Atypical absence seizures are generalized non-convulsive seizures that often occur in children with cognitive impairment. They are common in refractory epilepsy and have been recognized as one of the hallmarks of developmental epileptic encephalopathies. Notably, pathogenic variants associated with AAS, such as GABRG2, GABRG3, SLC6A1, CACNB4, SCN8A, and SYNGAP1, are also linked to developmental epileptic encephalopathies. Atypical absences differ from typical absences in that they are frequently drug-resistant and the prognosis is dependent on the etiology or related epileptic syndromes. To improve clinicians\' understanding of atypical absences and provide novel perspectives for clinical treatment, we have reviewed the electro-clinical characteristics, etiologies, treatment, and prognosis of atypical absences, with a focus on the etiology of advancements in gene variants, shedding light on potential avenues for improved clinical management.

OBJECTIVE: To summarize the clinical phenotype and genetic characteristics of children with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations.
METHODS: A retrospective analysis was performed on the medical data of 8 children with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations who were diagnosed and treated in the Department of Pediatrics, Xiangya Hospital of Central South University.
RESULTS: The mean age of onset was 9 months for the 8 children. All children had moderate-to-severe developmental delay (especially delayed language development), among whom 7 children also had seizures. Among these 8 children, 7 had novel heterozygous mutations (3 with frameshift mutations, 2 with nonsense mutations, and 2 with missense mutations) and 1 had 6p21.3 microdeletion. According to the literature review, there were 48 Chinese children with mental retardation caused by SYNGAP1 gene mutations (including the children in this study), among whom 40 had seizures, and the mean age of onset of seizures was 31.4 months. Frameshift mutations (15/48, 31%) and nonsense mutations (19/48, 40%) were relatively common in these children. In terms of treatment, among the 33 children with a history of epileptic medication, 28 (28/33, 85%) showed response to valproic acid antiepileptic treatment and 16 (16/33, 48%) achieved complete seizure control after valproic acid monotherapy or combined therapy.
CONCLUSIONS: Children with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations tend to have an early age of onset, and most of them are accompanied by seizures. These children mainly have frameshift and nonsense mutations. Valproic acid is effective for the treatment of seizures in most children.
目的: 总结SYNGAP1基因相关常染色体显性智力障碍5型患儿临床表型及遗传学特点。方法: 回顾性分析中南大学湘雅医院儿科诊治的8例SYNGAP1基因相关智力障碍患儿的临床资料。结果: 8例患儿的平均起病年龄为9月龄，均伴有中重度发育迟缓（语言落后为著），其中7例患儿伴癫痫发作。8例患儿中7例为新发杂合变异（3例移码变异、2例无义变异和2例错义变异），1例为6p21.3微缺失。目前已报道的中国SYNGAP1基因变异相关智力障碍患儿（包括该研究）有48例，其中40例伴癫痫发作，癫痫发作平均起病年龄为31.4月龄，多为移码变异（15/48，31%）和无义变异（19/48，40%）。治疗上，有癫痫用药史记录的33例患儿中，丙戊酸抗癫痫发作治疗对多数患儿有效（85%，28/33），其中48%（16/33）患儿丙戊酸单药或联合用药治疗达到发作完全控制。结论: SYNGAP1基因相关常染色体显性智力障碍5型患儿起病年龄早，多数患儿伴癫痫发作，以移码变异和无义变异为主，丙戊酸抗癫痫发作治疗对多数患儿有效。.

Neurodevelopmental disorders (NDDs) are a heterogeneous group of conditions including intellectual disability, global developmental delay, autism spectrum disorder, and attention deficit hyperactivity disorder. Advances in genetic diagnostic technology have led to the identification of a number of NDD-associated genes, but reports of cognitive and developmental outcomes in affected individuals have been variable. The objective of this scoping review is to synthesize available information pertaining to the developmental outcomes of individuals with pathogenic variants in ten emerging recurrent NDD-associated genes identified from large scale sequencing studies; ADNP, ANKRD11, ARID1B, CHD2, CHD8, CTNNB1, DDX3X, DYRK1A, SCN2A, and SYNGAP1. After a comprehensive search, 260 articles were selected that reported on neurodevelopmental measures or diagnoses. We identify the spectrum of developmental outcomes for each genetic NDD, including prevalence of intellectual disability, frequency of co-morbid NDDs such as ADHD and autism, and commonly reported medical issues that can help inform diagnosis and treatment. There are significant gaps in our understanding of the natural history of these conditions. Future research focusing on barriers to assessment, the development of modified assessment tools appropriate for long-term outcomes in genetic NDD, and collection of longitudinal data will increase understanding of prognosis in these conditions and inform evaluations of treatment.

OBJECTIVE: Heterozygous SYNGAP1 gene mutations have been associated with several forms of idiopathic generalized epilepsy, autism spectrum disorders and delay of psychomotor development. We report eight patients with a SYNGAP1 mutation and chewing/eating induced reflex seizures as new phenotype and compare them to other patients with eating epilepsy and genetic mutations.
METHODS: Presentation of clinical and anamnestic features and retrospective analysis of Video-EEG data of a 4 year old index patient with SYNGAP1 mutation and chewing /eating induced seizures. Clinical and anamnestic features and home videos of seven additional patients (4 female; age: 4-14 years) with SYNGAP1 mutation and eating induced reflex seizures were compared.
RESULTS: All reflex seizures of the index patient showed similar focal EEG pattern with 1-5 seconds high amplitude, irregular 3/sec spike-wave complexes with initiation from left temporo-occipital, right temporo-occipital or bi- occipital / temporo-occipital regions. Eyelid myoclonia, the most common seizure type in all 8 patients, were typically initiated by eating or other simple orofacial stimuli. In the index patient eye closure preceded eating induced-eyelid myoclonia in 30/38 seizures.
CONCLUSIONS: The main clinical features of our patient (i.e. intellectual disability, epilepsy, autistic features) are compatible with previous reports on patients with SYNGAP1 mutations. This is the first complete description of eating induced seizures in association with SYNGAP1 mutations. Whether eye closure sensitivity (ECS) represents an independent reflex epileptic trait, as seen in other patients with idiopathic \"generalized\" epilepsies (IGE), or eye closure is part of a complex trigger mechanism in SYNGAP1 patients\' remains to be elucidated.

OBJECTIVE: To develop hypotheses regarding the relationship between Sturge-Weber syndrome (SWS) and other abnormalities in a subset of patients.
METHODS: We retrospectively reviewed medical records in a group of 28 patients with SWS, noting the main features of SWS and accompanying unexpected abnormalities. We also conducted a literature review of abnormalities associated with SWS.
RESULTS: Twenty-eight medical records of patients with SWS were reviewed. Of this number, we found 8 (29%, 2 female) patients who manifested other abnormalities. Our review of the literature uncovered 15 additional cases with associated abnormalities.
CONCLUSIONS: We hypothesize that the abnormalities associated with SWS suggest testable insights regarding pathogenesis and that chromosome 17p1-p13 may be a candidate region for genes involved with SWS. We also propose that some patients with SWS may have disorders of cholesterol biosynthesis or carbohydrate glycosylation.

Apart from their lipid lowering activity, HMG-CoA reductase inhibitors (statins) impair numerous cellular functions associated with metastasis, e.g. gene expression, angiogenesis, cell adhesion, cell motility and invasiveness. Furthermore, statins have impact on apoptotic cell death and modulate cellular susceptibility to cell killing by anticancer drugs and ionizing radiation. Part of the effects provoked by statins are due to the inhibition of the prenylation of low molecular weight GTPases, in particular Ras and Rho, which play key roles in signaling evoked by stimulation of cell surface receptors. C-terminal lipid modification of Ras/Rho GTPases is essential for their correct intracellular localization and function. By depletion of the cellular pool of isoprene precursor molecules, statins reduce the level of membrane-bound active Ras/Rho proteins, thereby impairing corresponding functions. Since broad clinical experience already exists for statins, their incorporation into established tumor-therapeutic regimens would be realizable in a rather short period of time. Here, data available at present arguing for the usefulness of statins in anticancer therapy are summarized and discussed.

A dynamic equilibrium or is responsible for the proper function of a living organism. Physiological events regulating proliferation, apoptosis, differentiation, and cell arrest, modulates the correct homeostasis and functionality of all tissues. Cancer is a consequence of a disorder in these sequential events, which results in the alteration of the ratio between cell death, cell differentiation and cell proliferation that ultimately leads to an increase in the number of dysregulated cells. Most of the processes which control the are regulated by signalling pathways, whose components are currently being explored as potential targets for the design of antitumoral drugs. Many in vivo studies have shown that Ras and Rho proteins are key modulators of mitogenic signalling, and are involved in the carcinogenesis of several human tumors. The development of recent drugs that elicit antitumoral activity by blocking some of the Ras and/or Rho effects, is discussed in this review.

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