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Case Reports
. 2019 Nov;60(11):e121-e127.
doi: 10.1111/epi.16372. Epub 2019 Oct 20.

The epileptology of GNB5 encephalopathy

Gemma Poke  1 , Chontelle King  1 , Alison Muir  2 , Guillem de Valles-Ibáñez  1 , Michele Germano  3 , Carolina F Moura de Souza  4 , Jasmine Fung  5 , Brian Chung  5 , Cheuk Wing Fung  5 , Cyril Mignot  6 , Adina Ilea  7 , Boris Keren  8 , Anne-Isabelle Vermersch  9 , Suzanne Davis  10 , Thorsten Stanley  1 , Mahendranath Moharir  11 , Peter Kannu  12 , Zhuo Shao  12 , Natascia Malerba  13 , Giuseppe Merla  13 , Heather C Mefford  2 , Ingrid E Scheffer  14 , Lynette G Sadleir  1
Affiliations
Case Reports

The epileptology of GNB5 encephalopathy

Gemma Poke et al. Epilepsia. 2019 Nov.

Abstract

Pathogenic variants in GNB5 cause an autosomal recessive neurodevelopmental disorder with neonatal sinus bradycardia. Seizures or epilepsy occurred in 10 of 22 previously reported cases, including 6 children from one family. We delineate the epileptology of GNB5 encephalopathy. Our nine patients, including five new patients, were from seven families. Epileptic spasms were the most frequent seizure type, occurring in eight of nine patients, and began at a median age of 3 months (2 months to 3 years). Focal seizures preceded spasms in three children, with onset at 7 days, 11 days, and 4 months. One child presented with convulsive status epilepticus at 6 months. Three children had burst suppression on electroencephalography (EEG), three had hypsarrhythmia, and one evolved from burst suppression to hypsarrhythmia. Background slowing was present in all after age 3 years. Magnetic resonance imaging (MRI) showed cerebral atrophy in one child and cerebellar atrophy in another. All nine had abnormal development prior to seizure onset and ultimately had profound impairment without regression. Hypotonia was present in all, with contractures developing in two older patients. All individuals had biallelic pathogenic variants in GNB5, predicted by in silico tools to result in protein truncation and loss-of-function. GNB5 developmental and epileptic encephalopathy is characterized by epileptic spasms, focal seizures, and profound impairment.

Keywords: GNB5; developmental and epileptic encephalopathy; epilepsy; intellectual disability; recessive.

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References

REFERENCES

    1. Lodder EM, De Nittis P, Koopman CD, Wiszniewski W, Moura de Souza CF, Lahrouchi N et al. GNB5 mutations cause an autosomal-recessive multisystem syndrome with sinus bradycardia and cognitive disability. Am J Hum Genet. 2016;99:704-70.
    1. Turkdogan D, Usluer S, Akalin F, Agyuz U, Aslan ES. Familial early infantile epileptic encephalopathy and cardiac conduction disorder: A rare cause of SUDEP in infancy. Seizure. 2017;50:171-72.
    1. Vernon H, Cohen J, De Nittis P, Fatemi A, McClellan R, Goldstein A, et al. Intellectual developmental disorder with cardiac arrhythmia syndrome in a child with compound heterozygous GNB5 variants. Clin Genet. 2018;93:1254-56.
    1. Shamseldin HE, Masuho I, Alenizi A, Alyamani S, Patil DN, Ibrahim N, et al. GNB5 mutation causes a novel neuropsychiatric disorder featuring attention deficit hyperactivity disorder, severely impaired language development and normal cognition. Genome Biol. 2016;17:195.
    1. Malerba N, Towner S, Keating K, Squeo GM, Wilson W, Merla G. A NGS-targeted autism/ID panel reveals compound heterozygous GNB5 variants in a novel patient. Front Genet. 2018;9:626.

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