Speech and language impairment and oromotor dyspraxia due to deletion of 7q31 that involves FOXP2

Abstract

We report detailed clinical, cytogenetic, and molecular findings in a girl with a deletion of chromosome 7q31-q32. This child has a severe communication disorder with evidence of oromotor dyspraxia, dysmorphic features, and mild developmental delay. She is unable to cough, sneeze, or laugh spontaneously. Her deletion is on the paternally inherited chromosome and includes the FOXP2 gene, which has recently been associated with speech and language impairment and a similar form of oromotor dyspraxia in at least three other published cases. We hypothesize that our patient's communication disorder and oromotor deficiency are due to haploinsufficiency for FOXP2 and that her dysmorphism and developmental delay are a consequence of the absence of the other genes involved in the microdeletion. We propose that this patient, together with others reported in the literature, may define a new contiguous gene deletion syndrome encompassing the 7q31-FOXP2 region. Cytogenetic and molecular analysis of this region should be considered for other individuals displaying similar characteristics.

Childhood Apraxia of Speech (CAS) in two patients with 16p11.2 microdeletion syndrome

“…The most significant finding, to date, has been the identification of a mutation in the forkhead-box P2 (FOXP2) gene as the source of CAS in approximately half of the widely cited, multigenerational 'KE' pedigree. 14,15 Detection of additional affected individuals with translocations affecting the FOXP2 locus and point mutations in the coding sequence of the gene have confirmed its role in speech [16][17][18][19] and language 20 impairment. Mice that carry heterozygous mutations equivalent to those in affected members of the KE family have deficits in learning rapid motor sequences, as well as impaired synaptic plasticity in corticostriatal and cerebellar circuits.…”

Rearrangements of the Williams–Beuren syndrome locus: molecular basis and implications for speech and language development

“…Although the children with 7q11.23 duplication identified so far have not undergone detailed orofacial movement and oral praxis testing, they do not appear to show any obvious problem with motor coordination of the lower face muscles or tongue, although mild gross motor coordination difficulties were reported in some. This is in contrast to most patients with disruption of FOXP2, who have problems with sneezing, throat clearing and coughing and are sometimes unable to blow their noses (Refs 106,108,110 The study of WBS is unlikely to be as fruitful as the study of 7q11.23 duplication syndrome for advancing our understanding of the genetics of language impairment. Although the language abilities of most children with WBS are lower than would be expected for their CA, these abilities are typically at or slightly above the level that would be expected for their overall intellectual ability (Refs 6,20).…”

Insights into the Genetic Foundations of Human Communication

“…Affected members of the family carry a heterozygous missense mutation in the FOXP2 gene, which encodes a transcription factor that regulates expression of other genes (Lai et al 2001). Several additional cases of CAS related to FOXP2 haploinsufficiency have been reported (Feuk et al 2006;Zeesman et al 2006;Lennon et al 2007;Shriberg et al 2006;MacDermot et al 2005;Turner et al 2013;Laffin et al 2012;Rice et al 2012;Palka et al 2012). The cellular and neurobiological functions of FOXP2 have been explored using a range of in vitro and in vivo approaches (see Bridging the gap between genes and language: FOXP2 as a case study).…”