Optic neuritis in Turkish children and adolescents: A multicenter retrospective study.

BACKGROUND: Various etiologies may underlie optic neuritis, including autoantibody-mediated disorders described in the last decade. We re-examined demographic, clinical, laboratory features and prognostic factors in pediatric patients with autoimmune optic neuritis according to current knowledge. METHODS: Cases of pediatric ON from 27 centers in Türkiye diagnosed between 2009 and 2022 were included for retrospective evaluation. RESULTS: The study included 279 patients, 174 females and 105 males, with a female-to-male ratio of 1.65. The average age at onset was 12.8 ± 3.4 years, and mean follow-up, 2.1 years (range: 1-12.1 years). Patients <10 years old were grouped as "prepubertal" and those ≥10 years old as "others". The diagnoses made at the end of follow-up were multiple sclerosis associated optic neuritis (n = 90, 32.3 %), single isolated optic neuritis (n = 86, 31 %), clinically isolated syndrome (n = 41, 14.7 %), myelin oligodendrocyte glycoprotein antibody associated optic neuritis (n = 22, 7.9 %), and relapsing isolated optic neuritis (n = 18, 6.5 %). Predominant diagnoses were myelin oligodendrocyte glycoprotein antibody associated optic neuritis and acute disseminated encephalomyelitis associated optic neuritis in the prepubertal group and multiple sclerosis associated optic neuritis in the older group. Recurrences were observed in 67 (24 %) patients, including 28 with multiple sclerosis associated optic neuritis, 18 with relapsing isolated optic neuritis, 11 with myelin oligodendrocyte glycoprotein antibody associated optic neuritis, 8 with aquaporin-4 antibody related optic neuritis, and 2 with chronic relapsing inflammatory optic neuropathy. Recurrences were more common among female patients. Findings supporting the diagnosis of multiple sclerosis included age of onset ≥ 10 years (OR=1.24, p = 0.027), the presence of cranial MRI lesions (OR=26.92, p<0.001), and oligoclonal bands (OR=9.7, p = 0.001). Treatment in the acute phase consisted of intravenous pulse methylprednisolone (n = 46, 16.5 %), pulse methylprednisolone with an oral taper (n = 212, 76 %), and combinations of pulse methylprednisolone, plasmapheresis, or intravenous immunoglobulin (n = 21, 7.5 %). Outcome at 12 months was satisfactory, with 247 out of 279 patients (88.5 %) demonstrating complete recovery. Thirty-two patients exhibited incomplete recovery and further combination treatments were applied. Specifically, patients with relapsing isolated optic neuritis and aquaporin-4 antibody related optic neuritis displayed a less favorable prognosis. CONCLUSION: Our results suggest optic neuritis is frequently bilateral in prepubertal and unilateral in peri­ or postpubertal patients. Age of onset 10 or older, presence of oligoclonal bands, and brain MRI findings reliably predict the development of multiple sclerosis. The risk of developing multiple sclerosis increases mostly during the second and third years of follow-up. Relapsing isolated optic neuritis remains a separate group where the pathogenesis and outcome remain unclear. Investigation of predisposing and diagnostic biomarkers and long follow-up could help to define this group.

The Role of Breast Milk Neurotrophin Levels in Infantile Colic Pathogenesis: A Cross-Sectional Case-Control Study.

Objective: Immaturity of the digestive tract and enteric nervous system is a widely accepted theory for infantile colic (IC) etiopathogenesis. The study aimed to show whether neurotrophins that are necessary for normal functioning and development of the gastrointestinal system have a role in the pathogenesis of IC. Materials and Methods: The IC group (n = 75) comprising the mothers of infants with IC and the control group (n = 75) were included to this cross-sectional case-control study. Brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF), and nerve growth factor (NGF) levels of breast milk samples were evaluated by immunosorbent analysis method. Results: The mean age of infants with IC was 7.3 ± 2.8 weeks, while the mean age of the control group was 8.1 ± 2.9 weeks (p = 0.110). No significant difference was found between the breast milk BDNF, GDNF, CNTF, and NGF levels of two groups (p = 0.941, p = 0.510, p = 0.533, p = 0.839, respectively). Conclusions: This is the first report comparing the neurotrophin levels of the breast milk samples taken from the mothers of infants with and without IC. The study demonstrated that breast milk neurotrophin levels of the mothers did not differ significantly between the infants with and without IC.

Coronavirus Disease 2019-Associated Neurological Manifestations in Children: A Large Single-Center Experience With Rare Cases.

BACKGROUND: We aimed to analyze pediatric patients with coronavirus disease 2019 (COVID-19) with a diverse spectrum of neurological manifestations in a single center since neurological involvement in children is still poorly understood. METHODS: We performed a retrospective study on 912 children aged between zero and 18 years who had a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result and symptoms of COVID-19 from March 2020 to March 2021 in a single center. RESULTS: Among 912 patients, 37.5% (n = 342) had neurological symptoms and 62.5% (n = 570) had no neurological symptoms. The mean age of patients with neurological symptoms was significantly higher (14.2 ± 3.7 vs 9.9 ± 5.7; P < 0.001). Three hundred and twenty-two patients had nonspecific symptoms (ageusia, anosmia, parosmia, headache, vertigo, myalgia), whereas 20 patients had specific involvement (seizures/febrile infection-related epilepsy syndrome, cranial nerve palsy, Guillain-Barré syndrome and variants, acute disseminated encephalomyelitis, central nervous system vasculitis). The mean age of the patients with nonspecific neurological symptoms was significantly higher (14.6 ± 3.1 vs 7.7 ± 5.7; P < 0.001). CONCLUSION: This study presents a large number of patients with a diverse spectrum of neurological manifestations. The rare neurological manifestations reported in our study will contribute to better understanding the neurological involvement of SARS-CoV-2 in children. The study also points out the differences of SARS-CoV-2-related neurological manifestations between patients at different ages. Physicians should be alert about recognizing the early neurological manifestations of the SARS-CoV-2 in children.

Pediatric-Onset Chronic Inflammatory Demyelinating Polyneuropathy: A Multicenter Study.

BACKGROUND: To evaluate the clinical features, demographic features, and treatment modalities of pediatric-onset chronic inflammatory demyelinating polyneuropathy (CIDP) in Turkey. METHODS: The clinical data of patients between January 2010 and December 2021 were reviewed retrospectively. The patients were evaluated according to the Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society Guideline on the management of CIDP (2021). In addition, patients with typical CIDP were divided into two groups according to the first-line treatment modalities (group 1: IVIg only, group 2: IVIg + steroid). The patients were further divided into two separate groups based on their magnetic resonance imaging (MRI) characteristics. RESULTS: A total of 43 patients, 22 (51.2%) males and 21 (48.8%) females, were included in the study. There was a significant difference between pretreatment and post-treatment modified Rankin scale (mRS) scores (P < 0.05) of all patients. First-line treatments include intravenous immunoglobulin (IVIg) (n = 19, 44.2%), IVIg + steroids (n = 20, 46.5%), steroids (n = 1, 2.3%), IVIg + steroids + plasmapheresis (n = 1, 2.3%), and IVIg + plasmapheresis (n = 1, 2.3%). Alternative agent therapy consisted of azathioprine (n = 5), rituximab (n = 1), and azathioprine + mycophenolate mofetil + methotrexate (n = 1). There was no difference between the pretreatment and post-treatment mRS scores of groups 1 and 2 (P > 0.05); however, a significant decrease was found in the mRS scores of both groups with treatment (P < 0.05). The patients with abnormal MRI had significantly higher pretreatment mRS scores compared with the group with normal MRI (P < 0.05). CONCLUSIONS: This multicenter study demonstrated that first-line immunotherapy modalities (IVIg vs IVIg + steroids) had equal efficacy for the treatment of patients with CIDP. We also determined that MRI features might be associated with profound clinical features, but did not affect treatment response.

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.

Evaluation of Nonconvulsive Status Epilepticus and Nonconvulsive Seizures in a Pediatric Intensive Care Unit.

We aimed to identify nonconvulsive seizures (NCS) and nonconvulsive status epilepticus (NCSE) in a pediatric intensive care unit (PICU). A prospective cohort study on 35 patients who underwent continuous electroencephalographic monitoring in the PICU was done. The patients were evaluated to collect data of their demographics, clinical diagnoses, clinical seizures by electroencephalography, and neuroimaging findings. One case with NCSE and 4 cases with NCS were diagnosed among the 35 patients. The etiology of the patient with NCSE showed antiepileptic drug (AED) withdrawal. The etiology of the patients with NCS included electrical injury, head trauma, subarachnoid hemorrhage, and pneumonia. The findings suggest that younger age, epilepsy, acute structural brain abnormalities, abrupt cessation of AED, and clinically overt seizures before NCSE/NCS are associated with significant risk for NCS/NCSE. In addition, the electrical injury may also be considered as a risk factor for electrographic seizure though such a case has not yet been reported.

Resting Electroencephalography Differences Between Eyes-Closed and Eyes-Open Conditions in Children with Subclinical Hypothyroidism.

OBJECTIVE: Electroencephalography changes that occur during the transition from eyes-closed to the eyes-open state in resting condition are related to the early phase of sensory processing and are defined as activation. The present study aimed to reveal the potential deteriorations that may occur in the initial period of sensory processing in resting electroencephalography between children with subclinical hypothyroidism and a control group. MATERIALS AND METHODS: Electroencephalographies of 15 children with subclinical hypothyroidism and 15 healthy children aged 10 to 17 years were recorded for 2 minutes for EC and 2 minutes for eyes-open conditions in resting state. Absolute electroencephalography band powers (µV2 ) within the delta, theta, alpha, and beta frequency bands were calculated in Fz, Cz, Pz, and Oz electrodes, respectively, for eyes-closed and eyes-open conditions. RESULTS: The results show that, although there was no noteworthy difference between the powers of the electroencephalography frequency bands of children with subclinical hypothyroidism and healthy children during the eyes-open condition, the alpha powers of the control group were significantly higher in all electrodes during the eyes-closed condition. Furthermore, the powers of all frequency bands were observed to decrease in the eyes-open condition in the control group. However, the same net decrease was not observed in the frequency powers of children with subclinical hypothyroidism. CONCLUSION: According to the results of this study, children with subclinical hypothyroidism may experience information processing impairments starting in the early stages of sensory processing.

A female case of 5,10-methenyltetrahydrofolate synthetase deficiency with novel neuro-imaging abnormalities.

BACKGROUND: Folate metabolism disorders can affect various organ systems, including the nervous system. 5,10-methenyltetrahydrofolate synthetase deficiency is a rare cerebral folate deficiency in which MTHFS activity is disrupted with low-normal cerebrospinal fluid (CSF) 5,10-methenyltetrahydrofolate levels, while peripheral folate levels are normal. CASE REPORT: We present here a female patient with developmental delay, microcephaly, hypotonia, nystagmus, and seizure in which a distinct brain MRI and CT showed restricted diffusion in the bilateral parietal and occipital lobes, and calcifications of the bilateral putamen, globus pallidus, and caudate nucleus, and the bilateral parietal and occipital lobes. Laboratory tests revealed macrocytic anemia, increased homocysteine, low-normal CSF 5,10-methenyltetrahydrofolate, and low CSF folate, but normal serum vitamin B12 and folate levels. A whole exome sequencing analysis verified the diagnosis of 5,10-methenyltetrahydrofolate synthetase deficiency. CONCLUSIONS: We have added novel knowledge which is nystagmus and hypotonia in the clinical findings, the involvement and restriction of bilateral putamen, globus pallidus, parietal and occipital lobes, and calcification of the bilateral putamen, globus pallidus, caudate nucleus, and parietal and occipital lobes in neuroimaging images and also low CSF folate in the metabolic investigation with the patient in 5,10-methenyltetrahydrofolate synthetase deficiency.

The effectiveness and tolerability of clobazam in the pediatric population: Adjunctive therapy and monotherapy in a large-cohort multicenter study.

OBJECTIVE: To evaluate the effectiveness and tolerability of clobazam therapy in the pediatric population in terms of seizure semiology, epileptic syndromes, and etiological subgroups. METHODS: A retrospective cohort study was conducted consisting of 1710 epileptic children from eight centers in seven geographic regions of Turkey. The initial efficacy of clobazam therapy was evaluated after three months of treatment. The long-term effectiveness of the drug, overall seizure outcomes, and overall therapeutic outcomes were evaluated during 12 months of therapy. RESULTS: Analysis of initial efficacy after the first three months of clobazam therapy showed that 320 (18.7 %) patients were seizure-free, 683 (39.9 %) had > 50 % seizure reductions, and 297 (17.4 %) had < 50 % seizure reductions. A positive response (seizure-free and >50 % seizure reduction) was determined for focal-onset (62.3 %) seizures, epileptic spasms (61.5 %), and generalized onset seisures (57.4). The highest positive response rate among the epileptic syndromes was for self-limited epilepsy with centrotemporal spikes (SeLECTS). The highest negative response rate was for developmental and/or epileptic encephalopathies (DEEs). Magnetic resonance imaging (MRI) revealed a structural etiological diagnosis in 25.8 % of the cohort. A higher positive response rate was observed at MRI in patients with sequelae lesions than in those with congenital lesions. The seizure recurrence rate was higher in the patient group with epilepsy with genetic and metabolic causes, in individuals with more than one seizure type, and in those using three or more antiseizure drugs. CONCLUSIONS: This cohort study provides additional evidence that clobazam is an effective and well-tolerable drug with a high seizure-free rate (18.7 %), a significant seizure reduction rate (57.3 %), and with excellent overall therapeutic outcomes with a low seizure relapse rate and considerable reversible benefits in the pediatric population.

Experiences in the molecular genetic and histopathological evaluation of calpainopathies.

Calpainopathy is mainly characterized by symmetric and progressive weakness of proximal muscles. Several reports showed that the most common LGMD subtype is LGMDR1 or calpainopathy, which had previously been defined as LGMD2A. Until now, more than 500 likely pathogenic/pathogenic variants in the CAPN3 gene have been reported. However, a clear genotype-phenotype association had not yet been established and this causes major difficulties in predicting the prognosis in asymptomatic patients and in providing genetic counseling for prenatal diagnosis. In this report, we aimed to add new data to the literature by evaluating 37 patients with likely pathogenic/pathogenic variants for the detected variants' nature, patients' phenotypes, and histopathological features. As a result, the general clinical presentation of the 23 different variants was presented, the high frequency of NM_000070.3:c.550delA mutation in Exon 4 was discussed, and some novel genotype-phenotype associations were suggested. We have underlined that calpainopathy can be misdiagnosed with inflammatory myopathies histopathologically. We have also emphasized that, in young or adult patients with mild to moderate proximal muscle weakness and elevated CK levels, calpainopathy should be the first suspected diagnosis.

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.

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.

The comparison of regional spinal curvatures and movements in sitting posture in ambulatory children with cerebral palsy having minimal-to-moderate functional limitations.

AIM: To examine the regional spinal curvatures and movements in the sagittal and frontal planes during sitting position, and the ability to act independently in patients with CP and to compare the differences between children and adolescents with minimal-to-moderate functional limitations. METHOD: Twenty-one participants diagnosed with CP aged 5-16 years were included. The participants' Gross Motor Function Classification System (GMFCS) levels were determined and those at levels I (minimal functional limitation group: minFLG) or II-III (moderate functional limitation group: modFLG) were included. Spinal curvatures, mobilities, and inclinations in the sagittal and frontal planes were evaluated in the sitting position using a hand-held, computer-assisted non-invasive electromechanical device. Participants' functional independence levels were assessed with the Functional Independence Measure (WeeFIM). RESULTS: In the sagittal plane, there were no differences in terms of spinal curvatures between the minFLG and modFLG (p > 0.05). Spinal mobility degrees for flexion (thoracic and lumbar regions and total spine), extension (sacral region), and total spine mobility scores were significantly greater in the minFLG (p < 0.05). In the frontal plane, lumbar spinal curvature significantly increased, and total spine mobility in the right/left lateral motions and functional independence decreased in the modFLG (p < 0.05). INTERPRETATION: The children/adolescents with minimal functional limitations had greater spinal mobility during flexion, extension, and lateral flexions. Spinal curvatures were similar between groups in the sagittal plane. The lumbar region posture scores in the frontal plane observed as lordoscoliosis were higher, and functional independence was lower in the modFLG.

An Unexpected Cause of Ptosis: 22q11.2 Duplication Syndrome.

The chromosome 22q11.2 region is highly susceptible to both microdeletions and microduplications that have been known to be responsible for multiple congenital anomaly disorders. We describe a patient of 22q11.2 duplication syndrome presenting with bilateral ptosis who has normal psychomotor development. Cranial magnetic resonance imaging and electromyography with repetitive nerve stimulation were normal. Chromosome microarray analysis was performed, and the patient was found to have a de novo 2.8 Mb duplication at 22q11.21. To our knowledge, bilateral ptosis and normal psychomotor development with 22q11.2 duplication syndrome has not been described. The 22q11.2 duplication syndrome should be considered in the differential diagnosis of ptosis. This case report contributes to an expanding clinical spectrum of patients with 22q11.2 duplication syndrome.

Electrical Status Epilepticus During Slow-wave Sleep (ESES): Current Perspectives.

Electrical status epilepticus during slow-wave sleep (ESES) is an epilepsy syndrome with sleep-induced epileptic discharges and acquired impairment of cognition or behavior. Since the disease's original description in 1971, no clear consensus has emerged on diagnostic criteria or optimal treatment. The treatment of ESES can be challenging, often including numerous antiepileptic drugs, immunomodulatory agents, and even surgical interventions. There is little evidence to guide treatment because only retrospective studies and case reports on the efficacy of treatment of ESES are present in literature. In this paper, we aim to analyze the etiopathogenesis of ESES in the new genetic era and to evaluate the treatment modalities in accordance with the genetic data and electroclinic spectrum of ESES.

A Neurological Appearance of Celiac Disease: Is There Any Associated Factor?

OBJECTIVE: Celiac disease may present with one or more neurological signs and/or symptoms. We aimed to define the incidence of accompanying neurological manifestations in children diagnosed as having celiac disease. METHODS: The prospective study included 146 children diagnosed as having celiac disease. The medical records (presentation symptoms, clinical findings, serological test, duodenal biopsy results, lack/deficiency of vitamin, tissue type, accompanying autoimmune disorders) and demographic data of all patients were also reviewed. RESULTS: Thirty-five (23.9%) of the 146 celiac patients exhibited one or more neurological findings. Headache (11.6%) and dizziness (6.1%) were the most common symptoms among neurological manifestations. There was a significant difference between the patients with and without neurological manifestations in terms of sex, biopsy result, and tissue type (P < 0.05). Moreover, there was a statistically significant difference between tissue types of the patients with and without headache (P < 0.05). We found that grade 3a by Marsh classification was the most common type among the patients with and without neurological findings in celiac disease. On neuroimaging evaluation of patients, 1 patient with chronic focal ischemic lesion, 1 patient with Chiari type 1 malformation, and 1 patient with subcortical white matter changes were identified. CONCLUSIONS: Pathophysiology of neurological involvement in celiac disease is liable for various neurological findings. This study contributes to data suggesting that female sex, mild histopathological form, and human leukocyte antigen DQ2 heterozygosity are related to neurological manifestations, and also human leukocyte antigen DQ2 heterozygosity is associated with headache in celiac disease.

Investigation of the most common clinical and imaging findings and the role of tubulin genes in the etiology of malformations of cortical development

Background and aim: The number of reports on the role of tubulin gene mutations (TUBA1A, TUBB2B, and TUBB3) in etiology of malformations of cortical development has peaked in recent years. We aimed to determine tubulin gene defects on a patient population with simple and complex malformations of cortical development, and investigate the relationship between tubulin gene mutations and disease phenotype. Materials and methods: We evaluated 47 patients with simple or complex malformations of cortical development, as determined by radiological examination, for demographic features, clinical findings and mutations on TUBA1A, TUBB2B, and TUBB3 genes. Results: According to the magnetic resonance imaging findings, 19 patients (40.5%) had simple malformations of cortical development and 28 (59.5%) patients had complex malformations of cortical development. Focal cortical dysplasia was the most common simple malformation, lissencephaly was the most common coexisting cortical malformation, and corpus callosum anomalies were the most common coexisting extracortical neurodevelopmental abnormalities. None of the patients had genetic alterations on TUBA1A, TUBB2B, and TUBB3 genes causing protein dysfunction. On the other hand, the frequencies of some polymorphisms were higher when compared to the literature. Conclusion: It is crucial to identify the etiology in patients with malformations of cortical development in order to provide appropriate genetic counseling and prenatal diagnosis. We consider that multicenter studies with higher patient numbers and also including other malformations of cortical development-related genes are required to determine underlying etiological factors of malformations of cortical development patients.

A Case with Neonatal-onset Type 2 Neuronal Ceroid Lipofuscinosis: A Novel Mutation.

Neuronal ceroid lipofuscinosis (NCL) is a lysosomal storage disorder that causes progressive neurodegenerative disease as a result of storage in neurons and other cells. Late infantile type (NCL Type 2) of NCL, which is the most common neurodegenerative disease in childhood, is characterised by a homozygous mutation in the tripeptidyl peptidase-1 (TPP-1) gene. A male infant was referred to our neonatal intensive care unit (NICU) on 26th day of life with a diagnosis of metabolic disease. He was intubated. He was hypotonic and newborn reflexes were not present. Cranial magnetic resonance (MR) imaging revealed severe atrophy and delayed myelination of cerebellum and cerebral hemispheres. A novel homozygous pathological mutation was detected in exon 9 of the TPP-1 gene. With this case, it should be kept in mind that NCL may rarely start early in neonatal period and should be suspected in newborns with cerebral and cerebellar atrophy for early diagnosis. Key Words: Hypotonia, Lysosomal storage diseases, Metabolic disease, Neuronal ceroid lipofuscinosis, Newborn.

Variant ataxia-telangiectasia in a child presenting with laryngeal dystonia.

BACKGROUND: Dystonia is a common hyperkinetic movement disorder in children; however, making an early and definitive diagnosis of dystonia can sometimes be challenging for clinicians. CASE: Herein, we report a case of a 16 years-old girl presenting with laryngeal dystonia due to compound heterozygosity of a known pathogenic and a novel variant in the ATM gene. Serum alpha-fetoprotein level was elevated. Serum IgG, IgA, IgM and IgE levels were within normal range. Treatment with L-DOPA had no benefit. Her symptoms were dramatically improved by localized botulinum toxin injections. CONCLUSION: Mutations in the ATM gene show a wide phenotypic spectrum from severe classical early-onset ataxia-telangiectasia (A-T) to late-onset milder variant A-T. Our findings highlight the importance of recognizing laryngeal dystonia as one of the clinical signs of A-T.