Inheritance: KMT2E-related neurodevelopmental disorder (KMT2E-NDD) is an autosomal dominant disorder. “Autosomal” means that the gene in question is located on one of the numbered, or non-sex, chromosomes. “Dominant” means that the condition is caused when one of the two copies of the gene is altered and any affected individual will have a 50% chance of passing on the condition to each child. KMT2E-NDD is typically caused by a de novo pathogenic variant - a disease-causing variant that has occurred newly in the affected individual and is not inherited from a parent.
Prevalence: To date, over 60 individuals have been reported to have a pathogenic variant in KMT2E. There is no evidence to indicate that the condition occurs more frequently in any particular group.
Clinical features: KMT2E-NDD can affect multiple body systems but mainly involves the neurologic system, which includes the brain and the nerves. Individuals have mild to profound developmental delay (e.g., delayed childhood milestones like walking and talking) or intellectual disability (e.g., learning problems), although it is mild in most individuals, with a few individuals with low normal intelligence
Many individuals with KMT2E-NDD may also have one or more of the following features, which typically begin in infancy or childhood:
● Generalised low tone or “floppy” muscles (also known as hypotonia)
● Gastrointestinal symptoms, including vomiting and reduced bowel motility, constipation
● Seizures, including febrile seizures
● Autism spectrum disorder (ASD)
● Behavioural issues
● Macrocephaly (larger head relative to the body)
● Microcephaly (smaller head relative to the body)
● Sleep disturbance, including frequent awakenings and difficult falling asleep
● Facial features such as prominent/large forehead, deep-set eyes, full cheeks, and prominent nasolabial folds (creases in the skin that run between both sides of the nose to the mouth)
● Minor, nonspecific rain anomalies on MRI imaging, variable
Prognosis: It is unknown whether KMT2E-NDD impacts individuals’ life expectancy. One reported individual is alive at age 54, demonstrating that survival into adulthood is possible. Since many adults with neurodevelopmental delay and/or intellectual disability have not undergone comprehensive genetic testing, it is likely that adults with KMT2E-NDD are currently underrecognized and underreported.
KMT2E