study was limited by its small sample, recruitment from a single referral hospital, exclusion of children with Fragile X syndrome and the scope of exome testing. No confidence interval was reported, and the exact diagnostic yield cannot be established from 31 families.
What the findings may add
A genetic diagnosis does not treat autism. According to the source, however, identifying a likely genetic explanation may provide information about why a child has particular developmental features, help doctors monitor linked problems such as seizures and inform the chance that a future child could be affected.
The findings add to a limited body of autism genetics research in African populations. The researchers conclude that more African genomic data is needed before genetic testing results can be understood with greater precision.
For context, a 2019 meta-analysis cited by the source reported yields of 36% across neurodevelopmental disorders, 16% in studies focused mainly on autism and 53% in developmental disorders accompanied by other medical problems. Trio exome studies of autism and related conditions commonly report yields of about 10% to 30%, depending on the people included.
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