In 2017, three individuals with a mutation of the ACTL6A gene were identified. All individuals had speech delay and learning disabilities or intellectual disability. They were all small-for age at birth or had failure to thrive, but growth improved with age. Other symptoms that these individuals have include congenital heart defects, urogenital anomalies (hypospadias, pelviectasis), musculoskeletal defects (digital anomalies, scoliosis and/or joint laxity) and dysmorphic facial features.
Pathogenic variants in the ACTL6A gene can be identified using molecular genetic testing, either directly by sequencing of the ACTL6A gene or by whole exome sequencing. With whole exome sequencing, the entire exome (all genes which are transcribed to RNA) is being scanned and tested for a variety of syndromes, including the syndrome caused by a pathogenic variants in ACTL6A.
Based on the report of the known individuals with the ACTL6A-related syndrome, the following check-ups/therapy are recommended:
- Educational programs to deal with developmental delay and learning disabilities;
- Routine screening and treatment of cardiac, musculoskeletal, renal, and urologic problems.
Pathogenic variants in ACTL6A gene are inherited in an autosomal dominant manner. They can be inherited, or occur as a de novo mutation. Since some individuals may be only mildly affected, the recurrence risk is assumed to be 50% for future pregnancies, especially if one of the parents has a history of learning disabilities or developmental delay. Prenatal testing is technically feasible.