KMT2E-related neurodevelopmental disorder (KMT2E-NDD; also known as O'Donnell-Luria-Rodan (ODLURO) syndrome) is an autosomal dominant disorder caused by pathogenic variants in the KMT2E gene. Pathogenic variants are typically de novo. Currently, there are no reports of variants inherited from a parent that have been confirmed to be pathogenic. To date, at least 61 individuals have been identified with a pathogenic variant in KMT2E. There is no evidence to indicate that the disease has a higher prevalence in any particular population.
KMT2E-NDD is primarily a neurodevelopmental disorder. Although affected individuals can present with variable features, all have mild to profound developmental delay (DD) or intellectual disability (ID), albeit most individuals fall within the mild range.
Many individuals with KMT2E-NDD may also have the following features, which manifest in infancy or childhood:
● Generalised hypotonia of infancy
● Gastrointestinal symptoms, including vomiting and reduced bowel motility
● Seizures, including febrile seizures
● Autism spectrum disorder (ASD)
● Behavioural issues
● Macrocephaly (often relative macrocephaly to height)
● Microcephaly (in some individuals with missense variants)
● Sleep disturbance, including frequent awakenings and difficult falling asleep
● Minor dysmorphic features
● Variable non-specific brain MRI findings can include:
o Hypoplasia of the corpus callosum
o Ventriculomegaly
o Cerebral cysts
o Delayed myelination
Prognosis: It is unknown whether KMT2E-NDD alters individuals’ life expectancy. One reported individual is alive at age 54, demonstrating that survival into adulthood is possible. Since many adults with a history of neurodevelopmental disease have not undergone current genetic testing (e.g. large gene panel or exome sequencing), it is likely that adults with KMT2E-NDD are currently underrecognized and underreported.
KMT2E