Genomic Balancing Act: Deciphering DNA rearrangements in the Complex Chromosomal Aberration involving 5p15.2, 2q31.1 and 18q21.32.

Despite extensive research into the genetic underpinnings of neurodevelopmental disorders (NDD), many clinical cases remain unresolved. We studied a female proband with a NDD, mildly dysmorphic facial features, and brain stem hypoplasia on neuroimaging. Comprehensive genomic analyses revealed a terminal 5p loss and terminal 18q gain in the proband while a diploid copy number for chromosomes 5 and 18 in both parents. Genomic investigations in the proband identified an unbalanced translocation t(5;18) with additional genetic material from chromosome 2 (2q31.3) inserted at the breakpoint, pointing to a complex chromosomal rearrangement (CCR) involving 5p15.2, 2q31.3, and 18q21.32. Breakpoint junction analyses enabled by long read genome sequencing unveiled the presence of four distinct junctions in the father, who is carrier of a balanced CCR. The proband inherited from the father both the abnormal chromosome 5 resulting in segmental aneusomies of chr5 (loss) and chr18 (gain) and a der(2) homologue. Evidences suggest a chromoplexy mechanism for this CCR derivation, involving double-strand breaks (DSBs) repaired by non-homologous end joining (NHEJ) or alternative end joining (alt-EJ). The complexity of the CCR and the segregation of homologues elucidate the genetic model for this family. This study demonstrates the importance of combining multiple genomic technologies to uncover genetic causes of complex neurodevelopmental syndrome and to better understand genetic disease mechanisms.

Ketogenic diet in childhood epilepsy: clinical algorithm in a tertiary care center.

Background: Dietary therapies play a crucial role in managing patients, especially those who have specific types of epilepsy, display adverse effects, or are not responding to pharmacological treatments. The ketogenic diet (KD) is a high-fat, restricted carbohydrate, and adequate protein regimen. The KD has proven to be an effective nonpharmacological treatment for drug-resistant epilepsy (DRE) by generating ketones that act as an alternative fuel source for the brain, thereby reducing the occurrence of seizures. The advantages of KD have been attributed to its universal availability, numerous administration techniques, and affordability. Objective: This article presents the KD algorithm developed by a multidisciplinary team of experts at the Children's Hospital, Ain Shams University, Egypt. The algorithm serves as a guide for implementing the KD in the treatment of DRE in children. The algorithm has been previously validated through a study. Methods: The algorithm consists of seven essential stages: (1) referral of patients to the Complex Epilepsy Committee, (2) pre-diet assessment of patients, (3) referral of patients to the Clinical Nutrition (CN) team, (4) diet selection and initiation, (5) seizure follow-up and diet fine-tuning, (6) diet reassessment after 3 months, and (7) evaluation of the KD journey after 24 months. Results: The KD algorithm was systematically developed and proved highly influential in facilitating the implementation of the KD. The algorithm yielded significant health benefits in pediatric patients. Conclusion: The KD algorithm provides a systematic approach to implementing the ketogenic diet and has demonstrated positive health outcomes in pediatric patients.

Ketogenic diet for epilepsy control and enhancement in adaptive behavior.

The Ketogenic Diet (KD) is gaining attention as a management line in childhood drug resistant epilepsy (DRE). The objective of this study was to highlight KD benefits for Ain Shams University (ASU) Children's Hospital patients. This cross-sectional study included all patients at the Ketoclinic of ASU Children's Hospital since it started. Anthropometric measurements and laboratory data were recorded. Chalfont severity score and daily frequency of epileptic attacks were used to evaluate KD efficacy. Vineland test was used to demonstrate the adaptive behavior of a selected group of patients. ASU Children's Hospital Ketoclinic records included 143 patients. During KD therapy, the weight and height/length assessment showed significant increase with significant decrease in the severity of seizures and its frequency. There were no significant changes in the lipid profile of the patients. Vineland test showed significant improvement in the adaptive behavior in 65% of patients. The Ketoclinic data proves that KD is a tolerable, safe, and effective line of therapy for DRE in children without significant negative impact on their anthropometric measurements or lipid profile. Furthermore, the enhancement in adaptive behavior is a promising finding. It is prudent to recommend wider scale studies for longer duration to demonstrate additional cognitive benefits of KD in pediatric age group.

Selenium and antioxidant levels in children with intractable epilepsy receiving ketogenic diet.

Ketogenic diet is a high-fat, low-carbohydrate, and adequate-protein diet. It is well-established as a treatment option for drug-resistant childhood epilepsies. Our study aimed to evaluate Selenium levels and oxidative stress in children receiving ketogenic diet for intractable seizures for 6 months. This is a comparative case-control study included 90 children under 6 years age. They were subdivided into three groups. Group I: Thirty patients with drug-resistant epilepsy under antiepileptic drugs only. Group II: Thirty patients with drug-resistant epilepsy under treatment with ketogenic diet for 6 months and antiepileptic drugs. Group III: Thirty age and sex-matched healthy children as controls. Full history taking with special emphasis on severity and frequency of seizures, neurological examination, anthropometric measurements and laboratory analysis for serum Malonaldehyde, and total antioxidant capacity and Selenium were done for all participants. The frequency and severity of seizures were significantly lower in group II receiving ketogenic diet than group I on antiepileptic drugs only. Selenium levels were significantly lower in epileptic patients in comparison to controls. However, it was markedly lower in the ketogenic diet group. Malonaldehyde levels were significantly higher in epileptic children in comparison to controls, with lower values among ketogenic diet group when compared to patients on antiepileptic drugs only. Total antioxidant capacity levels were significantly lower in epileptic patients in comparison to controls, with higher values among ketogenic diet group as compared to epileptic patients on pharmacological treatment. Ketogenic diet is an effective treatment for refractory epilepsy for its anti-epileptic mechanism. It also may exert antioxidant effects. The nutrient content of the ketogenic diet may not meet the recommended daily allowance for selenium. So, this should be taken into consideration for supplementation of minerals in adequate amounts for patients receiving this diet.

Childhood acute disseminated encephalomyelitis: an Egyptian pilot study.

Describing the variable clinical features, laboratory findings, neuroimaging findings, and treatments given to children who presented with ADEM and following them up both clinically and radiologically. 21 patients were recruited: 14 new cases, and 7 old ones presenting over the preceding 5 years (retrospective review of existing data). 11 males and 10 females, with a mean age of 4.4 years ± 2.7 SD, were included. All new patients were subject to full history, examination and a panel of investigations including MRI of the brain. Treatment was given in the form of pulsed methyl prednisolone or intravenous immunoglobulin (IVIG), followed by clinical and radiological follow-up every 3 months as needed. 11 cases occurred in spring, 8 post vaccine, of which 5 were after oral polio vaccine (OPV). MRI was done for all 21 patients and was abnormal in all of them, CT was done in only 10 patients as was normal in 9. Hyponatremia was seen in 11 patients. All patients who received corticosteroids showed prompt improvement. 6 out of 10 patients who received IVIG first failed treatment. Of the 17 treated patients, 10 had no sequelae and 10 had total lesion resolution on MRI at 3 months, versus 1 and 0 patients, respectively, in the untreated group. We found a disproportionately large number of post vaccination cases, especially after OPV. The association of ADEM with hyponatremia needs further study. MRI is central to diagnosis. Outcome is much better with treatment with steroids being far superior to IVIG. Excess use of IVIG should be discouraged.

Ketogenic diet versus gluten free casein free diet in autistic children: a case-control study.

Many diet regimens were studied for patients with autism spectrum disorder (ASD) over the past few years. Ketogenic diet is gaining attention due to its proven effect on neurological conditions like epilepsy in children. Forty-five children aged 3-8 years diagnosed with ASD based on DSM-5 criteria were enrolled in this study. Patients were equally divided into 3 groups, first group received ketogenic diet as modified Atkins diet (MAD), second group received gluten free casein free (GFCF) diet and the third group received balanced nutrition and served as a control group. All patients were assessed in terms of neurological examination, anthropometric measures, as well as Childhood Autism Rating Scale (CARS), Autism Treatment Evaluation Test (ATEC) scales before and 6 months after starting diet. Both diet groups showed significant improvement in ATEC and CARS scores in comparison to control group, yet ketogenic scored better results in cognition and sociability compared to GFCF diet group. Depending on the parameters measured in our study, modified Atkins diet and gluten free casein free diet regimens may safely improve autistic manifestations and could be recommended for children with ASD. At this stage, this study is a single center study with a small number of patients and a great deal of additional wide-scale prospective studies are however needed to confirm these results. TRIAL REGISTRATION NUMBER: UMIN-CTR Study Design: trial Number UMIN000021433.

Cardiac autonomic balance in children with epilepsy: value of antiepileptic drugs.

BACKGROUND: Dysfunction of the autonomous nervous system causes arrhythmias and, although previous studies have investigated the effects of epilepsy on the autonomic control of the heart, there is still uncertainty about whether imbalance of sympathetic, vagal, or both systems occurs in epilepsy as well as the effect of anticonvulsants on the autonomic system. AIM: To evaluate cardiac autonomic status in children with epilepsy on antiepileptic drugs. PATIENTS AND METHODS: Sixty patients with epilepsy were recruited from the Outpatient Neurology Clinic at Ain Shams University and were divided into the following groups: group I, drug naive; and group II, patients with epilepsy on regular antiepileptic drugs. The second group was further subdivided into the following groups: group IIa, received monotherapy; and group IIb, received polytherapy. Forty age- and sex-matched healthy children served as controls. Included patients underwent videorecorded electroencephalograph, Holter electrocardiogram (EKG) for time and frequency domains of heart rate variability, and standard EKG recording for QTc, QTd. RESULTS: Mean values of all time domain, total power, and high-frequency power were significantly lower, whereas low-frequency and low-frequency/high-frequency power, QTc. and QTd were significantly higher in group I compared with group II and in patients compared with controls. No significant difference was found between patients on different antiepileptic drug regimens regarding heart rate variability values. A significant negative correlation was found between Chalfont severity score and 50% of difference between adjacent, normal RR intervals in patient groups. CONCLUSIONS: Children with epilepsy have cardiac autonomic dysfunction evident in their heart rate variability assessment. Patients on antiepileptic drugs had better autonomic balance than those not on antiepileptic drugs. Holter and EKG follow-up should be considered for early detection in those at high-risk cardiac complications.

Transfusion transmitted hepatitis: where do we stand now? A one center study in upper egypt.

BACKGROUND: Despite progress made in the prevention of transfusion-transmitted infections (TTI) over the last few years, they continue to be a problem in many parts of the world, particularly in multitransfused patients. OBJECTIVES: The aim of this study was to estimate the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), and to evaluate the screening and vaccination program among our cohort of multitransfused children from Qena, Upper Egypt. PATIENTS AND METHODS: One-hundred children suffering from diseases requiring repeated blood transfusions were included in the study. They were classified into group 1, which included 67 children with thalassemia, and group 2, which included 33 children with hemophilia. Screening for hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody and antibody to HCV was done using a second-generation enzyme-linked immunosorbent assay technique. RESULTS: Only 12% of all patients were either acutely or chronically infected with HBV. 46% were immune due to previous vaccination, whereas 39% of patients were not protected from HBV infection. HCV antibodies were positive in 45% of cases. Seventy-eight patients had a complete hepatitis B vaccination in the form of three doses as documented by birth certificate. Thirty-six patients mentioned history suggestive of hepatitis. The prevalence of the studied hepatitis markers was similar in both the thalassemia and hemophilia groups of children. CONCLUSIONS: Transfusion-transmitted hepatitis is still a major problem for multitransfused children in Egypt. More effort is required to reduce the infection rate through proper screening of blood and blood products, strict emphasis on receiving the vaccine, regular follow-up for those children with a hepatitis B antibody titer, and providing booster doses for those in need.