A large study published in the Journal of Speech, Language, and Hearing Research systematically analyzes the genes that have so far been proposed to be involved in specific reading disability (SRD) — commonly called dyslexia, a term the authors consider inappropriate.

Questions about the genetic origins of SRD first arose in 1983. Since then, scientists have wondered whether reading problems stem from specific genes that emerged during human evolution or from a much older genetic basis.

The study suggests SRD originates from subtle alterations in very ancient genetic networks that predate modern humans and are shared by many vertebrates. Those networks are central to brain development and synaptic transmission, which helps explain why SRD often coexists with other neurodevelopmental disorders.

40 Years of Genomics

Through an extensive literature review, the authors compiled 175 genes reported over the past 40 years as linked to SRD or related processes. The candidate genes were then analyzed using bioinformatic tools and genomic databases to determine each gene’s evolutionary age and function. The analysis went beyond identification to examine patterns of gene expression across different brain regions and within various types of neural cells and to assess whether any genes showed signs of recent evolutionary selection in humans.

Most of the genes associated with SRD are, instead, very ancient — tracing back to the dawn of animal evolution. These genes are not specific to humans or primates but are conserved even in distantly related species and perform basic biological functions, especially in brain development.

Analysis of brain gene expression — performed using data from the Allen Brain Atlas — revealed two distinct groups of genes: one active before 24 weeks of gestation and involved in morphologic brain development such as cell growth and axon formation, and the other active later and responsible for neuronal communication and synaptic transmission that underlie cognitive processes.

Single-cell data showed that the same genes linked to SRD are expressed predominantly in excitatory and inhibitory neurons, and are expressed to a much lesser extent in non-neural cells such as glia. Network analysis identified hub genes central to orchestrating complex neural functions. None of these genes showed signs of recent evolution; rather, they are highly conserved, underscoring their vital role in brain function. “These genetic networks show deep conservation and suggest that their original roles in fundamental processes, such as neural organization and brain development, were only later co-opted for human-specific traits, including reading,” the authors explained.

Ancient Genes, Modern Reading

This finding undermines the assumption that the ability to read is a genetic trait developed only in humans. As the authors noted, “The fact that reading is a uniquely human skill, whereas SRD genes are ancient and conserved across species, suggests an intriguing paradox. Our results indicate that although the genetic components that support the (dis)ability to read evolved long before reading itself, those elements alone are not sufficient for acquiring reading. What makes human reading possible does not appear to derive from specialized ‘reading genes’ but rather from how these ancient genetic mechanisms interact within a larger and more complex context, such as the human brain.”

In the 2022-2023 school year, 204,671 students in Italy from the third grade of primary school onward were identified as having dyslexia, 110,937 had dysgraphia, 130,645 had dysorthography, and 121,918 had dyscalculia, according to the Ministry of Education and Merit (Italy’s national agency responsible for collecting and reporting school enrollment and special-education statistics). Dyslexia is the most common learning disorder (36%), with diagnoses often delayed and frequently occurring alongside other disorders.

The study corroborates this finding, suggesting there may be genetic overlap with other neurodevelopmental conditions and highlighting shared neurobiologic pathways that could guide both diagnosis and intervention. Some genes identified in the study are also implicated in other neuropsychiatric disorders and could become targets for new therapeutic strategies.

The genetic connections revealed by the analysis promote a holistic view of SRD. Identifying two functional groups of genes — one active in early morphologic brain development (before 24 weeks’ gestation) and the other involved in subsequent synaptic signaling — suggests SRD can manifest in different neurobiological forms, each with distinct clinical presentations.

Finally, the discovery of a critical window around 24 weeks’ gestation underscores the importance of early screening and intervention to identify children at risk and, where possible, take action before school entry.

This story was translated from Univadis Italy, part of the Medscape Professional Network.