Epilepsy in KCNH1-related syndromes.
KCNH1 mutations have been identified in patients with Zimmermann-Laband syndrome and Temple-Baraitser syndrome, as well as patients with uncharacterized syndromes with intellectual disability and overlapping features. These syndromes include dysmorphic facial features, nail hypo/aplasia, thumb and skeletal anomalies, intellectual disability, and seizures. We report the epilepsy phenotype in patients with KCNH1 mutations. Demographic data, electroclinical features, response to antiepileptic drugs, and results of significant diagnostic investigations of nine patients carrying mutations in KCNH1 were obtained from referring centres. Epilepsy was present in 7/9 patients. Both generalized and focal tonic-clonic seizures were observed. Complete seizure control was achieved with pharmacological treatment in 2/7 patients; polytherapy was required in 4/7 patients. Status epilepticus occurred in 4/7 patients. EEG showed a diffusely slow background in 7/7 patients with epilepsy, with variable epileptiform abnormalities. Cerebral folate deficiency and an increase in urinary hypoxanthine and uridine were observed in one patient. Epilepsy is a key phenotypic feature in most individuals with KCNH1-related syndromes, suggesting a direct role of KCNH1 in epileptogenesis, although the underlying mechanism is not understood.
Pediatric Neurology Division Department of Pediatrics, Child Neurology and Psychiatry, Sapienza-University of Rome, Rome, Italy.
Mario
M
Mastrangelo
Florey Institute and University of Melbourne, Austin Health and Royal Children's Hospital, Melbourne, Australia.
Ingrid E
IE
Scheffer
Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Germany.
Nuria C
NC
Bramswig
Department of Pediatrics, Saveetha Medical College, Chennai, India.
Lal D V
LD
Nair
Department of Pediatrics, University of Washington, Seattle, WA, USA.
Candace T
CT
Myers
Bambino Gesù Children Hospital, Rome, Italy.
Maria Lisa
ML
Dentici
Klinik für Neuropädiatrie, Klinikum Oldenburg, Germany.
Georg C
GC
Korenke
Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, USA.
Kelly
K
Schoch
Department of Pediatrics, University of Montreal, Montreal, Canada.
Philippe M
PM
Campeau
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia, Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.
Susan M
SM
White
Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, USA.
Vandana
V
Shashi
Division of Pediatric Neurology, Department of Pediatrics, Duke University Medical Center, Durham, USA.
Sujay
S
Kansagra
Department of Genetics, University of Groningen, University Medical Center Groningen, The Netherlands.
Anthonie J
AJ
Van Essen
Pediatric Neurology Division Department of Pediatrics, Child Neurology and Psychiatry, Sapienza-University of Rome, Rome, Italy.
Vincenzo
V
Leuzzi
D000015:Abnormalities, Multiple / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use; D001921:Brain / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D019465:Craniofacial Abnormalities / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D004569:Electroencephalography; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D005260:Female; D005351:Fibromatosis, Gingival / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D006214:Hallux / Q000002:abnormalities* / Q000503:physiopathology; D006228:Hand Deformities, Congenital / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D009264:Nails, Malformed / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D013577:Syndrome; D013933:Thumb / Q000002:abnormalities* / Q000503:physiopathology; D055815:Young Adult
D000927:Anticonvulsants; D051638:Ether-A-Go-Go Potassium Channels; C496884:KCNH1 protein, human
KCNH1-related encephalopathy; Temple-Baraitser syndrome; Zimmermann-Laband syndrome; genetic epilepsy; undefined intellectual disability