Pallidal deep brain stimulation response in two siblings with atypical adult-onset dystonia related to a KMT2B variant

Buzo, E. Luque; Casa-Fages, Beatriz De la; Sanchéz, M. González; Sánchez, J.R. Pérez; Carballal, Carlos Fernández; Vidorreta, J. Garbizu; Sierra, Olga Mateo; Chicote, A. Contreras; Grandas, Francisco

doi:10.1016/j.jns.2022.120295

Cited by 2 publications

(4 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several adult and pediatric patients underwent GPi-DBS due to DYT- THAP1 and DYT- KMT2B . Although the number of pediatric patients was lower, the results prove that bilateral GPi-DBS is a valuable therapeutic option for DYT- THAP1 ( 8 – 16 ) and DYT- KMT2B , particularly for movement disorders and regaining mobility, but less so for speech issues ( 5 , 22 – 37 ) ( Supplementary Tables 1 , 2 ). So far, the aforementioned patients presented with severe dystonic postures, majorly impacting their quality of life, as well as those of their families and caregivers.…”

Section: Discussionmentioning

confidence: 90%

“…Further clinical characteristics, such as cognitive disability, psychiatric comorbidities, and dysmorphic features, have been reported in several patients ( 27 – 29 ). Bilateral GPi-DBS has been reported as an efficient therapeutic option, especially for improving movement disorder and regaining independent mobility ( 5 , 22 – 37 ). GPi-DBS is sometimes associated with “dramatic” amelioration in gait but more commonly associated with truncal dystonia and scoliosis; it is rarely associated with speech dysfunction in severely affected patients with KMT2B gene mutations prior to DBS ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

“…Although it is suggested that DBS should be considered as a treatment approach in pharmacoresistent DYT- THAP1 early in childhood to prevent more severe symptoms, such as disabling motor development and quality of life decline, including emotional and social aspects, the results are missing. Additionally, bilateral GPi-DBS has been reported as a valuable therapeutic option for DYT- KMT2B , especially for regaining motor function and mobility, but less so for speech if significant speech difficulties are developed ( 5 , 22 – 37 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

GPi DBS treatment outcome in children with monogenic dystonia: a case series and review of the literature

et al. 2023

View full text Add to dashboard Cite

IntroductionDystonia is the third most common pediatric movement disorder and is often difficult to treat. Deep brain stimulation (DBS) of the internal pallidum (GPi) has been demonstrated as a safe and effective treatment for genetic dystonia in adolescents and adults. The results of DBS in children are limited to individual cases or case series, although it has been proven to be an effective procedure in carefully selected pediatric cohorts. The aim of our study was to present the treatment outcome for 7- to 9-year-old pediatric patients with disabling monogenic isolated generalized DYT-THAP1 and DYT-KMT2B dystonia after bilateral GPi-DBS.Patients and resultsWe present three boys aged <10 years; two siblings with disabling generalized DYT-THAP1 dystonia and a boy with monogenic-complex DYT-KMT2B. Dystonia onset occurred between the ages of 3 and 6. Significantly disabled children were mostly dependent on their parents. Pharmacotherapy was inefficient and patients underwent bilateral GPi-DBS. Clinical signs of dystonia improved significantly in the first month after the implantation and continued to maintain improved motor functions, which were found to have improved further at follow-up. These patients were ambulant without support and included in everyday activities. All patients had significantly lower Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS) values, indicating >25% improvement over the first 15 months. However, there was a decline in speech and upper limb function, manifesting with bradylalia, bradykinesia, and dysphonia, which decreased after treatment with trihexyphenidyl.ConclusionAlthough reports of patients with monogenic dystonia, particularly DYT-THAP1, treated with DBS are still scarce, DBS should be considered as an efficient treatment approach in children with pharmacoresistent dystonia, especially with generalized monogenic dystonia and to prevent severe and disabling symptoms that reduce the quality of life, including emotional and social aspects. Patients require an individual approach and parents should be properly informed about expectations and possible outcomes, including relapses and impairments, in addition to DBS responsiveness and related improvements. Furthermore, early genetic diagnosis and the provision of appropriate treatments, including DBS, are mandatory for preventing severe neurologic impairments.

show abstract

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

GPi DBS treatment outcome in children with monogenic dystonia: a case series and review of the literature

et al. 2023

View full text Add to dashboard Cite

show abstract

“…The most common causative mutations were protein-truncating variants ( n = 103, 61.3%), followed by missense variants ( n = 46, 27.4%) and chromosomal deletions ( n = 18, 10.7%). Since that publication, there has been a further expansion of the literature with 18 scientific papers, comprising 60 additional patients with pathogenic, likely pathogenic or VUSs [ 5 , 20 - 36 ]. A single report of a synonymous variant leading to the generation of a premature stop codon resulting in early-onset dystonia has also been published [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

KMT2B-Related Dystonia in Indian Patients With Literature Review and Emphasis on Asian Cohort

Dhar¹,

Holla²,

Kumari³

et al. 2023

JMD

View full text Add to dashboard Cite

ObjectiveaaMutations in the KMT2B gene have been identified in patients previously diagnosed with idiopathic dystonia. Literature on KMT2B-related dystonia is sparse in the Indian and Asian populations.MethodsaaWe report seven patients with KMT2B-related dystonia studied prospectively from May 2021 to September 2022. Patients underwent deep clinical phenotyping and genetic testing by whole-exome sequencing (WES). A systematic literature search was performed to identify the spectrum of previously published KMT2B-related disorders in the Asian subcontinent.ResultsaaThe seven identified patients with KMT2B-related dystonia had a median age at onset of four years. The majority experienced onset in the lower limbs (n = 5, 71.4%), with generalization at a median duration of 2 years. All patients except one had complex phenotypes manifesting as facial dysmorphism (n = 4), microcephaly (n = 3), developmental delay (n = 3), and short stature (n = 1). Magnetic resonance imaging (MRI) abnormalities were present in four cases. WES revealed novel mutations in the KMT2B gene in all patients except one. Compared to the largest cohort of patients with KMT2B-related disorders, the Asian cohort, comprising 42 patients, had a lower prevalence of female patients, facial dysmorphism, microcephaly, intellectual disability, and MRI abnormalities. Protein-truncating variants were more prevalent than missense variants. While microcephaly and short stature were more common in patients with missense mutations, facial dysmorphism was more common in patients with truncating variants. Deep brain stimulation, performed in 17 patients, had satisfactory outcomes.ConclusionaaThis is the largest series of patients with KMT2B-related disorders from India, further expanding the clinico-genotypic spectrum. The extended Asian cohort emphasizes the unique attributes of this part of the world.

show abstract

Pallidal deep brain stimulation response in two siblings with atypical adult-onset dystonia related to a KMT2B variant

Cited by 2 publications

References 10 publications

GPi DBS treatment outcome in children with monogenic dystonia: a case series and review of the literature

GPi DBS treatment outcome in children with monogenic dystonia: a case series and review of the literature

KMT2B-Related Dystonia in Indian Patients With Literature Review and Emphasis on Asian Cohort

Contact Info

Product

Resources

About