Particular musical aptitude in a female patient with speech disorders: analysis of a de novo FOXP1 truncating mutation and possible role in song-learning.

Heterozygous mutations in forkhead box protein 1 (FOXP1) gene have been shown to cause developmental verbal dyspraxia and language impairment. The FOXP1 protein is a member of the forkhead-box family of transcription factors characterized by a highly conserved forkhead DNA-binding domain (FOX), with a crucial role in language development and song perception. A mechanism of loss of function and haploinsufficiency seems to be the common feature of all mutations associated with FOXP1 disorders. Here we present a young female patient, now thirteen years old, with speech impairment carrying a novel truncating FOXP1 mutation identified by WES analysis. She is the only child of unrelated parents. The family history is positive about neurological or neurobehavioral disorders in the two branches of parental derivation. She presented a delay in the acquisition of the stages of psychomotor development and began a diagnostic process by carrying out standard karyotype (46,XX) and array-CGH analysis, which did not show significant rearrangements.At our last clinical examination, she presented occipitofrontal circumference 54.5 cm (50th-75th centile) vs weight 45,5 kg (25th centile) and height 154 cm (25th centile); cubitus valgus was present. In comparison to so far reported patients identified carrying deleterious FOXP1 mutations, we highlighted her particular ability to perceive and understand intensity, pitch, timbre and tone duration, as well as the rhythm and structure of music (musical aptitude). A number of studies have reported an overlap between the neural and behavioural resources of language and music, suggesting a common evolutionary background of language and musical abilities. Nevertheless, the biological interpretation of the functional impact of this mutation on music-related phenotype capacities is completely unknown. Since to our knowledge this is the first case of FOXP1 mutation associated with musical aptitude, the recruitment of additional cases is mandatory in order to shed light on the peculiar role of this conserved gene in speech and song-learning.