FOXP2

Parents

Clinical features
FOXP2-related conditions share a core speech disorder phenotype known as childhood apraxia of speech (CAS). This speech disorder affects the production, sequencing, timing, and stress of sounds, syllables, and words. Children with CAS have difficulty in acquiring speech, with delayed onset of first words and a protracted period of speech development relative to peers. For children with CAS, once speech is acquired, it is characterised by an inability to automatically and accurately sequence speech sounds into syllables, syllables into words, and words into sentences with correct prosody. The condition changes across the lifespan with features of CAS resolving to some degree over time, but fluent and intelligible speech production remains a core challenge for affected adults.

In FOXP2-only-related disorders, nonverbal (performance) IQ is typically more preserved compared to verbal IQ. Fine motor skills may be impaired (e.g., buttoning clothes, tying shoelaces), yet gross motor skills are normal. Autistic features and dysmorphic findings have been reported in a small number of affected individuals. In FOXP2-plus-related disorders, oral motor deficits, global developmental delay, and autism spectrum disorder are more common. Not all individuals with a mutation in FOXP2 show these features. A list of further clinical features experienced by individuals with FOXP2-related conditions is provided in the Parents – Clinical characteristics section.

Prevalence
Epidemiological studies have not been conducted on FOXP2, but the core phenotype associated with this condition, CAS, occurs with an estimated prevalence of 1-2:1000 population. No data are available to determine what proportion of CAS is caused by disruptions of FOXP2. In a cohort with a severe speech disorder, one of 49 individuals had a confirmed FOXP2-related speech and language disorder, whereas previously unreported FOXP2 variants of uncertain clinical significance were detected in two additional unrelated individuals. In an independent cohort with a CAS diagnosis, a previously unreported FOXP2 variant of uncertain clinical significance was detected in one of 24 individuals.

Inheritance
Genetic counseling for a FOXP2-related speech and language disorders depends on the causative genetic alteration:

  • Large non-recurrent contiguous gene deletion that includes FOXP2; 80% are de novo and the remainder are inherited in an autosomal dominant manner.
  • Sequence variant within FOXP2; ~70% are de novo and the remainder are inherited in an autosomal dominant manner.
  • Maternal uniparental disomy of chromosome 7 (UPD7); recurrence risk is not increased over that of the general population.
  • Structural variant (e.g., chromosome translocation, inversion) that disrupts FOXP2; recurrence risk depends on the specific structural variant.

For further information on genetic counselling, see Parents – Molecular characteristics section.