According to an international consortium led by researchers at Baylor college of Medicine (BCM), there is a chromosomal deletion linked with changes in white matter in the brain. This is associated with delayed language development in children from Southeast Asia or with ancestral connections to this region. They point out that many of these children who are essentially late-talkers have the capacity to overcome their speech and language issues as they grow.
This was a collaborative effort between Dr. Seema R. Lalani, a physician-scientist at BCM and Dr. Jill V. Hunter, professor of radiology at BCM and Texas Children’s Hospital. They were able to identify the chromosomal deletion responsible for these children’s language delay as well as structural brain changes.
According to Lalani, “I got intrigued when I kept seeing this small (genomic) change in children from a large sample of more than 15,000 children referred for chromosomal microarray analysis at Baylor College of Medicine. These children were predominantly Burmese refugees or of Vietnamese ancestry living in the United States. It started with two children whom I evaluated at Texas Children’s Hospital and soon realized that there was a pattern of early language delay and brain imaging abnormalities in these individuals carrying this deletion from this part of the world. Within a period of two to three years, we found 13 more families with similar problems, having the same genetic change. There were some children who obviously were more affected than the others and had cognitive and neurological problems, but many of them were identified as late-talkers who had better non-verbal skills compared to verbal performance.” Using magnetic resonance imaging (MRI), Hunter determined the specific pattern of white matter abnormalities in Southeast Asian decent children and their parents carrying this chromosomal deletion.
Lalani, Hunter and an international group of collaborators have identified a genomic deletion on chromosome 2. This deletion removes part of gene TM4SF20 which codes for a protein that spans the cell membrane. This deletion is associated with bright white spots in white matter of the brain as observed with MRI. Currently, the function of this protein remains a mystery. Lalani believes this deletion could be responsible for early language delay in a large number of children from Southeast Asia.
Dr. James R. Lupski, vice chair of the department of molecular and human genetics at BCM, points out that, “Professor Lalani has made a stunning discovery in that she provides evidence that population-specific intragenic CNV (copy number variation – a deletion or duplication of the chromosome) can contribute to genetic susceptibility of even common complex disease such as speech delay in children.”
Lalani reports that this gene deletion is present in 2 percent of the Vietnamese Kinh population, which happens to make up 90 percent of the population in that country. She goes on to say, “In the 15 families we have identified, all children have early language delay. Some are diagnosed with autism spectrum disorder, and if you do a brain MRI study, you find white matter changes in about 70 percent of them. We have found this change in children who are Vietnamese, Burmese, Thai, Indonesian, Filipino and and Micronesian. It is very likely that children from other Southeast Asian countries within this geographical distribution also carry this genetic change.” Since these children are located within a particular geographical location, Lalani suspects this is an ancient founder effect. In other words, a gene deletion occurred spontaneously in an individual at some point in the past and that deletion was passed on to offspring.
Lalani believes it to be important to observe these children and monitor their develop as they grow, adding that this deletion has been observed in children whose parents were late-talkers, but were able to overcome their difficulties and achieve high levels of success as professionals. Apparently, there is variability within the deletion individuals which peaks one’s interest in terms of genetic and environmental modifiers that bring about observed differences in behavior.
Normal children tend to have 75 to a 100 word vocabulary by 2 years of age, while language delayed children have a vocabulary of 2 to 3 words at 2 years of age. However, evidence suggests that these children can catch up and tend to have better non-verbal skills than verbal. Researchers, at this point, are unable to say whether this trend will hold true over time and it is not entirely clear how this communication problem correlates with observed structural brain changes.