Isolated childhood apraxia of speech (ORPHA:209908)
A rare neurologic disease characterized by impaired ability to execute complex coordinated movements underlying the production of speech, leading to highly unintelligible speech in the absence of muscular or sensory deficits.
Epidemiology
The exact prevalence of isolated childhood apraxia of speech (CAS) is unknown. Regarding CAS due to FOXP2 variants, approximately 35 individuals from 11 families with intragenic, pathogenic variants have been described in the literature so far. 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
CAS is characterized by 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 including dysarthria, oral motor dyspraxia, receptive and expressive language impairment, impairment of reading and spelling, global developmental delay, autistic features, and minor facial dysmorphism have been described occasionally for patients with CAS due to FOXP2 variants.
Etiology
The disorder may be idiopathic or due to FOXP2 (7q31.1) haploinsufficiency. FOXP2 (7q31.1) encodes forkhead box protein P2, a member of the forkhead box family of transcription factors. Usually, heterozygous missense variants within the forkhead domain or truncating variants are identified but also larger deletions containing FOXP2 or structural aberrations disrupting FOXP2 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
Differential diagnosis includes syndromic disorders with overlapping, prominent speech and language impairment and a variety of additional clinical aspects (e. g. intellectual disability, epilepsy, growth phenotypes, malformations) and includes 7q31 microdeletion syndrome, 16p11.2 microdeletion syndrome, 7q11.23 duplication syndrome, KANSL1-related intellectual disability syndrome, and GRIN2A-related disorders. CAS, although mostly not isolated, can also occur secondary to intrauterine stroke, infections, or trauma.
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 depends on the underlying cause of CAS. Recurrence risk for CAS due to FOXP2 alterations 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 depends on the underlying cause of CAS. It 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.

                            Last update: 
                            May 2022


                            - Expert reviewer(s): 
                            Dr Melissa RIEGER | ITHACA* - Pr Christiane ZWEIER 


                                * European Reference Network