KMT2B

Clinical Characteristics

The clinical phenotype is of an early onset progressive dystonia, which typically begins in the lower limbs. The dystonia becomes generalised over time (range 1-9 years), often with prominent cervical (retrocollis and torticollis), oromandibular (facial dystonia, and bulbar-oromandibular) and laryngeal (dysphonia and spasmodic laryngeal spasm) involvement. Bulbar features are often predominant and present in the majority.

Dysmorphic features of an elongated face, broad nasal base, bulbous nasal tip, fifth-finger clinodactyly or second and third syndactyly have been identified in some patients, and more frequently in those with microdeletions and predicted truncating variants.

Additional features include preceding developmental delay (38%), intellectual disability (ID) (57%, mild to severe), microcephaly (21% of cohort, only reported in patients with loss-of-function intragenic variants and microdeletions) and short stature (21%).

Dermatological (cutis aplasia, abnormal scarring), systemic (renal and respiratory), ophthalmological (oculomotor apraxia, strabismus) and psychiatric (ADHD, autism, anxiety) symptoms are also reported in some individuals.

Atypical movement disorder phenotypes are reported in association with KMT2B variants, including, dystonia presenting in later in adulthood, paroxysmal cervical dystonia only, oromandibular dystonia with no lower limb dystonia, or dystonia only involving the lower limbs.

MRI features are subtle, with some patients showing symmetrical hypointensity of the globus pallidi (especially the lateral aspect of the globus pallidus externa) on T2, diffusion and susceptibility weighted images.