GeneReviews(®)
Book. 1993
Authors: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Fong CT, Mefford HC, Smith RJH, Stephens K
Abstract
CLINICAL CHARACTERISTICS: All FOXP2-related speech and language disorders, regardless of the underlying genetic alteration, have a core phenotype: childhood apraxia of speech (CAS), a disorder of speech motor programming or planning that affects the production, sequencing, timing, and stress of sounds, syllables, and words. All individuals with CAS – whether caused by an alteration of FOXP2 or of an unknown cause – have difficulties in automatically and accurately sequencing speech sounds into syllables, syllables into words, and words into sentences with the correct prosody. Additional findings in FOXP2-related speech and language disorders can include oral motor dyspraxia (difficulty planning or programming oral movements on command); dysarthria (a neuromuscular-based speech disorder that may affect nasal resonance, voice quality, prosody, and breath support for speech); moderate to severe receptive and expressive language disorder; and reading and spelling impairments. The underlying genetic cause of FOXP2-related speech and language disorders is either disruption of FOXP2 only (referred to in this GeneReview as FOXP2-only-related speech and language disorder) or large copy number variants (i.e., contiguous gene deletions), structural variants (i.e., chromosome translocation or inversion), or maternal uniparental disomy of chromosome 7 (UPD7) involving FOXP2 (here referred to as FOXP2-plus speech and language disorders). The genetic alteration determines if only speech and language problems are present (FOXP2-only-related speech and language disorder) or if more global developmental and behavioral issues are likely to be present as well (FOXP2-plus speech and language disorder). In FOXP2-only-related disorders, nonverbal (performance) IQ is typically relatively preserved compared to verbal IQ and fine or gross motor skills are normal. In FOXP2-plus-related disorders oral motor deficits, global developmental delay, and autism spectrum disorder are common.
DIAGNOSIS/TESTING: The diagnosis of a FOXP2-related speech and language disorder is established in a proband by detection of one of the following: A large non-recurrent contiguous gene deletion that includes FOXP2 (58% of affected individuals). A sequence variant within FOXP2 (~21%). Maternal uniparental disomy of chromosome 7 (UPD7) that reduces FOXP2 expression (~12%). A structural variant (e.g., chromosome translocation, inversion) that disrupts FOXP2 (~8%).
MANAGEMENT: Treatment of manifestations: Optimally management of the speech and/or language disorder is determined by a speech pathologist based on the individual's findings (typically: presence and severity of CAS, dysarthria, language deficits, and literacy impairments). A clinical psychologist or neuropsychologist may provide strategies to help manage deficits in specific cognitive domains and an occupational therapist and physiotherapist can provide strategies to help with fine and gross motor deficits. Surveillance: Follow-up evaluations with standardized tests by a speech and language pathologist. Evaluation of relatives at risk: Clarification of the genetic status of presymptomatic relatives at risk identifies as early as possible those who would benefit from prompt evaluation for speech and language disorders and initiation of treatment.
GENETIC COUNSELING: Recurrence risk for sibs of proband with a FOXP2-related speech and language disorder depends on the genetic alteration: Non-recurrent contiguous gene deletions (80% are de novo and the remainder are inherited in an autosomal dominant manner). FOXP2 sequence variants (~70% are de novo and the remainder are inherited in an autosomal dominant manner). Maternal UPD7 (no increased risk to sibs). A structural variant (e.g., chromosome translocation, inversion. If one parent has a structural variant, the risk to sibs is increased and depends on the specific structural variant.) Prenatal testing and preimplantation genetic diagnosis are possible if the causative genetic alteration has been identified in an affected family member.
PMID: 27336128
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