Atypical benign partial epilepsy and a new variant of SLC35A3 gene plus 2p25.1 duplication. 2 Phenotypic-Genotypic correlation?

25 Atypical Benign Partial Epilepsy (ABPE), recognized also as pseudo-Lennox syndrome, is an 27 uncommon form of epilepsy characterized by generalized minor seizures such as atonic, absences, or 28 myoclonic seizures, and electroencephalographic pattern of focal or multifocal sharp waves with 29 activation of epileptiform discharges during sleep. ABPE is indicated as a variant of ESES (ILAE 30 classification 2017). ESES is a clinical entity that is characterized by encephalopathy with cognitive/ 31 behavioral regression and EEG pattern of electrical status epilepticus during slow sleep. Fine and 32 gross motor, language and social/behavioral impairment are associated symptoms, which may have 33 reversible or persistent course. ABPE has been ascribed to the group of the “epilepsy aphasia 34 spectrum” disorders, which includes also Rolandic Epilepsy, Landau-Kleffner syndrome, and 35 electrical status epilepticus during sleep/continuous spike-wave during sleep. We report a young boy 36 with a previous mild motor and language delay, who at 2-year-old presented with recurrent atonic 37 seizures and an EEG pattern consisting of continuous spike and waves during sleep. 38

Data generated by a genomic approach disclose a more comprehensive view of the genotype-49 phenotype correlation analysis for the novel pathogenic variant and ABPE. The relationship between 50 the phenotypic manifestations of the child and genetic data is discussed.

52
Background 53 Clinical aspect of atypical benign partial epilepsy (ABPE) was first described by Aicardi and Chevrie 54 [1] in seven children who showed benign clinical course not compatible at the differential diagnosis 55 with those recognized to be more severe and more complex as reported in patients with myoclonic-56 astatic epilepsy (MAE) [2]. In the report of Aicardi and Chevrie [1], the children showed several 57 types of seizures mainly partial motor, atypical absence, and myo-atonic seizures with onset of 58 symptoms between the ages of 2 years and 5 months to six years. In these children, aside from the 59 epileptic seizures, neither cerebral anomalies nor neurologic dysfunctions including developmental 60 delay/intellectual disability (DD/ID) were reported. To note, the EEG showed a striking contrast 61 between the registration carried in the awake presenting with focal paroxysms and the record during "ESES/CSWS", and in Landau-Kleffner syndrome (LKS), also called as acquired aphasia syndrome. 75 The inclusion of LKS in the ESES group has been recently suggested [15]. 76 We report a 7-year-old boy who showed a previous mild DD in motor and language domain. He 77 displayed at the age of 2 years recurrent atonic seizures with ESES recording. An atonic seizure was 78 registered during the Video-EEG recording. We have followed serially up the child with clinical 79 examination and EEG record reporting a constant, progressive improvement as regard both motor

88
A 2-year-old boy was first referred to the University-Hospital "Policlinico-Vittorio Emanuele", in 89 Catania (Italy) for consultation due to recurrent seizures. He is the first born of healthy unrelated 90 parents. The family history is negative for neurologic disorders. At the conception, the mother was 91 32 and the father 34 years old. The mother denied having infectious diseases during her pregnancy or 92 to have used drugs or alcohol. Fetal ultrasound examination was normal, as well as fetal movements.

93
The boy was born at 42 weeks of gestation after a normal pregnancy and normal delivery. At the 94 birth, his weight was 3.6 Kg, height 50 cm, and head circumference 35 cm (all within normal range).

95
The development steps were slightly delayed in motor (delay in walking) and in language (first word 96 at the age of 16 months). Sphincter control was reached at a normal age. At the age of 24 months, the 97 child presented critical events consisting of sudden and rapid loss of muscle tone, ahead or behind, 98 or laterally mainly in the right side, of short duration (a few seconds) apparently without loss of 99 consciousness with a high frequency (20-30 episodes per day), preceded by pre-ictal warning signs.  Initial treatment with sodium valproate (20 mg/kg/day) was subsequently increased to 30 mg/kg/day 117 with partial control of the seizures, but a subsequent EEG 6 months later was unchanged. A negative 118 myoclonus seizure with loss of head control was registered on the video-EEG, which showed spike 119 discharges and slow waves prevalent in the fronto-centro-temporal areas (Figure 2). At the age of 3 120 years, ethosuximide (20 mg/kg/day) as an add-on was introduced. This treatment reduced the 121 frequency of seizures, but these continued to be present at a frequency of five episodes per day. In 122 this phase, the EEG anomalies were less evident. At the age of 4 years, valproate was reduced to with the other children, with sufficient scholastic performance and IQ measured 70 at the WISC scale.

128
Hair was present in the limbs and trunk but were less abundant than before. An EEG recorded during 129 sleep showed the presence of spikes in the fronto-central areas (Figure 3). At the most recent  The EE panel included 23 genes:

165
The aCGH analysis revealed a partial duplication (425 kb) of chromosome 2p25.1 with the following We report on a child affected previously by mild motor and language delay, who at the age of 2 years 179 presented with recurrent atonic seizures and a typical EEG pattern of spikes and waves occurring in 180 more than 85% of the sleep recording.

181
The first seizures were observed at the age of 2 years with recurrent episodes of loss of muscle tone

203
The duration of typical EEG anomalies ranged from 6 to 52 months in 91% of the cases, and in 53% 204 of the cases, borderline or moderate cognitive impairment was noted. In a report by van    We confirm that we have read the Journal's position on issues involved in ethical publication and 298 affirm that this report is consistent with those guidelines.  Availability of data and materials 305 The dataset supporting the conclusions of this article is included within the article (and its additional 306 files.

307
Competing interests 308 The authors declare that they have no competing interests.

310
The authors did not receive any funding in the preparation of the manuscript.