KMT2B関連障害におけるオーストリアでの臨床的特徴と深部脳刺激術後の長期予後

Since its initial description in 2016, DYT-KMT2B has emerged as one of the most common genetic causes of early-onset dystonia. Subsequent reports have expanded its phenotypic spectrum, frequently including neurodevelopmental features. Deep brain stimulation of the globus pallidus internus (GPi DBS) has become a therapeutic mainstay; however, most published data are based on single cases or short-term observations, and long-term outcomes remain poorly characterized.

We report the clinical course and response to GPi DBS in nine patients with KMT2B variants prospectively followed at two Austrian national reference centers for rare movement disorders. Long-term follow-up data (range: 5-20 years) were available for six patients. Clinical features and treatment outcomes were compared with previously published cohorts.

Non-motor features such as developmental delay, intellectual disability, and epilepsy were more frequent in our cohort than in earlier reports. All patients developed generalized dystonia and bulbar involvement over time, emphasizing the progressive nature of the disease. Despite secondary symptom worsening during long-term follow-up, GPi DBS preserved ambulation in three patients and enabled sustained recovery of walking ability in two, maintaining functional independence. Surgical correction of foot deformities further supported mobility. Notably, KMT2B variants were identified upon genetic re-evaluation in two patients previously diagnosed with dyskinetic cerebral palsy.

Our long-term data underscore the progressive but heterogeneous course of DYT-KMT2B. GPi DBS offers durable clinical benefits, particularly when initiated before loss of ambulation. Early surgical intervention and multidisciplinary management are essential to optimize long-term outcomes.