Epilepsy in KCNH1-related syndromes

Mario Mastrangelo, Ingrid E. Scheffer, Nuria C. Bramswig, L. D V Nair, Candace T. Myers, Maria Lisa Dentici, Georg C. Korenke, Kelly Schoch, Philippe M. Campeau, Susan M. White, Vandana Shashi, Sujay Kansagra, Anthonie J. Van Essen, Vincenzo Leuzzi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Aim. 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. Methods. 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. Results. 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. Conclusions. 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.

Original languageEnglish
Pages (from-to)123-136
Number of pages14
JournalEpileptic Disorders
Volume18
Issue number2
DOIs
Publication statusPublished - Jun 1 2016

Fingerprint

Epilepsy
Epilepsy, Partial, Motor
Seizures
Intellectual Disability
Mutation
Hypoxanthine
Status Epilepticus
Uridine
Thumb
Nails
Folic Acid
Anticonvulsants
Electroencephalography
Demography
Pharmacology
Phenotype

Keywords

  • Genetic epilepsy
  • KCNH1-Related encephalopathy
  • Temple-baraitser syndrome
  • Undefined intellectual disability
  • Zimmermann-laband syndrome

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Mastrangelo, M., Scheffer, I. E., Bramswig, N. C., Nair, L. D. V., Myers, C. T., Dentici, M. L., ... Leuzzi, V. (2016). Epilepsy in KCNH1-related syndromes. Epileptic Disorders, 18(2), 123-136. https://doi.org/10.1684/epd.2016.0830

Epilepsy in KCNH1-related syndromes. / Mastrangelo, Mario; Scheffer, Ingrid E.; Bramswig, Nuria C.; Nair, L. D V; Myers, Candace T.; Dentici, Maria Lisa; Korenke, Georg C.; Schoch, Kelly; Campeau, Philippe M.; White, Susan M.; Shashi, Vandana; Kansagra, Sujay; Van Essen, Anthonie J.; Leuzzi, Vincenzo.

In: Epileptic Disorders, Vol. 18, No. 2, 01.06.2016, p. 123-136.

Research output: Contribution to journalArticle

Mastrangelo, M, Scheffer, IE, Bramswig, NC, Nair, LDV, Myers, CT, Dentici, ML, Korenke, GC, Schoch, K, Campeau, PM, White, SM, Shashi, V, Kansagra, S, Van Essen, AJ & Leuzzi, V 2016, 'Epilepsy in KCNH1-related syndromes', Epileptic Disorders, vol. 18, no. 2, pp. 123-136. https://doi.org/10.1684/epd.2016.0830
Mastrangelo M, Scheffer IE, Bramswig NC, Nair LDV, Myers CT, Dentici ML et al. Epilepsy in KCNH1-related syndromes. Epileptic Disorders. 2016 Jun 1;18(2):123-136. https://doi.org/10.1684/epd.2016.0830
Mastrangelo, Mario ; Scheffer, Ingrid E. ; Bramswig, Nuria C. ; Nair, L. D V ; Myers, Candace T. ; Dentici, Maria Lisa ; Korenke, Georg C. ; Schoch, Kelly ; Campeau, Philippe M. ; White, Susan M. ; Shashi, Vandana ; Kansagra, Sujay ; Van Essen, Anthonie J. ; Leuzzi, Vincenzo. / Epilepsy in KCNH1-related syndromes. In: Epileptic Disorders. 2016 ; Vol. 18, No. 2. pp. 123-136.
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AU - Myers, Candace T.

AU - Dentici, Maria Lisa

AU - Korenke, Georg C.

AU - Schoch, Kelly

AU - Campeau, Philippe M.

AU - White, Susan M.

AU - Shashi, Vandana

AU - Kansagra, Sujay

AU - Van Essen, Anthonie J.

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AB - Aim. 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. Methods. 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. Results. 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. Conclusions. 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.

KW - Genetic epilepsy

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