FOXP2-related speech and language disorder

FOXP2-related speech and language disorder affects the development of speech and language beginning in early childhood. Affected individuals have a condition known as childhood apraxia of speech (CAS), which makes it difficult to produce the sequences of sounds and syllables needed to form words. CAS is caused by abnormalities in the parts of the brain that plan and coordinate the movements of the lips, mouth, and tongue. Children with FOXP2-related speech and language disorder say their first words later than other children, typically between 18 months and 7 years of age. Their speech is often difficult to understand, although the clarity of speech usually improves over time.  

In addition to having problems with producing speech (expressive language), people with FOXP2-related speech and language disorder may have difficulty understanding speech (receptive language). Some affected individuals also have trouble with other language-related skills, such as reading, spelling, and grammar. 

Less commonly, individuals with FOXP2-related speech and language disorder have features of autism spectrum disorder, which is a condition characterized by impaired social skills and communication problems. Some affected individuals have difficulty with motor skills such as walking, writing, or buttoning clothes, but these typically improve with treatment. Some affected individuals may have learning difficulties. 

FOXP2-related speech and language disorder is a rare disorder, although its exact prevalence is unknown. CAS affects approximately 1 to 2 in 1,000 people, but it is thought that FOXP2-related speech and language disorder accounts for only a small portion of these cases.

Variants (also called mutations) in the FOXP2 gene cause FOXP2-related speech and language disorder. The FOXP2 gene provides instructions for making a protein that acts as a transcription factor, which means that it controls the activity of other genes. Researchers suspect that this protein plays an important role in the functioning of synapses, which are the connections between nerve cells (neurons) where cell-to-cell communication occurs.

In people with FOXP2-related speech and language disorder, variants in the FOXP2 gene cause cells to produce an abnormal version of the FOXP2 protein that does not function properly. Because the FOXP2 protein is a transcription factor, changes in the protein's activity affect the activity of other genes in the developing brain. Researchers suspect that many of the genes targeted by the FOXP2 protein play important roles in brain development and the connections between neurons. 

The FOXP2 gene is one of the genes found on chromosome 7. When large deletions or rearrangements of genetic material on this chromosome affect the FOXP2 gene and neighboring genes, it can cause a disorder known as FOXP2-plus-related speech and language disorder. Because other genes are involved, individuals with FOXP2-plus-related speech and language disorder are more likely to have features such as developmental delays and autism spectrum disorder than individuals who only have a variant in the FOXP2 gene. 

FOXP2-related speech and language disorder is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In approximately 50 percent of cases, the condition results from a new (de novo) variant in the gene that occurs during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or during early embryonic development. These affected individuals typically have no history of the disorder in their family.

The inheritance of FOXP2-plus-related speech and language disorder is more complex and depends on the specific genetic change.