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.

Alterations in the tear film and ocular surface in pediatric migraine patients.

PURPOSE: To evaluate the ocular surface (OS) parameters in the pediatric migraine patients (PMPs). METHODS: This prospective case-control study consisted of 51 PMPs (PMP group) and 55 healthy pediatric patients (HPP group). In all participants, tear function was evaluated subjectively using the Ocular Surface Disease Index (OSDI) questionnaire, objectively using Schirmer tear test (STT) and tear film disintegration time (TBUT), and with clinical and laboratory examinations (conjunctival impression cytology). The PMP group was subdivided into two groups according to their aura. RESULTS: The mean age and gender distribution of the study groups were almost the same ( P > 0.05 for both of them). In the PMP group, both the STT value and the TBUT value were significantly lower than those determined in the HPP group ( P = 0.021 and P = 0.018, respectively). In the PMP group, the OSDI scores were higher than those in the HPP group ( P = 0.032). In the PMP group, the goblet cell density values were lower than those in the HPP group ( P = 0.01). With regard to the aura, the TBUT and STT values were nonsignificantly lower in the PMP aura-positive group than in the PMP aura-negative group ( P > 0.05 for both of them). The OSDI assessment was similar in both the groups. With regard to the goblet cell count, it was observed to be less in the PMP aura-positive group than in the PMP aura-negative group ( P = 0.01). CONCLUSION: Influence of OS in children with migraine was also demonstrated using the samples taken from the conjunctiva. These changes were also demonstrated by objective tests such as STT and TBUT. Both clinical objective evaluations and pathologic changes were more prominent in the migraine with aura group.

Biallelic NAA60 variants with impaired n-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications.

Primary familial brain calcification (PFBC) is characterized by calcium deposition in the brain, causing progressive movement disorders, psychiatric symptoms, and cognitive decline. PFBC is a heterogeneous disorder currently linked to variants in six different genes, but most patients remain genetically undiagnosed. Here, we identify biallelic NAA60 variants in ten individuals from seven families with autosomal recessive PFBC. The NAA60 variants lead to loss-of-function with lack of protein N-terminal (Nt)-acetylation activity. We show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro. In cells, loss of NAA60 caused reduced surface levels of SLC20A2 and a reduction in extracellular phosphate uptake. This study establishes NAA60 as a causal gene for PFBC, provides a possible biochemical explanation of its disease-causing mechanisms and underscores NAA60-mediated Nt-acetylation of transmembrane proteins as a fundamental process for healthy neurobiological functioning.

A Multicenter Study of Self-Limited Epilepsy With Centrotemporal Spikes: Effectiveness of Antiseizure Medication With Respect to Spike-Wave Index.

BACKGROUND: There is no certain validated electroencephalographic (EEG) parameters for outcome prediction in children with self-limited epilepsy with centrotemporal spikes. To assess the effectiveness of antiseizure medication (ASM) for seizure outcome with respect to the spike-wave index (SWI) on serial EEG recordings. METHODS: In this multicenter study, the study cohort consisted of 604 children with self-limited epilepsy with centrotemporal spikes. A data set of epilepsy centers follow-up between 2010 and 2022. The cohort was divided into 4 groups as those receiving 3 different monotherapy (carbamazepine [CBZ]/valproic acid [VPA]/levetiracetam [LEV]) and dual therapy. SWI analysis was performed with the percent of spikes in the 2-minute epoch in the 5th 6th minutes of the nonrapid eye movement sleep EEG record. The study group were also categorized according to seizure burden with seizure frequency (I) >2 seizures and (II) >5 seizures. Seizure outcome was evaluated based on the reduction in seizure frequency over 6-month periods: (1) 50% reduction and (2) seizure-free (complete response). RESULTS: ASM monotherapy was achieved in 74.5% children with VPA, CBZ, and LEV with similar rates of 85.8%, 85.7%, and 77.9%. Dual therapy was need in the 25.5% of children with SeLECT. More dual therapy was administered in children aged below 5 years with a rate of 46.2%. Earlier seizure-free achievement time was seen in children with LEV monotherapy with more complete-response rate (86.7%) compared the VPA and CBZ. CONCLUSIONS: We also determined that the children on dual therapy had more SWI clearance in the subsequent EEG recordings. The ROC curve analyses were performed to predict initial drug selection with using the SWI% might be used for the prediction of ASM type and drug selection in children.

Case Report of Two Siblings Diagnosed with Osteogenesis Imperfecta Type XV with a New Mutation in the WNT1 Gene and Review of the Literature.

Introduction: Osteogenesis imperfecta (OI) is a heritable disorder characterized by bone fractures and low bone mass. Recently, mutations of the WNT1 gene have been reported to be causative in OI. The mutation in WNT1 causes autosomal-recessive OI due to its critical role in bone formation. WNT1 mutations cause varying degrees of clinical severity, ranging from moderate to progressively deforming forms. In addition to the OI phenotype, our cases also had extra-skeletal findings. Case Presentation: We describe two siblings with multiple fractures and developmental delay. A novel homozygous frameshift WNT1 mutation was detected in this family, and we reviewed the literature for WNT1-related OI cases. Discussion: We report a novel variant with a clinical diagnosis of severe OI, and this review will provide a comprehensive overview of previously published cases of OI type XV. With a better understanding of disorders associated with WNT1 mutations, therapies targeting Wnt1 signaling pathway may contribute therapeutic benefits.

Evaluation of developmental profiles of children with hydrocephalus.

OBJECTIVE: The objective of this study was to compare the developmental characteristics of children with hydrocephalus with those of healthy children. MATERIAL AND METHODS: A total of 109 children aged between 2 and 46 months were included in the study, 54 patients diagnosed with hydrocephalus and 55 healthy children were evaluated with demographic data forms and Denver Developmental Screening Test II. RESULTS: The mean personal-social (p<0.001), fine motor-adaptive (p<0.001), language (p<0.001), and gross motor subscale scores were significantly lower in children with hydrocephalus than in the control group. Personal-social (p=0.002) and gross motor (p=0.029) subscale scores were significantly lower in children with obstructive hydrocephalus than communicating hydrocephalus. There was a significant negative correlation between language scores and ages of the children with hydrocephalus (r=-0.350, p=0.009). It was found that children with obstructive hydrocephalus carry a 6.7 folds higher risk of experiencing problems in terms of personal-social development compared to those with communicating hydrocephalus (p=0.011). CONCLUSION: We found that patients with hydrocephalus were developmentally retarded compared to the healthy control subjects. Retardation was the most prominent in the obstructive group. Our results showed that neurodevelopmental follow-up should be carried-out regularly in pediatric patients with hydrocephalus, and early intervention should be started in necessary cases.

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.

Beliefs and behaviors of patients' relatives towards childhood epilepsy in Turkey.

BACKGROUND/AIM: Beliefs about health-related problems throughout history are conveyed differently. Unsafe practices based on the superstitious beliefs of patients' relatives in situations requiring emergency medical attention, such as childhood epilepsy, or in the treatment of chronic diseases may be harmful to children's health. Our study aims to determine the superstitious beliefs, attitudes, and behaviours of the relatives of children with epilepsy. METHODS: A total of 252 relatives of patients diagnosed with childhood epilepsy were included in this cross-sectional study conducted between 15 September and 15 October 2019. The data collection form contained questions about the sociodemographic information of the participants and their beliefs and behaviours towards the disease. The frequency (percentage) and mean were used to summarise the data obtained through the application of the questionnaire, and Student's t-test and correlation methods were used for group comparisons; p < 0.05 was considered statistically significant. RESULTS: In the study, 77.0% of the participants were women, 77.4% were mothers, 43.3% were primary school graduates, 71.8% were unemployed, 77.7% had a low income, 52% lived within a distance of less than 1 km, and 157 of them used folk medicine. There was no relationship between education, income, distance from health institutions, occupation, use of traditional methods, and superstitions. A relationship was found between the relatives of patients with resistant epilepsy who stated that the cause of the disease was superstition (p = 0.036). There was also a correlation between the use of traditional methods (p = 0.006), presence of resistant epilepsy, indication of the cause of the disease as superstition (p = 0.004), and use of traditional methods (p = 0.005). CONCLUSION: Our study shows that approximately four-fifths of the participants had superstitious beliefs about epilepsy and exhibited attitudes and behaviours suggestive of neglect that are unsafe for children. Whilst the individual characteristics of the participants did not affect negative attitudes and behaviours, the presence of resistant epilepsy in their children increased the negative attitude tendency.

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.

Developmental evaluation in children experiencing febrile convulsions.

BACKGROUND: The objective of this study was to determine the effect of febrile convulsion (FC) on neuromotor development. METHODS: Data of 325 patients, who were followed up at our outpatient clinic and diagnosed with FC between January 2012 and December 2018, were retrospectively evaluated. Of these patients, 203 underwent the Denver Developmental Screening Test II (DDST II) and were included in the study as the patient group and 100 healthy children as the control group. RESULTS: Of the study group, 84 (41.4%) were girls and 119 (58.6%) were boys (B/G: 1.4). Of all patients, 163 (80.3%) were diagnosed with simple FC, 22 (10.8%) with complicated FC, and 18 (8.9%) with FC+. There was no significant relationship found between FC subtypes and gender, family history of FC, family history of epilepsy, iron (Fe) deficiency, and Fe deficiency anemia. DDST II subtest points were significantly lower in all developmental areas in the patient group when compared to the controls (p < 0.001), while suspected and abnormal test results were higher in all developmental areas in the patient group compared to the controls (p=0.01). It was also determined that the language points were lower as the age of first seizure increased (r=- 0.319, p < 0.01). CONCLUSIONS: Although FC is known to usually having a good prognosis, the low DDST II test results measured in this study indicated that the FC may pose a developmental risk and patients with FC should be followed up in terms of developmental features. Because of the retrospective nature of the study, there was no `preconvulsion` developmental evaluation. This is a major limitation of our study.