Developmental delay and intellectual disability: Almost all individuals with KMT2E-NDD have global developmental delay (i.e., they take longer to reach developmental milestones than other children their age). The majority can communicate by speaking (i.e., are verbal), but individuals can have delayed speech with or without problems making certain sounds (i.e., articulation issues). All reported individuals are able to walk independently, although many were delayed in achieving this milestone, and most presented with additional motor delays. The majority of affected individuals had intellectual disability, usually in the mild to moderate range.
Seizures: There is no consistent seizure type or epilepsy syndrome described in individuals with KMT2E-NDD. The presence of epilepsy may be related to the type of genetic variant. Sex-related differences have also been noted: epilepsy has been noted in 43% of females but in only 5% of males.
Autism: Autism is seen more frequently in males with KMT2E-NDD. No females have yet been reported to have autism.
Musculoskeletal features: Muscle weakness is seen in about 46% of individuals with KMT2E-NDD. Loose joints or joint hypermobility has also been reported.
Behavioural problems: Apart from autism, a few individuals have behavioural concerns such as skin-picking, aggression, anxiety, and sensory issues. At least two individuals have been diagnosed with attention-deficit/hyperactivity disorder (ADHD).
Growth: Growth parameters are variable for individuals, but most are in the normal range for height and weight, both at birth and later in life.
Gastrointestinal issues: Gastrointestinal symptoms have been reported in almost 50% of affected individuals and include reflux, vomiting, or constipation reduced bowel motility resulting in constipation.
Sleep disturbance: Sleep issues have been reported in approximately 47% of affected individuals and include frequent awakening and difficulties falling asleep.
Facial features: No characteristic pattern of facial features has been observed across individuals with KMT2E-NDD. Facial features are seen in a subset of individuals and commonly include larger head , large forehead, deep-set eyes and prominent cheeks.
Neuroimaging: Approximately 20% of affected showed nonspecific anomalies on brain imaging.