The genetic profile of childhood neuromuscular disorders: A single center experience

Neuromuscular Diseases are a heterogeneous group of childhood disorders, and differential diagnosis can be challenging. Although there is no definitive treatment for the most of this group of diseases, early diagnosis is important with the development of new treatment methods. In this study, we aimed to draw attention to the importance of new generation genetic tests in diagnosing neuromuscular diseases. In this retrospective study, we reviewed the records of 800 patients with suspected neuromuscular diseases followed in the Neuromuscular Clinic of Marmara University Pendik Training and Research Hospital between December 2011 and January 2023 according to their demographic, clinical and genetic characteristics. Patients who were diagnosed with Duchenne muscular dystrophy and spinal muscular atrophy with targeted gene testing were excluded from the study. The results of targeted gene testing, clinical exome sequencing (CES), whole exome sequencing (WES) and mitochondrial genome analysis were analysed

Awareness of sudden unexpected death in epilepsy among parents of children with epilepsy in a tertiary center

Objective: Sudden unexpected death in epilepsy (SUDEP) is the second leading neurological cause of potential years of lifelost after stroke. Despite growing numbers of studies on social aspects of epilepsy, there is a paucity of research on the awareness of SUDEP among the parents of children with epilepsy (CWE), especially in Turkey. In this study, we aimed to evaluate the knowledge of parents of the CWE regarding SUDEP in the tertiary setting. Material and methods: A total of 146 parents (108 female) aged 19 to 55 years (median age:34) of CWE were included at Marmara University, School of Medicine, Department of Pediatric Neurology outpatient clinic between May 2018 and September 2018. A total of 30 multiple-choice questions and a written survey were administered, which consisted of three sections. In the first section, the sociodemographics of parents and CWE were questioned. In the second section, the severity of epilepsy was evaluated. In the third section, the knowledge level and awareness of parents of CWE were assessed. Results: Of 146 parents, only 16.6% previously heard about SUDEP, while 45% of them heard from their relatives. The presence of prior knowledge of SUDEP was associated with the presence of prolonged postictal confusion and longer duration of epilepsy (p < 0.05). Ninety-seven (66%) parents desired to be informed about SUDEP, while 76 (54.7%) of them agreed that this information should be given at the time of diagnosis. The degree of anxiety in parents regarding death of epilepsy-related causes was significantly related with prolonged postictal confusion (p < 0.001) and using three or more antiepileptic drugs (p = 0.005). Conclusion: Our data suggest that knowledge about SUDEP among parents with CWE found inadequate in Turkey. There should be much effort to inform parents and caregivers in epilepsy clinics on SUDEP, which may help to reduce the associated risk factors. (C) 2020 Elsevier Inc. All rights reserved

Comparison of classifications of seizures: A preliminary study with 28 participants and 48 seizures

Purpose: Our aim was to compare three available seizure classifications (SCs), namely, the international classification of epileptic seizures published in 1981 (ICES; Epilepsia 1981;22:489-50); the semiological seizure classification (SSC) by H. Lüders, J. Acharya, C. Baumgartner, et al. (Epilepsia 1998;39:1006-13; Acta Neurol Scand 1999;99:137-41); and the proposal of a new diagnostic scheme for seizures (PDSS) by J. Engel, Jr. (Epilepsia 2001;42:796-803) published in 2001. The three SCs were compared with respect to diagnostic success rates, usefulness, and consistency by a large group of neurologists in this preliminary study. Methods: After a training period, 28 blindfed participants with different levels of experience with epilepsy classified videos or written descriptions of 48 randomly selected seizures according to the three SCs. Definite diagnoses of the seizures were established based on all clinical, ictal/interictal EEG, and MRI data. All the participants answered a questionnaire concerning their preferences for SCs after the study. Results: The overall diagnostic success rates were 81.4% for ICES, 80.5% for PDSS, and 87.5%, for SSC. Various parameters concerning experience with epilepsy affected success rates positively, without reaching statistical significance, whereas experience with epilepsy surgery appeared to be a parameter significantly affecting the success rate in all SCs. In reliability analysis, Cronbach's α was 0.94 for ICES, 0.88 for PDSS, and 0.70 for SSC, all showing good agreement in the group. Nineteen reviewers chose SSC, eight chose ICES, and one chose PDSS as their preference in the questionnaire, completed after the end of the study. Conclusion: The results of this preliminary study demonstrate that with proper training, physicians treating epilepsy patients can handle new SCs, and emphasize the need for revision of the current classification. © 2005 Elsevier Inc. All rights reserved

Hemimegalencephaly and Hirschsprung's disease: a unique association

A 2-year-old boy with hemimegalencephaly and Hirschsprung's disease is reported. The unique association of these two entities is considered to be the presence of a common insult or insults that affect the innervation of the bowel and the formation of the cerebral cortex. Short-segment subtype of Hirschsprung's disease may suggest that this effect occurred between the eighth and twelfth weeks of gestation. Although there is a well-known coexistence of Hirschsprung's disease with the malformations that share a common neurocristopathic origin (abnormalities of neural crest cell growth, migration, or differentiation), a few extremely rare cases, as in this case, might reflect the coexistence of Hirschsprung's disease with a cerebral malformation (i.e., hemimegalencephaly) that is a nonneurocristopathic entity by itself

Demographic and Clinical Findings of Cerebral Palsy Patients in Istanbul: A Multicenter Study

Objective: The objective of this study is to identify epidemiological characteristics of patients with cerebral palsy (CP) in Istanbul, including demographic information, clinical types, risk factors, and some clinical features. Material and Methods: This is a retrospective and multicenter study, with the participation of 11 training and university hospitals in Istanbul. Demographic and clinical data of patients with CP presenting to university and training hospitals in Istanbul between 2005 and 2007 were recorded. Data were collected by the Istanbul Cerebral Palsy Study Group (ICPSG). Results: A total of 730 patients with a mean age of 7.27 +/- 4.63 (2-18 years) were enrolled into the study; 429 (58.8%) of the patients were male and 301 (41.2%) were female. During clinical typing, it was seen that 91% of the patients were spastic, 3.6% was mixed, 3.2% was dyskinetic, and 0.7% was ataxic. Also, 51.9 % of the patients had a diagnosis of CP during 0-6 months of age, 24.6% had the diagnosis during 6-12 months of age, and 23.5% in the twelfth month or later. Of the cases, 32% had speech disorders, 23.1% had mental retardation, and 20.9% had epilepsy. Conclusion: There are few studies about the demographic characteristics of patients with SP in our country. This study is a pilot study to determine the profile of cases of CP patients in our country and to create a CP patient pool for the future prospective studies

De novo FZR1 loss-of-function variants cause developmental and epileptic encephalopathies

FZR1, which encodes the Cdh1 subunit of the Anaphase Promoting Complex, plays an important role in neurodevelopment by regulating the cell cycle and by its multiple post-mitotic functions in neurons. In this study, evaluation of 250 unrelated patients with developmental and epileptic encephalopathies and a connection on GeneMatcher led to the identification of three de novo missense variants in FZR1. Whole-exome sequencing in 39 patient-parent trios and subsequent targeted sequencing in an additional cohort of 211 patients was performed to identify novel genes involved in developmental and epileptic encephalopathy. Functional studies in Drosophila were performed using three different mutant alleles of the Drosophila homolog of FZR1 fzr. All three individuals carrying de novo variants in FZR1 had childhood onset generalized epilepsy, intellectual disability, mild ataxia and normal head circumference. Two individuals were diagnosed with the developmental and epileptic encephalopathy subtype Myoclonic Atonic Epilepsy. We provide genetic-association testing using two independent statistical tests to support FZR1 association with developmental epileptic encephalopathies. Further, we provide functional evidence that the missense variants are loss-of-function alleles using Drosophila neurodevelopment assays. Using three fly mutant alleles of the Drosophila homolog fzr and overexpression studies, we show that patient variants can affect proper neurodevelopment. With the recent report of a patient with neonatal-onset with microcephaly who also carries a de novo FZR1 missense variant, our study consolidates the relationship between FZR1 and developmental epileptic encephalopathy, and expands the associated phenotype. We conclude that heterozygous loss-of-function of FZR1 leads to developmental epileptic encephalopathies associated with a spectrum of neonatal to childhood onset seizure types, developmental delay and mild ataxia. Microcephaly can be present but is not an essential feature of FZR1-encephalopathy. In summary, our approach of targeted sequencing using novel gene candidates and functional testing in Drosophila will help solve undiagnosed myoclonic atonic epilepsy or developmental epileptic encephalopathy cases

Characteristic and overlapping features of migraine and tension-type headache

Objective.-This epidemiological survey was conducted to investigate comprehensive characteristic and overlapping features of migraine and tension-type headache (TTH) disorders classified based on International Classification of Headache Disorders-II. Methods.-The stratified cohort of this study was composed of 2504 schoolchildren aged 10 to 17 years. A 38-item questionnaire inquiring all characteristic features of primary headache syndromes mandatory for classification was applied to selected 483 children with recurrent headache in the last 6 months. Results.-Migraine was diagnosed in 227 (47.0%) of 483 children and TTH in 154 (31.9%). Out of 125 children with definite migraine, 73 (58.4%) reported tension-type symptoms and 94 (68.1%) of 138 children with definite TTH reported migraine-type symptoms. Pressing pain (21%) and lack of aggravation of pain by physical activity (34%) were the major tension-type features in patients with migraine. Throbbing quality (43%) and aggravation by physical activity (30%) determined the main migraine-type features in patients with TTH. Conclusion.-The frequent co-occurrence of migraine and TTH symptoms suggests the presence of a common pathogenesis

Evaluation of vestibular functions in children with vertigo attacks

Aim: To examine vestibular system functions in children with episodic vertigo attacks. Methods: Thirty four children (20 males) aged 4-18 years with paroxysmal dizziness and/or vertigo attacks were evaluated. A medical history for vestibular symptoms and migraine was taken. Vestibular and auditory functions were assessed. Results: Chronic headache attacks consistent with migraine were reported in 12 children and motion sickness was reported in 30. Family history in first degree relatives was positive for migraine in 29 children and for episodic vertigo in 22. Electronystagmography and videonystagmography showed two types of nystagmus: spontaneous vestibular nystagmus (41%) and benign paroxysmal positional nystagmus (BPPN) (59%). The first type of nystagmus was assessed as a sign of vestibulopathy and the patients with BPPN were diagnosed as having benign paroxysmal positional vertigo (BPPV). Audiometric examination in four cases revealed bilateral sensory neural hearing loss in low frequencies. Pure tone averages in 30 cases were within normal ranges; however low frequencies in 28 of them were approximately 10 dB lower than high frequencies. Unilateral caloric responses diminished in eight children. Conclusions: Peripheral vestibular problems in childhood present in a wide spectrum, which varies from a short episode of dizziness to a typical vestibular attack with fluctuating sensory neural hearing loss or episodes of BPPV. A considerable number of these vestibular problems might be related to the migraine syndrome