Shared Biological Pathways and Processes in Patients with Intellectual Disability: A Multicenter Study.

BACKGROUND: Although the underlying genetic causes of intellectual disability (ID) continue to be rapidly identified, the biological pathways and processes that could be targets for a potential molecular therapy are not yet known. This study aimed to identify ID-related shared pathways and processes utilizing enrichment analyses. METHODS: In this multicenter study, causative genes of patients with ID were used as input for Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. RESULTS: Genetic test results of 720 patients from 27 centers were obtained. Patients with chromosomal deletion/duplication, non-ID genes, novel genes, and results with changes in more than one gene were excluded. A total of 558 patients with 341 different causative genes were included in the study. Pathway-based enrichment analysis of the ID-related genes via ClusterProfiler revealed 18 shared pathways, with lysine degradation and nicotine addiction being the most common. The most common of the 25 overrepresented DO terms was ID. The most frequently overrepresented GO biological process, cellular component, and molecular function terms were regulation of membrane potential, ion channel complex, and voltage-gated ion channel activity/voltage-gated channel activity, respectively. CONCLUSION: Lysine degradation, nicotine addiction, and thyroid hormone signaling pathways are well-suited to be research areas for the discovery of new targeted therapies in ID patients.

Effects of levetiracetam treatment on autonomic nervous system functions in pediatric epilepsy patients.

BACKGROUND: This study investigated the effects of levetiracetam (LEV) treatment on cardiac rhythm and heart rate variability. METHODS: The study included two groups of patients diagnosed with non-lesional epilepsy who had not yet been treated and who presented to the outpatient pediatric neurology clinic at Van Training and Research Hospital, Van, Turkey, between 2019 and 2020. The heart rate variability (HRV) of 47 patients in the first group, before and at the 3rd month of treatment, and intravenous (IV) LEV loading in 13 patients in the second group was evaluated by Holter electrocardiography (ECG). RESULTS: It was determined that the values of triangular index, standard deviation of the RR intervals over a 24-hour period (SDNN), standard deviation of all 5-minute mean RR intervals (SDANN), mean of standard deviations of all normal RR intervals (SDNNI), the percentage of RR intervals with >50-millisecond variation (PNN50), and the square root of mean squared differences of successive RR intervals (RMSSD). HRV of 47 patients under LEV treatment significantly increased in the 3rd month of treatment compared to baseline (p < 0.05). No difference was found in HRV between the intravenous loading and the control group (p > 0.05). CONCLUSIONS: Our study suggests that the sympathovagal balance before treatment in the patient group is in favor of the sympathetic nervous system and that the sympathovagal imbalance improves after treatment. Our results show that LEV monotherapy and loading have no negative effect on HRV and potential cardiac arrhythmia risk in children with epilepsy.

Evaluation of immunization status in patients with cerebral palsy: a multicenter CP-VACC study.

Children with chronic neurological diseases, including cerebral palsy (CP), are especially susceptible to vaccine-preventable infections and face an increased risk of severe respiratory infections and decompensation of their disease. This study aims to examine age-appropriate immunization status and related factors in the CP population of our country. This cross-sectional prospective multicentered survey study included 18 pediatric neurology clinics around Turkey, wherein outpatient children with CP were included in the study. Data on patient and CP characteristics, concomitant disorders, vaccination status included in the National Immunization Program (NIP), administration, and influenza vaccine recommendation were collected at a single visit. A total of 1194 patients were enrolled. Regarding immunization records, the most frequently administrated and schedule completed vaccines were BCG (90.8%), hepatitis B (88.9%), and oral poliovirus vaccine (88.5%). MMR was administered to 77.3%, and DTaP-IPV-HiB was administered to 60.5% of patients. For the pneumococcal vaccines, 54.1% of children received PCV in the scope of the NIP, and 15.2% of children were not fully vaccinated for their age. The influenza vaccine was administered only to 3.4% of the patients at any time and was never recommended to 1122 parents (93.9%). In the patients with severe (grades 4 and 5) motor dysfunction, the frequency of incomplete/none vaccination of hepatitis B, BCG, DTaP-IPV-HiB, OPV, and MMR was statistically more common than mild to moderate (grades 1-3) motor dysfunction (p = 0.003, p < 0.001, p < 0.001, p < 0.00, and p < 0.001, respectively). Physicians' influenza vaccine recommendation was higher in the severe motor dysfunction group, and the difference was statistically significant (p = 0.029).Conclusion: Children with CP had lower immunization rates and incomplete immunization programs. Clinicians must ensure children with CP receive the same preventative health measures as healthy children, including vaccines. What is Known: • Health authorities have defined chronic neurological diseases as high-risk conditions for influenza and pneumococcal infections, and they recommend vaccines against these infections. • Children with CP have a high risk of incomplete and delayed immunization, a significant concern given to their increased healthcare needs and vulnerability to infectious diseases. What is New: • Influenza vaccination was recommended for patients hospitalized due to pneumonia at a higher rate, and patients were administered influenza vaccine more commonly. • Children with CP who had higher levels of motor dysfunction (levels 4 and 5) were more likely to be overdue immunizations.

Pyridoxine-dependent Epilepsy caused by a Novel homozygous mutation in PLPBP Gene.

Seizures in newborn infants may be the first finding of hereditary metabolic diseases. Pyridoxine-dependent epilepsy (PDE) is a treatable disorder associated with defects in the one of ALDH7A1, PNPO, or PLPBP genes and it is uncommon but progresses with persistent seizures in the neonatal and infancy period. The seizures are generally resistant to traditional antiepileptic drugs and show a dramatic response to high-dose pyridoxine. In 2016, mutations were reported in PLPBP (previously known as PROSC) gene, which encodes pyridoxal phosphate homeostatic protein (PLPHP).When early-onset antiepileptic resistant seizures are not treated, clinical findings emerge including the development of encephalopathy, congenital microcephaly, and subsequent retardation of psychomotor development. The present case is a 33-month-old female infant with seizures starting from postnatal day 1, who did not respond to traditional anti-epileptic drugs but responded to pyridoxine treatment. In the genetic tests, homozygote c.695 C > T (p.Ala232Val) mutation was determined in the PLPBP gene, which has not been previously identified. Since a specific treatment was found, this case is reported with the aim of emphasizing the need to consider pyridoxine dependence, which is one of the vitamin-dependent metabolic encephalopathies, in the differential diagnosis of epilepsy patients.

Evaluation of micronutrient levels in children with cerebral palsy.

BACKGROUND: Many studies evaluating the nutritional status of children with cerebral palsy (CP) have focused on energy requirements and protein intake. The present work aimed to assess nutritional status and micronutrient levels of children with (CP). METHODS: This multicenter, cross-sectional and observational study was conducted in 10 different cities in Turkey. Data were available for 398 participants. Anthropometric measurements, feeding mode, nutritional status, and micronutrient levels were evaluated. RESULTS: The study was conducted with 398 participants (303 patients and 95 healthy controls). Statistical analysis showed that according to the Gomez Classification, weight-for-age (WFA) revealed malnutrition in 92.6% of children with CP, based on Centers for Disease Control and Prevention percentiles. Measurements of micronutrient levels showed that zinc levels were low in patients, whereas vitamin A levels were low in controls. Phosphorous and manganese levels were significantly lower in malnourished children than in typical children. The results revealed that children consuming enteral nutrition solutions had higher selenium and lower zinc levels than non-consumers. CONCLUSIONS: Malnutrition is not only a protein- or calorie-based problem; micronutrient deficiencies might cause severe health problems. Children with chronic neurological disabilities must be carefully evaluated for these issues. Therefore, nutritional interventions should be adapted to nutrition.

Plasma bisphenol a and phthalate levels in children with cerebral palsy: a case-control study.

The case-control study aimed to evaluate potential sources of exposure and the plasma concentrations of bisphenol A (BPA) and phthalates in prepubertal children having cerebral palsy (CP) and healthy control. Blood samples of 68 CP and 70 controls were analyzed for BPA, di-(2-ethylhexyl)-phthalate (DEHP), mono-(2-ethylhexyl)-phthalate (MEHP), and dibutyl phthalate (DBP). BPA and DBP levels were similar in groups. The median DEHP and MEHP levels of the children with CP were significantly lower than those of the controls (p = 0.035, p < 0.001, respectively). Exposure to plastic food containers/bags, personal care hygiene products, household cleaners, wood/coal stove heating, and city water supplies were associated with increased odds of higher BPA and phthalate levels in children with CP. In conclusion, potential exposure sources for BPA and phthalates differ in children with CP and healthy controls, and children with CP are not exposed to higher levels of BPA and phthalates.

The neurodevelopmental profile of healthy children with premature anterior fontanel closure.

BACKGROUND: We aimed to assess the neurodevelopmental status of healthy children with premature anterior fontanel closure. METHODS: This retrospective observational study was conducted on 40 (20 M, 20 F) children admitted to Mersin University Pediatric Neurology Outpatient Clinic between 2015-2020 with complaints of premature fontanel closure. Patients with dysmorphic features, microcephaly, craniosynostosis, hypoxic-ischemic sequelae, infections, metabolic disorders, intracranial hemorrhage, epilepsy, endocrine problems, additional congenital anomalies, intrauterine growth retardation (IUGR), prematurity, and postmaturity were excluded. The Denver II and Bayley III tests were applied to all patients and controls. RESULTS: The Denver II identified retardations in gross motor skills (p = 0.015) and personal-social skills (p = 0.042) and Bayley III in cognitive (p = 0.030) and motor skills (p = 0.007) in the study group. None of the participants in the study group had neurodevelopmental retardation, according to the Bayley III normal standards. DISCUSSION: Our results suggest that children with premature fontanel closure may develop motor retardation. These children should, therefore, be closely monitored for neurodevelopmental aspects.

Neurodevelopmental risk evaluation of premature closure of the anterior fontanelle.

PURPOSE: To evaluate neurological development of completely healthy children with anterior fontanelle premature closure via Denver Developmental Screening Test II and to compare the results with control group. METHOD AND RESULTS: The records of 140 patients applied to Mersin University Pediatric Neurology Outpatient Clinic between 2011 and 2019 with the complaint of premature closure of the anterior fontanelle were retrospectively reviewed. Patients with microcephaly, craniosynostosis, infection, sequelae of hypoxia-ischemia, metabolic disorders, intracranial hemorrhage, epilepsy, endocrine problems, and dysmorphic features were excluded from the study. Sixty-six completely healthy children with anterior fontanelle premature closure were included in the study. Denver Developmental Screening Test II was performed by the same developmental specialist to the children with premature closure of the anterior fontanelle as well as to the healthy control group. For each child included in the case and the control group, 90% of the values for each development area were calculated and recorded. Then, the results were compared. Denver II Developmental Screening Test (p < 0.001) and gross motor subtest (p < 0.001) results showed statistically significant retardation in the case group compared with the control group. CONCLUSIONS: The study was the first study in the literature on the gross motor development of children with premature closure of anterior fontanelle, and it has been found significantly undeveloped compared with the control group, and it has been concluded that similar patients should be evaluated from this view point in pediatric neurology department.

Long-term cognitive outcomes of prematurely born infants: A longitudinal follow-up of Denver II, Bayley III and WISC-IV Tests.

BACKGROUND: Prematurity constitutes a risk factor for developmental delay in infancy and childhood. This study aims to: (i) determine long-term cognitive outcomes in prematurely delivered children and compare them with term-delivered children using the WISC-IV and Stroop tests; (ii) examine the relation between Denver II, Bayley III and WISC-IV, Stroop tests. METHODS: The study group consisted of children born prematurely who had been tested with Denver II and Bayley III in their first 2 years, and had been evaluated with WISC-IV and Stroop tests under follow up, 6-10 years later. RESULTS: The study group (n = 60, 25 F, 35 M) was 8.0 ± 2.4 (6-10.7) years old when given WISC-IV and Stroop tests. Gestational age in the study group was 34-37 weeks in 25%, 30-33 weeks in 48.3%, and <29 weeks in 26.7%. On WISC-IV, the verbal comprehension index, perceptual reasoning index, working memory index, and full-scale IQ scores were lower in the study group than the control group (P < 0.05). The study group took longer to complete the Stroop test (P < 0.05). Lower socioeconomic status (P = 0.005) and parental education level (P = 0.000) were associated with lower verbal comprehension index scores. Denver II and Bayley III test results were related to WISC-IV results (P < 0.05) but not to the Stroop test results (P > 0.05). CONCLUSIONS: Our results showed prematurity negatively influences the results of WISC-IV and Stroop tests at school age. Denver II and Bayley III tests applied at age 2 years likely predict WISC-IV results.

Efficacy of levetiracetam in the treatment of Sydenham chorea.

BACKGROUND: To study the effect of levetiracetam in treating Sydenham chorea. METHODS: We retrospectively collected the data of 140 patients diagnosed with Sydenham chorea in the pediatric neurology and pediatric cardiology outpatient clinics of Van Training and Research Hospital between January 2010 and December 2018. RESULTS: There were 140 patients, 102 (70%) of whom were girls, with mean age of onset 11.8 ± 2.7 years. Symptomatic treatment was initiated in all patients at the time of diagnosis; this medication was changed during follow up in 15 patients. The most frequently prescribed drugs were haloperidol and sodium (Na) valproate, and the most frequently discontinued one was haloperidol, due to side effects. The second-choice drug was most often levetiracetam. Clinical response often began within the first 2 weeks, with Na valproate (P = 0.002), within 4 weeks with carbamazepine (P = 0.037) but 1-6 months with haloperidol (P = 0.018) and levetiracetam (P = 0.008). Time to full remission was similar with Na valproate, carbamazepine, haloperidol, and levetiracetam (P = 0.276). Our study indicated that levetiracetam was as effective as the other commonly used drugs in the symptomatic treatment of Sydenham chorea. CONCLUSION: Levetiracetam might be an option in the treatment of Sydenham chorea because of its acceptable effect and safety profile. This observation needs further support with evidence obtained through controlled and blinded trials.

Cognitive profile and academic achievement of children with absence epilepsy.

The main aim of this study was to examine the cognitive profile and academic achievement of children with absence epilepsy. It is investigated whether all scale intelligence score, intelligence subscale scores, and academic achievement of the children with absence epilepsy differed from healthy peers and Turkish norm values. Nineteen children with absence epilepsy and 19 healthy children participate in the study. The Wechsler Intelligence Scale for Children-IV (WISC-IV) is used to measure their intelligence scores. A teacher assessment form (Teacher's Report Form (TRF)) is obtained from the participants' teachers for the measurement of academic achievement, and the students' report cards are collected as an additional measure of it. Participants with absence epilepsy have significantly lower scores of total intelligence score (Mean (M) = 76.68, Standard Deviation (SD) = 25.18), verbal comprehension score (M = 81.68, SD = 25.29), perceptual reasoning score (M = 85.47, SD = 20.61), processing speed score (M = 77.95, SD = 18.61), and working memory (M = 83.74, SD = 19.04), which are measured by WISC-IV, than healthy peers (respectively M = 105.84, SD = 16.20; M = 105.47, SD = 18.12; M = 103.63, SD = 12.88; M = 104.05, SD = 12.98; M = 104.74, SD = 18.97) and norm values (M = 100, SD = 10). No difference is observed between the subscale scores of WISC-IV for within group with absence epilepsy. Moreover, they have lower Turkish language (M = 73.65, SD = 19.19) and mathematics (M = 76.26, SD = 22.29) grade report scores than healthy peers (respectively M = 90.76, SD = 12.01; M = 88.64, SD = 15.93). There is no difference between the two groups in terms of the academic achievement obtained from the TRF. It is necessary to support children with absence epilepsy academically. We analyzed whether the current pattern has changed by comparing the intelligent scores and academic achievement of children with absence epilepsy who have recovered after treatment with their healthy peers. In fact, there is no difference between the children with absence epilepsy who have recovered after treatment and their healthy peers in terms of total intelligence score and its subscale scores. Similarly, there is no difference between them in terms of mathematics score on their report. Only the difference in the score of Turkish language continues in the same direction.

A rare concurrence: gelastic seizures in a patient with right temporal nongalenic pial arteriovenous fistula.

INTRODUCTION: Gelastic seizures are the type of seizures that are most commonly seen in childhood and should be excluded definitely in the differential diagnosis of hypothalamic hamartomas. This seizure type may be accompanied by refractory seizures, cognitive decline, and early puberty. However, etiology may also include other causes different than hypothalamic hamartomas. The seizure may also arise from temporal and frontal region, in addition to hypothalamus. Different clinical findings may be observed based on origin and areas of spread. CONCLUSIONS: In this article, we report a case of gelastic seizure that has been observed by a different cause other than hypothalamic hamartoma which was reported for the first time in the literature.

Does Levetiracetam Administration Prevent Cardiac Damage in Adulthood Rats Following Neonatal Hypoxia/Ischemia-Induced Brain Injury?

Cardiovascular abnormalities are widespread when a newborn is exposed to a hypoxic-ischemic injury in the neonatal period. Although the neuroprotective effects of levetiracetam (LEV) have been reported after hypoxia, the cardioprotective effects of LEV have not been documented. Therefore, we aimed to investigate whether levetiracetam (LEV) has a protective effect on cardiac-contractility and ultrastructure of heart muscle in rats exposed to hypoxia-ischemia (HI) during the neonatal period. A total of 49 seven-day-old rat pups were separated into four groups. For HI induction, a combination of right common carotid artery ligation with 8% oxygen in seven-day-old rat pups for 2 h was performed for saline, LEV100, and LEV200 groups. Just after hypoxia, LEV100 and LEV200 groups were administered with 100 mg/kg and 200 mg/kg of LEV, respectively. The arteries of rats in the control group were only detected; no ligation or hypoxia was performed. At the end of the 16th week after HI, cardiac mechanograms were recorded, and samples of tissue were explored by electronmicroscopy.While ventricular contractility in the control group was similar to LEV100, there were significant decreases in both saline and LEV200 groups (p < 0.05). Although ventricular contractile duration of the control and saline groups was found to be similar, durations in the LEV100 and LEV200 groups were significantly higher (p < 0.05). After HI, mitochondrial damage and ultrastructural deteriorative alterations in ventricles and atriums of the LEV-administered groups were significantly less severe than the saline group. The present study showed that neonatal HI caused long-term cardiac dysfunction and ultrastructural deteriorations in cardiac muscles. LEV administration just after HI might possess some protective effects against myocardial damage and contractility.

Sleep problems in pediatric epilepsy and ADHD: The impact of comorbidity.

AIMS: Attention-deficit hyperactivity disorder (ADHD) is a frequent comorbidity in pediatric epilepsy. Although sleep problems are commonly reported in both children with primary ADHD and epilepsy, those with epilepsy-ADHD comorbidity have not been well studied. This study aimed to compare sleep problems among three groups of children: 1) children with epilepsy, 2) children with epilepsy and ADHD (epilepsy-ADHD), and 3) children with primary ADHD. METHODS: 53 children with epilepsy, 35 children with epilepsy-ADHD, and 52 children with primary ADHD completed the Children's Sleep Habits Questionnaire (CSHQ). Neurology clinic charts were reviewed for the epilepsy-related variables. ADHD subtypes were diagnosed according to the DSM-IV. RESULTS: Children with epilepsy-ADHD had the highest CSHQ total scores, while children with primary ADHD had higher scores than those with epilepsy. Besides the total score, epilepsy-ADHD group differed from the primary ADHD and epilepsy groups with higher CSHQ subscores on sleep onset delay and sleep anxiety. The frequency of moderate-severe sleep problems (CSHQ>56) was 62.9% in children with epilepsy-ADHD, while it was 40.4% and 26.4% in children with primary ADHD and epilepsy, respectively. CSHQ total scores were not different between ADHD subtypes in both children with epilepsy-ADHD and those with primary ADHD. None of the epilepsy-related variables were found to be associated with CSHQ scores. DISCUSSION: Epilepsy-ADHD is associated with a significantly poor sleep quality which is beyond that of primary ADHD and epilepsy.

Sleep and quality of life in children with traumatic brain injury and ADHD.

Objective Attention problems are common in children who sustain a traumatic brain injury (TBI). The differential features of TBI-related Attention Deficit Hyperactivity Disorder (ADHD) and primary ADHD are largely unknown. This study aimed to compare sleep problems and quality of life between children with TBI and ADHD and children with primary ADHD. Methods Twenty children with TBI (mean age = 12.7 ± 3.1 years) who had clinically significant ADHD symptoms according to the structured diagnostic interview and rating scales and a control group with primary ADHD (n = 20) were included. Parents completed Children's Sleep Habits Questionnaire (CSHQ) and Kinder Lebensqualitätsfragebogen: Children's Quality of Life Questionnaire-revised (KINDL-R). Neurology clinic charts were reviewed for TBI-related variables. Results When compared to children with primary ADHD, the Total Score and Sleep Onset Delay, Daytime Sleepiness, Parasomnias, and Sleep Disordered Breathing subscores of CSHQ were found to be higher in children with TBI and ADHD. The Total Score and Emotional Well-Being and Self-Esteem subscores of the KINDL-R were found to be low (poorer) in children with TBI and ADHD. The Total Score and certain subscores of KINDL-R were found to be lower in TBI patients with a CSHQ > 56 (corresponds to significant sleep problems) when compared to those with a CSHQ < 56. CSHQ Total Score was negatively correlated with age. Conclusion Children with TBI and ADHD symptoms were found to have a poorer sleep quality and quality of life than children with primary ADHD. ADHD in TBI may be considered as a highly impairing condition which must be early diagnosed and treated.

Comparison of selective head cooling versus whole-body cooling.

BACKGROUND: This study compared selective head cooling (SHC) and whole-body cooling (WBC) in newborns with hypoxic-ischemic encephalopathy (HIE). METHODS: We conducted a prospective randomized small-scale pilot study in newborns with HIE, born after >35 weeks of gestation. The patients were randomly assigned to receive SHC or WBC. RESULTS: The SHC group consisted of 17 patients, and the WBC group, 12 patients. There was no significant difference in adverse effects related to cooling therapy between the two groups. During the 12 month study period, seven patients in the SHC group and four in the WBC group died, but the difference was not significant (P = 0.667). Among the patients alive at 12 months after treatment, six in the SHC group and four in the WBC group had severe disabilities; the difference was not significant (P = 0.671). When the composite outcome of death or severe disability was evaluated, the difference between the SHC group (77%, n = 13) and the WBC group (67%, n = 8) was not significant (P = 0.562). Moreover, the number of survivors without disability at 12 months after treatment did not differ significantly between the SHC group (n = 3) and the WBC group (n = 4; P = 0.614). CONCLUSIONS: There were no significant differences in adverse effects, 12 month neuromotor development, or mortality rate between SHC and WBC in newborns with HIE, born after >35 weeks of gestation.

Neuroprotective effect of levetiracetam on hypoxic ischemic brain injury in neonatal rats.

PURPOSE: Hypoxic-ischemic brain injury that occurs in the perinatal period is one of the leading causes of mental retardation, visual and auditory impairment, motor defects, epilepsy, cerebral palsy, and death in neonates. The severity of apoptosis that develops after ischemic hypoxia and reperfusion is an indication of brain injury. Thus, it may be possible to prevent or reduce injury with treatments that can be given before the reperfusion period following hypoxia and ischemia. Levetiracetam is a new-generation antiepileptic drug that has begun to be used in the treatment of epilepsy. METHODS: The present study investigated the effects of levetiracetam on neuronal apoptosis with histopathological and biochemical tests in the early period and behavioral experiments in the late period. RESULTS: This study showed histopathologically that levetiracetam reduces the number of apoptotic neurons and has a neuroprotective effect in a neonatal rat model of hypoxic-ischemic brain injury in the early period. On the other hand, we demonstrated that levetiracetam dose dependently improves behavioral performance in the late period. CONCLUSIONS: Based on these results, we believe that one mechanism of levetiracetam's neuroprotective effects is due to increases in glutathione peroxidase and superoxide dismutase enzyme levels. To the best of our knowledge, this study is the first to show the neuroprotective effects of levetiracetam in a neonatal rat model of hypoxic-ischemic brain injury using histopathological, biochemical, and late-period behavioral experiments within the same experimental group.

Consistency between referral diagnosis and post-ENMG diagnosis in children.

OBJECTIVE: To evaluate the degree of consistency between the referral diagnosis and that based on electroneuromyography. METHODS: The retrospective study was conducted at the Paediatric Neurology Laboratory of Mersin University School of Medicine, Turkey, and comprised all electroneuromyographies carried out between January 2005 and December 2010. Demographic data, referral diagnosis and post-procedure diagnosis were recorded for each patient, and were classified into groups. Consistency between the two groups was compared using SPSS 13. RESULTS: Of the total 294 patients, polyneuropathy was the reason for referral in 104 (35.4%), peripheral nerve injury in 54 (18.4%), brachial plexus injury in 52 (17.7%), myopathy in 52 (17.7%), hypotonia in 23 (7.8%), and facial paralysis in 9 (3.0%) patients. There was consistency between the two diagnoses in 179 (60.9%) patients. CONCLUSION: Electroneuromyography is an uneasy, painful and stressfull procedure for children, and, therefore, it should be recommended only in cases where the result may be beneficial in the diagnosis treatment and follow-up of a patient.

A Novel Mutation Diagnosing in Allan-Herndon-Dudley's Syndrome.

Allan-Herndon-Dudley's syndrome (AHDS) is a rare X-linked recessive disease that causes abnormal serum thyroid function tests, severe hypotonia, intellectual disability, and motor deficit due to a mutation in the monocarboxylate transporter 8, which is a thyroid hormone transporter. A 6-month-old male patient presented to our outpatient clinic with a serious hypotonia complaint. With a preliminary diagnosis of AHDS, a molecular genetic examination was performed. The molecular genetic analysis detected a new previously unidentified variant in the SLC16A2 gene. This case has been presented to report the AHDS, which is a rare cause of hypotonia in patients presenting/consulting with severe hypotonia, global developmental delay, and abnormal thyroid function test results. Besides, a novel pathogenic mutation in the SLC16A2 gene has been described in the present article.

Two Sibling Cases of Spastic Paraplegia-45 with a Novel Pathogenic Variant in NT5C2 Gene: Concomitant RYR1 Gene in One Sibling.

Introduction: Hereditary spastic paraplegia (SPG) is a genetically and clinically heterogeneous group of rare neurodegenerative disorders. SPG45 is the AR inherited type of complicated SPG, which is due to a mutation in the NT5C2 gene. Case Presentation: Two sisters, aged 8 and 4, exhibited delayed motor development since early childhood. They also experienced learning difficulties, dysarthric speech, ataxia, nystagmus, strabismus, and spasticity in their extremities. Additionally, brisk deep tendon reflexes were observed in their upper and lower limbs, and they exhibited positive pathological reflexes. Whole-exome sequencing identified a previously unidentified homozygous mutation in the NT5C2 gene, leading to the diagnosis of SPG45 in both siblings. A mutation in the RYR1 gene associated with malignant hyperthermia was also detected in one of the siblings, necessitating ongoing monitoring. Discussion/Conclusion: To the best of our knowledge, we report the first case of a patient with coexistence of the NT5C2 gene and the RYR1 gene.