TY - JOUR
T1 - PIGN encephalopathy: Characterizing the epileptology
AU - Bayat, A.
AU - Valles-Ibanez, G.
AU - Pendziwiat, M.
AU - Knaus, A.
AU - Alt, K.
AU - Biamino, E.
AU - Bley, A.
AU - Calvert, S.
AU - Carney, P.
AU - Caro-Llopis, A.
AU - Ceulemans, B.
AU - Cousin, J.
AU - Davis, S.
AU - Portes, V.
AU - Edery, P.
AU - England, E.
AU - Ferreira, C.
AU - Freeman, J.
AU - Gener, B.
AU - Gorce, M.
AU - Heron, D.
AU - Hildebrand, M.S.
AU - Jezela-Stanek, A.
AU - Jouk, P.S.
AU - Keren, B.
AU - Kloth, K.
AU - Kluger, G.
AU - Kuhn, M.
AU - Lemke, J.R.
AU - Li, H.
AU - Martinez, F.
AU - Maxton, C.
AU - Mefford, H.C.
AU - Merla, G.
AU - Mierzewska, H.
AU - Muir, A.
AU - Monfort, S.
AU - Nicolai, J.
AU - Norman, J.
AU - O'Grady, G.
AU - Oleksy, B.
AU - Orellana, C.
AU - Orec, L.E.
AU - Peinhardt, C.
AU - Pronicka, E.
AU - Rosello, M.
AU - Santos-Simarro, F.
AU - Schwaibold, E.M.C.
AU - Stegmann, A.P.A.
AU - Stumpel, C.T.
N1 - Funding Information:
We would like to thank the families for participating in this study. We gratefully acknowledge support from the Health Research Council of New Zealand, Cure Kids New Zealand, the Ted and Mollie Car Endowment Trust, the National Health and Medical Research Council of Australia, the Medical Research Future Fund, the Australian Epilepsy Research Fund, the Swiss National Science Foundation, and the National Institutes of Health/National Institute of Neurological Disorders and Stroke.
Publisher Copyright:
© 2022 International League Against Epilepsy.
PY - 2022/4
Y1 - 2022/4
N2 - Objective Epilepsy is common in patients with PIGN diseases due to biallelic variants; however, limited epilepsy phenotyping data have been reported. We describe the epileptology of PIGN encephalopathy. Methods We recruited patients with epilepsy due to biallelic PIGN variants and obtained clinical data regarding age at seizure onset/offset and semiology, development, medical history, examination, electroencephalogram, neuroimaging, and treatment. Seizure and epilepsy types were classified. Results Twenty six patients (13 female) from 26 families were identified, with mean age 7 years (range = 1 month to 21 years; three deceased). Abnormal development at seizure onset was present in 25 of 26. Developmental outcome was most frequently profound (14/26) or severe (11/26). Patients presented with focal motor (12/26), unknown onset motor (5/26), focal impaired awareness (1/26), absence (2/26), myoclonic (2/26), myoclonic-atonic (1/26), and generalized tonic-clonic (2/26) seizures. Twenty of 26 were classified as developmental and epileptic encephalopathy (DEE): 55% (11/20) focal DEE, 30% (6/20) generalized DEE, and 15% (3/20) combined DEE. Six had intellectual disability and epilepsy (ID+E): two generalized and four focal epilepsy. Mean age at seizure onset was 13 months (birth to 10 years), with a lower mean onset in DEE (7 months) compared with ID+E (33 months). Patients with DEE had drug-resistant epilepsy, compared to 4/6 ID+E patients, who were seizure-free. Hyperkinetic movement disorder occurred in 13 of 26 patients. Twenty-seven of 34 variants were novel. Variants were truncating (n = 7), intronic and predicted to affect splicing (n = 7), and missense or inframe indels (n = 20, of which 11 were predicted to affect splicing). Seven variants were recurrent, including p.Leu311Trp in 10 unrelated patients, nine with generalized seizures, accounting for nine of the 11 patients in this cohort with generalized seizures. Significance PIGN encephalopathy is a complex autosomal recessive disorder associated with a wide spectrum of epilepsy phenotypes, typically with substantial profound to severe developmental impairment.
AB - Objective Epilepsy is common in patients with PIGN diseases due to biallelic variants; however, limited epilepsy phenotyping data have been reported. We describe the epileptology of PIGN encephalopathy. Methods We recruited patients with epilepsy due to biallelic PIGN variants and obtained clinical data regarding age at seizure onset/offset and semiology, development, medical history, examination, electroencephalogram, neuroimaging, and treatment. Seizure and epilepsy types were classified. Results Twenty six patients (13 female) from 26 families were identified, with mean age 7 years (range = 1 month to 21 years; three deceased). Abnormal development at seizure onset was present in 25 of 26. Developmental outcome was most frequently profound (14/26) or severe (11/26). Patients presented with focal motor (12/26), unknown onset motor (5/26), focal impaired awareness (1/26), absence (2/26), myoclonic (2/26), myoclonic-atonic (1/26), and generalized tonic-clonic (2/26) seizures. Twenty of 26 were classified as developmental and epileptic encephalopathy (DEE): 55% (11/20) focal DEE, 30% (6/20) generalized DEE, and 15% (3/20) combined DEE. Six had intellectual disability and epilepsy (ID+E): two generalized and four focal epilepsy. Mean age at seizure onset was 13 months (birth to 10 years), with a lower mean onset in DEE (7 months) compared with ID+E (33 months). Patients with DEE had drug-resistant epilepsy, compared to 4/6 ID+E patients, who were seizure-free. Hyperkinetic movement disorder occurred in 13 of 26 patients. Twenty-seven of 34 variants were novel. Variants were truncating (n = 7), intronic and predicted to affect splicing (n = 7), and missense or inframe indels (n = 20, of which 11 were predicted to affect splicing). Seven variants were recurrent, including p.Leu311Trp in 10 unrelated patients, nine with generalized seizures, accounting for nine of the 11 patients in this cohort with generalized seizures. Significance PIGN encephalopathy is a complex autosomal recessive disorder associated with a wide spectrum of epilepsy phenotypes, typically with substantial profound to severe developmental impairment.
KW - congenital disorder of glycosylation
KW - developmental and epileptic encephalopathy
KW - epilepsy
KW - GPI-anchoring disorder
KW - intellectual disability
KW - HYPOTONIA-SEIZURES SYNDROME
KW - CONGENITAL-ANOMALIES
KW - PRENATAL-DIAGNOSIS
KW - MUTATION
KW - PHENOTYPE
KW - PROTEINS
KW - EPILEPSY
U2 - 10.1111/epi.17173
DO - 10.1111/epi.17173
M3 - Article
C2 - 35179230
SN - 0013-9580
VL - 63
SP - 974
EP - 991
JO - Epilepsia
JF - Epilepsia
IS - 4
ER -