Clinical Guidance
KMT2B-related disorders include KMT2B-related dystonia (DYT-KMT2B) (258 individuals from 229 families) and KMT2B-related neurodevelopmental disorder (NDD) (27 individuals from 25 families). DYT-KMT2B is a complex childhood-onset movement disorder typically characterized by a progressive disease course commonly evolving from lower-limb focal dystonia into generalized dystonia with prominent cervical, cranial, and laryngeal involvement. Communication difficulties secondary to articulation difficulties (dysarthria) and low speech volume (hypophonia) are common. Bulbar dysfunction leads to impaired swallowing with an increased risk of aspiration and gastrostomy tube placement in some. In most individuals, the movement disorder is accompanied by additional neurologic or systemic manifestations, as in complex dystonia. Intellectual disability (ID)/ developmental delay (DD) is common. Neurobehavioral/psychiatric manifestations can include attention-deficit/hyperactivity disorder (ADHD), anxiety, depression, and obsessive-compulsive disorder. Although many affected individuals follow a similar disease course, an increasing number have milder and atypical findings. Atypical first disease presentations include isolated upper limb, neck, trunk, or oromandibular/laryngeal dystonia or dystonic tremor [, , , , , , , , , , , , , , , , , , , , , , , , , , ]. KMT2B-related NDD has been described both in individuals who have family members with an inherited KMT2B pathogenic variant and a dystonic phenotype , as well as in individuals with no family history of a KMT2B-related disorder [, , , , ]. Ten individuals with deletions involving chromosome 19q13.11-19q13.12 encompassing KMT2B presented with mild-to-severe DD/ID [, , , , , ]. Additional neurologic or systemic manifestations included poor weight gain/ short stature, microcephaly, and skin features. To date, about 238 individuals with a pathogenic variant in KMT2B and 33 individuals with deletions on chromosome 19q13.11-19q13.12 encompassing KMT2B have been reported. The following description of the phenotypic features associated with KMT2B-related disorders is based on these reports . Table 2. KMT2B-Related Disorders: Frequency of Select Features Feature | % of Persons w/Feature DYT-KMT2B (n=271) | KMT2B-related NDD (n=26)
Movement disorders | Dystonia | 100% | None |
|---|
Additional movement disorders1 | ~27% | None | — |
Laryngeal dysfunction | ~51% | None | — |
Bulbar or laryngeal dysfunction/ feeding difficulties | ~30%2 | ~44% | — |
Developmental delay | ~26% | ~81% | — |
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Source: GeneReviews — "KMT2B-Related Disorders"
