Objective: Determining the genetic etiology of childhood-onset dystonia is important for making the right treatment decisions, prognostic prediction, and genetic counseling.
Methods: A multi-center study was conducted to define the clinical spectrum and genetic landscape in a cohort of patients with genetically confirmed childhood-onset primary dystonia.
Results: We identified 64 patients (female:32 male:32) from 17 centers. Mutations were detected in a total of 22 genes, the most common being in KMT2B (20%), SLC2A1 (12,5%), TOR1A (11%), and GNAO1 (9%) (Figure 1). The genetic analyses leading to the diagnosis were whole-exome sequencing (53%), single-gene analysis (25%), gene panels (20%), and microarray (2%).
The onset of dystonia varied between the newborn period and 13 years (median:5 years). Dystonia was generalized in 53% (n=34), multifocal in 22% (n=14), focal in 14% (n=9), segmental in 9% (n=6) and hemidystonic in 2% (n=1) of the patients. The majority of patients had limb dystonia (92%), while the trunk was involved in 44% (n=28), the neck in 42% (n=27) and the face in 17% (n=11) of the patients.
Accompanying movement disorders were choreathetosis(n=13), ataxia(n=12), tremor(n=10), myoclonus(n=8), parkinsonism(n=5), tics(n=2), and ballismus(n=1). The most frequent comorbidities seen in this cohort were; delayed motor development (58%), intellectual disability (52%), epilepsy (22%), dysmorphic features (22%),and psychiatric diseases (8%).
Conclusion: KMT2B, SLC2A1, TOR1A, and GNAO1 were the most common genes found responsible for childhood-onset dystonia in this cohort. The majority of patients had accompanying signs and associated features indicating the need for substantial neurological evaluation in patients presenting with dystonia.
Keywords: dystonia, movement disorders
Sanem Yilmaz
Ege University Medical Faculty
Turkey
Esra Serdaroglu
Gazi University Medical Faculty
Turkey
Bulent Kara
Kocaeli University Medical Faculty
Turkey
Ilknur Erol
Baskent University Adana Medical and Research Center Faculty of Medicine, Division of Pediatric Neurology
Turkey
Uluc Yis
Dokuz Eylul University Medical Faculty
Turkey
Seda Kanmaz
Ege University Medical Faculty
Turkey
Deniz Yuksel
Ege University Medical Faculty
Turkey
Mehmet Canpolat
Erciyes University Medical Faculty
Turkey
Mustafa Komur
Mersin University Medical Faculty
Turkey
Nese Citak Kurt
Yıldırım Beyazıt University Faculty of Medicine, Ankara City Hospital, Department of Pediatrics, Division of Pediatric Neurology, Ankara, Turkey.
Turkey
Omer Bektas
Ankara University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Serkan Kirik
Fırat University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Ayse Aksoy
Ondokuz Mayıs University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Cisil Cerci Kubur
Celal Bayar University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Nihal Olgac dundar
Izmir Katip Celebi University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Olcay Gungor
Pamukkale University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Tulay Kamasak
Karadeniz Technical University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Cemile Busra Olculu
Ege University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Seyda Besen
Baskent University Adana Medical and Research Center Faculty of Medicine, Division of Pediatric Neurology
Turkey
Deniz Sünnetçi Akkoyunlu
Kocaeli University Faculty of Medicine, Department of Medical Genetics, Kocaeli, Turkey.
Turkey
Didem Soydemir
Dokuz Eylül University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Hale Atalay Celik
University of Health Sciences Turkey, Dr. Sami Ulus Research and Training Hospital, Department of Pediatrics, Division of Pediatric Neurology, Anka
Turkey
Hakan Gumus
Erciyes University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Didem Ardıclı
Ankara City Hospital Department of Pediatric Neurology, Üniversiteler Mahallesi 1604. Cadde No: 9 Çankaya
Turkey
Mirac Yildirim
Ankara University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Leman Tekin Orgun
Baskent University Adana Medical and Research Center Faculty of Medicine, Division of Pediatric Neurology
Turkey
Huseyin Per
Erciyes University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Semra Hız
Dokuz Eylül University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Cetin Okuyaz
Mersin University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Banu Anlar
Hacettepe University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Neurology
Turkey
Hasan Tekgul
Ege University Medical Faculty, Department of Pediatrics, Division of Pediatric Neurology
Turkey
