Phenotypic characterization of an older adult male with late-onset epilepsy and a novel mutation in ASXL3 shows overlap with the associated Bainbridge-Ropers syndrome

Abstract

The additional sex combs like 3 gene is considered to be causative for the rare Bainbridge-Ropers syndrome (BRPS), which is characterized by severe intellectual disability, neonatal hypotonia, nearly absent development of speech and language as well as several facial dysmorphisms. Apart from disruptive autistiform behaviors, sleep disturbances and epileptic phenomena may be present. Here, a 47-year-old severely intellectually disabled male is described in whom exome sequencing disclosed a novel heterozygous frameshift mutation in the ASXL3 gene leading to a premature stopcodon in the last part of the last exon. Mutations in this very end 3′ of the gene have not been reported before in BRPS. The phenotypical presentation of the patient including partially therapy-resistant epilepsy starting in later adulthood shows overlap with BRPS, and it was therefore concluded that the phenotype is likely explained by the identified mutation in ASXL3.

Keywords:

• Bainbridge-Ropers syndrome
• ASLX3
• frameshift mutation
• epilepsy
• intellectual disability
• array analysis
• whole exome sequencing
• autism spectrum disorder

Acknowledgments

Written informed consent was obtained from the legal representative (manager of the institute; since no family members are alive) for publication of this paper on the patient and his family and to include a picture of the face of the patient. The patient was referred by the Centre of Consultation and Expertise, region West. The authors are indebted to Mrs Anneke Baselier, consultant psychologist, and to the staff members of the ASVZ-institute for intellectual disabilities for their careful assessment of the behavior status of the patient. Thanks are extended to Mrs Linde van Dongen, psychologist from the Centre of Excellence for Neuropsychiatry of the Vincent van Gogh Institute for Psychiatry, who performed neuropsychological testing.

Disclosure

The authors report no conflicts of interest in this work.