Childhood Apraxia Of Speech
A rare, genetic language disorder characterized by the core phenotype of childhood apraxia of speech (CAS) while also further aspects such as receptive and expressive language impairment or oral motor dyspraxia often occur.
Epidemiology
The exact prevalence is unknown. Up to date, approximately 35 cases from 11 families with intragenic, pathogenic variants in FOXP2 are described worldwide in the literature. Moreover, a few individuals with speech and language disorders and larger deletions on chromosome 7 including FOXP2 or other structural variants in or next to FOXP2 have been reported.
Clinical description
The disorder is characterized by the core phenotype of childhood apraxia of speech, which is defined as the impairment of the precision and consistency of movements underlying speech in the absence of neuromuscular deficits. Initial signs may include absence of babbling or delay of first words during infancy. Additional manifestations regarding speech and language include dysarthria, oral motor dyspraxia, receptive and expressive language impairment, and impairment of reading and spelling. Furthermore, global developmental delay, autistic features, and minor facial dysmorphism have been described occasionally.
Etiology
The disorder is caused by haploinsufficiency of FOXP2 (7q31.1), encoding forkhead box protein P2, a member of the forkhead box family of transcriptions factors. Usually, heterozygous missense variants within the forkhead domain or truncating variants are identified. Furthermore, larger deletions containing FOXP2 or structural aberrations disrupting FOXP2 directly or by positional effects have been reported.
Diagnostic methods
Diagnosis is usually by targeted analysis upon clinical suspicion or by more unbiased approaches such as chromosomal microarray analysis (deletions including FOXP2), multigene panel or exome sequencing.
Differential diagnosis
Although different candidate genes are discussed in the literature, so far there are no other monogenic causes known for similar, isolated speech and language disorders. Syndromic disorders with overlapping, prominent speech and language impairment and a variety of additional clinical aspects (e. g. intellectual disability, epilepsy, growth phenotypes, malformations) include 16p11.2 microdeletion syndrome, 7q11.23 duplication syndrome, KANSL1-related intellectual disability syndrome, GRIN2A-related disorders.
Antenatal diagnosis
In principle possible, if the underlying pathogenic variant in the family is known.
Genetic counseling
Recurrence risk for siblings of an affected individual is low if the pathogenic variant occurred de novo and 50 % if it is inherited from one of the parents. Genetic counseling should be offered.
Management and treatment
A multidisciplinary team including a speech and language pathologist, a pediatrician, an occupational therapist, and a neuropsychologist is required for evaluation of the phenotypic extent and to determine the individual treatment plan. Augmentative and alternative communication (use of sign language, picture boards or computers) may be useful in some cases.
Prognosis
Prognosis is usually good in the context of intragenic FOXP2 variants, as clinical aspects are limited to speech and language impairment in most cases. However, learning disabilities or behavioral abnormalities may additionally occur. Though speech development and intelligibility usually improve over time, a lifelong speech and language impairment might be present. Larger deletions can be associated with more complex phenotypes.