Abstract
[Spurgeon AL, Keaveney SF, Ng YT. Refractory Jeavons Syndrome from Birth Symptomatic to PLCB1 Mutation. Child Neurol Open. 2023 Jul 2;10:2329048X231183524. doi: 10.1177/2329048X231183524. PMID: 37441061; PMCID: PMC10334019.]
The authors have requested corrections to the article in response to reader concerns.
A reader raised concerns about the paper which were addressed by the authors.
1. The first concern was in regard to the following statement on page 1: “EEM was recently recognized as its own diagnosis by the International League Against Epilepsy (ILAE) in 2017 as ‘absences with palpebral myoclonus’ and the ILAE neurophysiology task force classified it as a generalized epileptic syndrome with its own clinical and EEG characteristics.4”.
The reader’s concern was that the 2017 seizure classification position paper by Fisher et. al. did recognize absence with eyelid myoclonia as a new seizure type, but that this differs from recognizing EEM as an epilepsy syndrome. They suggested that this was only done in the 2022 ILAE definition of epilepsy syndromes with onset in childhood (Specchio et al). There were concerns that the primary documents should have been cited, rather than the review paper [4] cited in the article. The authors acknowledge the concerns regarding referencing the review article (de la Jara et al., 2021) as opposed to the primary papers (Fisher et al. 2017 and Scheffer et al. 2017) and apologize for doing so. The authors recognize that citing the review article may have led to discrepancies in official classifications regarding seizure types versus syndromes. The authors made the necessary changes to the section by using the primary sources recommended and the statement should be amended to read:
“In 2017, the International League Against Epilepsy (ILAE) neurophysiology task force utilized EEG to aid in diagnosis and classification of epilepsy syndromes and placed ‘eyelid myoclonia with or without absences or Jeavons syndrome’ within either the genetic generalized or idiopathic generalized epilepsy spectrum while still acknowledging that it has its own clinical and EEG characteristics.7 Also in 2017, the ILAE Commission for Classification and Terminology classified ‘absence with eyelid myoclonia’ as a new generalized seizure type relative to the previous 1981 classification system.4 Demographically, this syndrome is twice as common in females and accounts for 7.3-12.9% of generalized epilepsies and 2.5% to 2.7% of epilepsies overall. The diagnosis is delayed an average of 9.6 years, and the average time of diagnosis is approximately 7 years.9,15”
7. Koutroumanidis M, Arzimanoglou A, Caraballo R, et al. The role of EEG in the diagnosis and classification of the epilepsy syndromes: a tool for clinical practice by the ILAE Neurophysiology Task Force (Part 1). Epileptic Disorders. 2017;19(3):233-298. doi:10.1684/epd.2017.0935
4. Fisher RS, Cross JH, French JA, et al. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):522-530. doi:10.1111/epi.13670
9. de la Jara J, Vásquez-Hernández C, Ramírez-Rojo E, Moya-Vilches J. Uncommon epileptic syndromes in children: a review. Seizure. 2021;90:17-27. doi:10.1016/j.seizure.2021.05.005
15. Smith KM, Youssef PE, Wirrell EC, et al. Jeavons Syndrome: Clinical Features and Response to Treatment. Pediatr Neurol. 2018;86:46-51. doi:10.1016/j.pediatrneurol.2018.06.001
2. The second concern was in reference to the following section on page 2: “Patient's genetic panel came back with a heterozygous PLCB1 mutation reported as likely pathogenic. She was also heterozygous for SCN1A and SCN9A mutations. Her father's genetic panel was also heterozygous for SCN1A and SCN9A mutations although he has no history of seizures.” The reader was concerned with the use of the term ‘mutation’ instead of using the term ‘genetic variants’ instead. They also suggest that there should be details given regarding the variants. The authors appreciate the suggestion to use different terminology regarding genetic variants versus mutations, recognizing that not all variants are necessarily pathologically relevant mutations. The authors addressed this by changing the terminology used from ‘mutation’ to ‘genetic variants’ and ‘variation.’
The section should be amended to read:
“Patient’s genetic panel came back with a heterozygous PLCB1 mutation reported as likely pathogenic. She was also heterozygous for genetic variants of SCN1A and SCN9A. Her father’s genetic panel was also heterozygous for the same variations in SCN1A and SCN9A seen in the patient’s genetic panel, although he has no history of seizures. Her mother’s genetic testing came back normal.”
3. The third concern was in regard to the following statement on page 3: ‘Similarly, in infants found to have haploinsuffiency of PLCB1, the most common presentation was early-onset seizures as well as profound intellectual disability, hypotonia, hyperreflexia, and microcephaly.10’ The reader suggested that in the referenced paper by Coppola et al. (2019) the patient had a homozygous deletion affecting PLCB1. The third point highlighted an error in the information drawn from Coppola et al. (2019) and that error has been corrected.
The sentence should be amended to read:
“Similarly, in infants found to have homozygous deletion of PLCB1, the most common presentation was early-onset seizures as well as profound intellectual disability, hypotonia, hyperreflexia, and microcephaly.1”
1. Coppola A, Cellini E, Stamberger H, et al. Diagnostic implications of genetic copy number variation in epilepsy plus. Epilepsia. 2019;60(4):689- 706. doi:10.1111/epi.14683
4. The last point made by the reader was regarding a sentence on page 3: ‘Of note, many of the infants featured in these studies were homozygous for a mutation of PLCB1, but one study included a child noted to have a heterozygous deletion in the promoter region and exons 1-3, resulting in a similar phenotype of early-onset seizures and developmental delay.9’ The reader suggested that in the Schoonjans et al. (2016) paper cited, the patient had a homozygous deletion affecting PLCB1. It appears there was a discrepancy of citations as opposed to an informational error. The authors had cited information from a table that was referencing another source, and the appropriate primary source has now been cited to alleviate any more confusion.
The sentence remains the same but the should be amended to cite the following reference:
12. Ngoh A, McTague A, Wentzensen IM, et al. Severe infantile epileptic encephalopathy due to mutations in PLCB1: expansion of the genotypic and phenotypic disease spectrum. Dev Med Child Neurol. 2014;56(11):1124-1128. doi:10.1111/dmcn.12450