A case of PSMC5-associated neurodevelopmental proteasomopathy

The patient is an 11-year-old boy with autism, intellectual disability, and ADHD. The pregnancy was complicated by polyhydramnios. He was born at full-term with a birth weight of 3.5 kgs, after an unremarkable neonatal course. Developmental concerns were noted from infancy by the family. He exhibited hypotonia and achieved sitting and crawling between 9 and 12 months of age. He walked at approximately 18 months of age. Regarding language development, he had a few spoken words by age 3 but subsequently experienced language regression, gradually losing these words. He currently has minimal spoken language. Additional medical diagnoses include cerebral visual impairment, ptosis, optic nerve hypoplasia, hearing loss, and a mildly elongated distal transverse aortic arch. Brain MRI at age 2 showed thinning of the corpus callosum, particularly in the splenium region, along with decreased posterior periventricular white matter volume. Exome sequencing revealed a de novo heterozygous missense variant in PSMC5.