arXiv Open Access 2025

KMT2B-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation

L Cif D Demailly JP Lin KE Barwick M Sa +110 lainnya

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Abstrak

Heterozygous mutations in KMT2B are associated with an early-onset, progressive, and often complex dystonia (DYT28). Key characteristics of typical disease include focal motor features at disease presentation, evolving through a caudocranial pattern into generalized dystonia, with prominent oromandibular, laryngeal, and cervical involvement. Although KMT2B-related disease is emerging as one of the most common causes of early-onset genetic dystonia, much remains to be understood about the full spectrum of the disease. We describe a cohort of 53 patients with KMT2B mutations, with detailed delineation of their clinical phenotype and molecular genetic features. We report new disease presentations, including atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype. In addition to the previously reported systemic features, our study has identified co-morbidities, including the risk of status dystonicus, intrauterine growth retardation, and endocrinopathies. Analysis of this study cohort (n = 53) in tandem with published cases (n = 80) revealed that patients with chromosomal deletions and protein-truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants. Eighteen individuals had detailed longitudinal data available after insertion of deep brain stimulation for medically refractory dystonia. Median age at deep brain stimulation was 11.5 years (range: 4.5 to 37.0 years). Follow-up after deep brain stimulation ranged from 0.25 to 22 years. Significant improvement of motor function and disability (as assessed by the Burke-Fahn-Marsden Dystonia Rating Scales, BFMDRS-M and BFMDRS-D) was evident at 6 months, 1 year, and last follow-up (motor, P = 0.001, P = 0.004, and P = 0.012; disability, P = 0.009, P = 0.002, and P = 0.012).

Topik & Kata Kunci

q-bio.NC

Penulis (115)

L Cif

D Demailly

JP Lin

KE Barwick

M Sa

L Abela

S Malhotra

WK Chong

D Steel

A Sanchis-Juan

A Ngoh

N Trump

E Meyer

X Vasques

J Rankin

MW Allain

CD Applegate

S Attaripour Isfahani

J Baleine

B Balint

JA Bassetti

EL Baple

KP Bhatia

C Blanchet

L Burglen

G Cambonie

EC Seng

SC Bastaraud

F Cyprien

C Coubes

V d'Hardemare

Deciphering Developmental Disorders Study

A Doja

N Dorison

D Doummar

ME Dy-Hollins

E Farrelly

DR Fitzpatrick

C Fearon

EL Fieg

BL Fogel

EB Forman

RG Fox

Genomics England Research Consortium

WA Gahl

S Galosi

V Gonzalez

TD Graves

A Gregory

M Hallett

H Hasegawa

SJ Hayflick

A Hamosh

M Hully

S Jansen

SY Jeong

JB Krier

S Krystal

KR Kumar

C Laurencin

H Lee

G Lesca

LL François

T Lynch

N Mahant

JA Martinez-Agosto

C Milesi

KA Mills

M Mondain

H Morales-Briceno

NIHR BioResource

JR Ostergaard

S Pal

JC Pallais

F Pavillard

PF Perrigault

AK Petersen

G Polo

G Poulen

T Rinne

T Roujeau

C Rogers

A Roubertie

M Sahagian

E Schaefer

L Selim

R Selway

N Sharma

R Signer

AG Soldatos

DA Stevenson

F Stewart

M Tchan

Undiagnosed Diseases Network

IC Verma

BBA de Vries

JL Wilson

DA Wong

R Zaitoun

D Zhen

A Znaczko

RC Dale

CM de Gusmão

J Friedman

VSC Fung

MD King

SS Mohammad

L Rohena

JL Waugh

C Toro

FL Raymond

M Topf

P Coubes

KM Gorman

MA Kurian

Format Sitasi

APA MLA BibTeX

Cif, L., Demailly, D., Lin, J., Barwick, K., Sa, M., Abela, L. et al. (2025). KMT2B-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation. https://arxiv.org/abs/2502.06320

@article{cif2025, author = {L Cif and D Demailly and JP Lin and KE Barwick and M Sa and L Abela and S Malhotra and WK Chong and D Steel and A Sanchis-Juan and A Ngoh and N Trump and E Meyer and X Vasques and J Rankin and MW Allain and CD Applegate and S Attaripour Isfahani and J Baleine and B Balint and JA Bassetti and EL Baple and KP Bhatia and C Blanchet and L Burglen and G Cambonie and EC Seng and SC Bastaraud and F Cyprien and C Coubes and V d'Hardemare and Deciphering Developmental Disorders Study and A Doja and N Dorison and D Doummar and ME Dy-Hollins and E Farrelly and DR Fitzpatrick and C Fearon and EL Fieg and BL Fogel and EB Forman and RG Fox and Genomics England Research Consortium and WA Gahl and S Galosi and V Gonzalez and TD Graves and A Gregory and M Hallett and H Hasegawa and SJ Hayflick and A Hamosh and M Hully and S Jansen and SY Jeong and JB Krier and S Krystal and KR Kumar and C Laurencin and H Lee and G Lesca and LL François and T Lynch and N Mahant and JA Martinez-Agosto and C Milesi and KA Mills and M Mondain and H Morales-Briceno and NIHR BioResource and JR Ostergaard and S Pal and JC Pallais and F Pavillard and PF Perrigault and AK Petersen and G Polo and G Poulen and T Rinne and T Roujeau and C Rogers and A Roubertie and M Sahagian and E Schaefer and L Selim and R Selway and N Sharma and R Signer and AG Soldatos and DA Stevenson and F Stewart and M Tchan and Undiagnosed Diseases Network and IC Verma and BBA de Vries and JL Wilson and DA Wong and R Zaitoun and D Zhen and A Znaczko and RC Dale and CM de Gusmão and J Friedman and VSC Fung and MD King and SS Mohammad and L Rohena and JL Waugh and C Toro and FL Raymond and M Topf and P Coubes and KM Gorman and MA Kurian}, title = {KMT2B-related disorders: expansion of the phenotypic spectrum and long-term efficacy of deep brain stimulation}, year = {2025}, journal = {arXiv}, url = {https://arxiv.org/abs/2502.06320}, }

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Tahun Terbit: 2025
Bahasa: en
Sumber Database: arXiv
Akses: Open Access ✓