We performed a search on Pubmed and OVID/medline databases for additional cases of CNOT9 pathogenic variant in patients with neurodevelopmental disorders.

Our patient is >twice the age of prior probands, referred increased aggressive behaviors and difficulty dressing concerning for cognitive decline. She has facial dysmorphisms of almond-shaped eyes and prominent teeth. She has intellectual developmental delay (DD) and well-controlled epilepsy but holds a janitorial job. Mini-Mental State Exam scored 12/30. Her mother reportedly had similar intellectual function though did not undergo testing before death age >80.

Seven cases have been found and reviewed in addition to our case.  There were 2 males and 6 females. Median age was 14.5 years (range 6 to 51). All 8 individuals demonstrated moderate to severe DD and nonspecific facial dysmorphisms. Speech delay was noted in 4 individuals having absent/almost absent speech. Seizures were noted in 6 out of the 8 individuals during their lifetime, with or without a diagnosis of epilepsy.

To our knowledge, this is the first case reporting CNOT9 phenotype mutation in late adulthood. All other previous cases were pre-teens, teenagers or young adults. Penetrance of de novo variants of CNOT9 mutation due to the autosomal dominant inheritance is not known. Questions of fertility and natural history in adulthood are also unanswered. Further longitudinal studies of known cases are required to better appreciate the phenotypic spectrum of this mutation.