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Gilles de la Tourette syndrome (TS) is a common, childhood-onset psychiatric disorder characterized by persistent motor and vocal tics. It is a heterogeneous disorder in which the phenotypic expression may be affected by environmental factors, such as immune responses. Furthermore, several studies have shown that genetic factors play a vital role in the etiology of TS, as well as its comorbidity with other disorders, including attention deficit hyperactivity disorder, obsessive-compulsive disorder, and autism spectrum disorder. TS has a complex inheritance pattern and, according to various genetic studies, several genes and loci have been correlated with TS. Genome-wide linkage studies have identified Slit and Trk-like 1 (SLITRK1) and histidine decarboxylase (HDC) genes, and candidate gene association studies have extensively investigated the dopamine and serotonin system genes, but there have been no consistent results. Moreover, genome-wide association studies have implicated several genetic loci; however, larger study cohorts are needed to confirm this. Copy number variations, which are polymorphisms in the number of gene copies due to chromosomal deletions or duplications, are considered another significant source of mutations in TS. In the last decade, whole genome/exome sequencing has identified several novel genetic mutations in patients with TS. In conclusion, more studies are needed to reveal the exact mechanisms of underlying TS, which may help to provide more information on the prognosis and therapeutic plans for TS.

Epilepsy is a chronic neurological disorder that presents as recurrent, unprovoked seizures. Pharmacotherapy is the main treatment for epilepsy, but at least 30% of patients with epilepsy have pharmacoresistant epilepsy. Therefore, non-pharmacological treatments are still required. In addition to electrophysiological aberrations contributing to epileptogenesis and pathophysiology in epilepsy, neuroinflammation, oxidative stress, and metabolic derangement have been investigated as drug targets in the treatment of epilepsy. Vitamins have antioxidant, anti-inflammatory, and immunomodulatory effects, which can be beneficial for the treatment of epilepsy. Herein, we comprehensively review the role of vitamins in epilepsy. Certain epilepsies are vitamin-dependent or vitamin-responsive. Most studies on vitamins in epilepsy are of low evidence level or limited to animal studies. Nevertheless, vitamin supplementation should be considered in epilepsy therapy. Additionally, certain anti-seizure medications may alter the serum levels of certain vitamins. Monitoring the serum levels of vitamins and supplementing vitamins when needed are suggested during the follow-up of patients with epilepsy.

Gilles de la Tourette's Syndrome (TS) is a childhood-onset disease with clinical features of motor and phonic tics. Yi-Gan-san (YGS) is a traditional Chinese medicine formula that can reduce aggressiveness and agitation and inhibit dopamine function. This study investigated the effects of YGS on the psychiatric behavior of children and adolescents with TS.A double-blind, randomized, controlled preliminary study was conducted. A total of 38 patients with TS were assigned to the control group (CG, 19 patients) who received the oral administration of YGS placebo (90% starch and 10% YGS; 2.5 g thrice daily) or to a treatment group (TG, 19 patients) who received YGS for 4 weeks. The primary outcome measure was the change in Yale Global Tic Severity Scale (YGTSS) overall and subscale scores.The intensity score for phonic tics before oral administration of YGS, and after 2 weeks, 3 weeks and 4 weeks was not significantly different between CG and TG groups (2.94 ± 1.14 vs 2.79 ± 1.08, p = .686; 2.29 ± 1.21 vs 1.95 ± 1.08, p = .370; 2.41 ± 1.18 vs 2.05 ± 1.51, p = .435; and 2.29 ± 1.26 vs 1.84 ± 1.42, p = .323, respectively), while the intensity score for phonic tics after 1-week oral administration of YGS in the TG was 1.89 ± 1.10 lower than 3.06 ± 1.39 in the CG (p = .008).Oral administration of YGS for 1 week only reduced the intensity of phonic tics compared with oral administration of YGS placebo, suggesting that YGS can reduce their intensity for a short period, and the compliance of oral administration of YGS for 4 weeks can be accepted in children and adolescents with Tourette's Syndrome. However, because this study was preliminary, the selection of an appropriate placebo and dosage and long-term observations are crucial areas for future studies.

Ethnopharmacological relevance Muscular dystrophies are a rare, severe, and genetically inherited group of disorders characterized by progressive loss of muscle fibers, leading to muscle weakness. The current treatment plan for muscular dystrophies includes the use of steroids to slow muscle deterioration by dampening the inflammatory response. Aim of the study Chinese herbal medicine (CHM) has been offered as an adjunctive therapy in Taiwan's medical healthcare plan, making it possible to track CHM usage in patients with muscular dystrophic disease. Therefore, we explored the long-term effects of CHM use on the overall mortality of patients with muscular dystrophies. Materials and methods A total of 581 patients with muscular dystrophies were identified from the database of Registry for Catastrophic Illness Patients in Taiwan. Among them, 80 and 201 patients were CHM users and non-CHM users, respectively. Student's t-test, chi-squared test, Cox proportional hazard model, and Kaplan–Meier curve (log-rank test) were used for evaluation. Association rules and network analyses were performed to explore the combination of CHMs used in muscular dystrophies. Results Compared to non-CHM users, there were more female patients, more comorbidities, including chronic pulmonary disease and peptic ulcer disease in the CHM user group. Patients with prednisolone usage exhibited a lower risk of overall mortality than those who did not, after adjusting for age, sex, use of CHM, and comorbidities. CHM users showed a lower risk of overall mortality after adjusting for age, sex, prednisolone use, and comorbidities. The cumulative incidence of the overall survival was significantly higher in CHM users. Association rule and network analysis showed that one main CHM cluster was commonly used to treat patients with muscular dystrophies in Taiwan. The cluster includes Yin-Qiao-San, Ban-Xia-Bai-Zhu-Tian-Ma-Tang, Zhi-Ke (Citrus aurantium L.), Yu-Xing-Cao (Houttuynia cordata Thunb.), Che-Qian-Zi (Plantago asiatica L.), and Da-Huang (Rheum palmatum L.). Conclusions Our data suggest that adjunctive therapy with CHM may help to reduce the overall mortality among patients with muscular dystrophies. The identification of the CHM cluster allows us to narrow down the key active compounds and may enable future therapeutic developments and clinical trial designs to improve overall survival in these patients.

Purpose We report the first family with PIGA- associated epileptic encephalopathy in Taiwan and hope to elucidate its special phenotype and inheritance pattern. Method We found a Taiwanese family with several members suffered from severe epileptic encephalopathy (ZY07, ZY01, ZY04). To determine the underlying etiology, whole exome sequencing was conducted. Results A single novel variant, NM_002641: c.356G > A, p.Arg119Gln, was identified in the X chromosome PIGA gene in our proband patient (ZY07). The patient's mother (ZY02) and aunt (ZY03) were confirmed as carriers of the hemizygous variant. Conclusions This paper highlights the highly transmitted features of PIGA and other X-linked EIEEs, raising awareness of rare forms of epileptic encephalopathy.

Background Obesity is one of the main causes of preventable death. Complications of childhood obesity include cardiovascular risk, impaired glucose tolerance, type 2 diabetes mellitus, and acanthosis nigricans (AN; associated with obesity as a manifestation of cutaneous insulin resistance). An interaction between AN and obesity as well as a detailed mechanism for the pre- and co-obesity appearance of AN in children are still to be revealed. Purposes This research tries to assess involvement of the insulin/insulin-like growth factor (IGF) receptor pathway in childhood pre- and co-obesity AN via a study of the association of polymorphisms of the INSR, IRS1, and IGF1R genes with pre- and co-obesity AN. Methods In total, 99 children with pre- and co-obesity AN and 100 healthy controls were genotyped and analyzed by the polymerase chain reaction-restriction fragment length polymorphism method. Results Intergroup frequency differed starkly for INSR His1085His and IGF1R IVS7-20, but not in the IRS1 Ala804Ala or IGF1R Thr766Thr genotypes. The T allele of INSR His1085His and C allele of IGF1R IVS7-20 both conferred a starkly( p=0.04 and 2.84E-6 = 2.84 x 10 −6 , respectively)higher risk for AN. Conclusion The above findings suggest that certain genetic variants in insulin/insulin-like growth factor (IGF) receptor pathway might be correlated with the appearance of AN prior to or concurrent with obesity, and also reveal the insulin/IGF receptor pathway as crucial in pre- and co-obesity AN.

Background: Recent research suggests that Tourette’s syndrome (TS) may result from a defect in the dopamine system. Several candidate gene polymorphisms have been implicated in attention deficit hyperactivity disorder, including the dopamine transporter (DAT1 )a nd dopamine b-hydroxylase (DBH) genes. A high rate of comorbidity between attention deficit hyperactivity disorder and TS indicates that they may share the same pathophysiology. Purpose: We aimed to test the hypothesis that the dopamine gene might play a role in TS. Methods: An association study, using an independent sample of patients from the midland region of Taiwan, was performed to investigate whether DAT1 and DBH gene polymorphisms can be used as markers of susceptibility to TS. A total of 160 children with TS and 83 normal controlparticipantswereincludedinthestudy.Polymerasechainreactionwasusedtoidentify polymorphisms in the DAT1 (40 bp VNTR) and DBH (TaqI A2) genes. Genotypes and allelic frequencies for the DAT1 and DBH gene polymorphisms in both groups were compared. Results: The results showed that genotypes and allelic frequencies in both groups were not significantly different. The most common genotype for DAT1 (40 bp VNTR) was the 10,10 homozygote in both groups. The most common genotype for DBH (TaqI A2) was the T homozygote in both groups. Conclusion: These data suggest that the DAT1 and DBH genes may not be useful markers to predict susceptibility to TS.

Distal 10q deletion syndrome is an uncommon chromosomal disorder. Interstitial deletion involving bands 10q25–10q26.1 is extremely rare and few cases have been reported. The characteristic features are facial dysmorphisms, postnatal growth retardation, developmental delay, congenital heart disease, genitourinary anomalies, digital anomalies, and strabismus. We report for the first time a patient with de novo 10q interstitial deletion del (10)(q26.1q26.3) and cataract.

Tourette syndrome has a multifactorial etiology in which genetic, environmental, and immunologic factors interact to establish vulnerability. Various interleukin 1 genes are associated with several immunoinflammatory diseases. It is not known whether polymorphisms in those genes are involved in the pathogenesis of Tourette syndrome. In this association study, single nucleotide polymorphisms were used to investigate the distribution of genotypes of the interleukin 1 receptor antagonist gene (IL1RN; alias IL1RA) and of the interleukin 1beta gene (IL1B) in patients with Tourette syndrome. A total of 159 children with Tourette syndrome and 175 healthy control subjects were included in the study. There was no significant difference between patients and control subjects in the distribution of genotype and allele frequencies for IL1B exon 5 and promoter region; however, the number of individuals homozygotic for IL1RN( *)1 was significantly greater (P0.0001), and the IL1RN( *)1 allele frequency was significantly higher (P0.0001), among patients than among control subjects. The odds ratio for developing Tourette syndrome in individuals with the IL1RN( *)1 allele, compared with IL1RN( *)2, was 7.65. Thus, the IL1RN gene may be a useful marker for prediction of the susceptibility to Tourette syndrome.

Objective To evaluate growth and neurodevelopmental outcomes in preterm very low birth weight (PVLBW) infants treated with oral probiotics for the prevention of necrotizing enterocolitis (NEC). Study design A prospective follow-up study was performed in a cohort of PVLBW infants enrolled in a single center with a masked randomized control trial to evaluate the efficacy of oral probiotics in preventing NEC. Growth measures included weight, length, and head circumference. Neurologic and sensory performance was evaluated with standard techniques. Psychometric parameters were measured used the Bayley Scales of Infant Development II (BSID-II). The studies were performed at 3 years corrected age. The primary outcome was death or neurodevelopmental impairment. Results Of the 367 subjects enrolled in trial, 301 (89.9%) were evaluated (153 in the probiotics group and 148 in the control group). There were no significant differences in growth or in any of the neurodevelopmental and sensory outcomes between the 2 groups. Conclusions Oral probiotics given to PVLBW infants at 1 week after birth to reduce the incidence of NEC did not affect growth and neurodevelopmental and sensory outcomes at 3 years corrected age.

BackgroundInformation regarding the efficacy of growth hormone (GH) therapy in Asian Prader-Willi syndrome (PWS) patients is lacking. We report our experience with GH treatment in children with PWS in Taiwan.MethodsForty-six PWS patients (27 males, 19 females; age range, 1 year 4 months to 13 years 7 months) who received and/or who are currently receiving GH treatment (0.1 IU/kg/day subcutaneously) for a period from 1 year to 3 years were retro-spectively analyzed. We evaluated height, weight, body mass index (BMI) and Rohrer index, before and after GH treatment.ResultsAfter patients had received GH for 1, 2 and 3 years, a significant improvement in mean height standard deviation score (SDS) was noted from −1.24 to −0.31 (p

Missense mutations in the gamma2 subunit of gamma-aminobutyric acid (GABA) receptor gene have recently been described in families with idiopathic generalized epilepsies. This study aimed to evaluate whether polymorphisms of the gamma2 subunit of the GABA receptor gene are associated with idiopathic generalized epilepsies. A total of 77 children with idiopathic generalized epilepsies and 83 normal control subjects were included in the study. Polymerase chain reaction was used to identify the C/T and A/G polymorphisms of the gamma2 subunit of the GABA receptor gene on chromosome 5q33. Genotypes and allelic frequencies in both groups were compared. The gamma2 subunit of the GABA receptor (nucleotide position 3145 in intron G-A) gene in both groups was not significantly different. In contrast, the gamma2 subunit of GABA receptor (SNP211037)-C allele frequency in patients with idiopathic generalized epilepsies was significantly higher than that in healthy control subjects (P = 0.002). The odds ratio for developing idiopathic generalized epilepsies in individuals with the gamma2 subunit of the GABA receptor (SNP211037)-C/C genotype was 3.61 compared with individuals with the gamma2 subunit of the GABA receptor (SNP211037)-T/T genotype. These data suggest that the gamma2 subunit of the GABA receptor gene might be one of the susceptibility factors for idiopathic generalized epilepsies.

The pathophysiology of Tourette syndrome may involve the dopamine system. Dysfunction of the dopamine receptor D2 gene leads to many neuropsychiatric disorders. The objective of this study is to test the hypothesis that the dopamine receptor D2 gene may play a role in Tourette syndrome. A total of 151 children with Tourette syndrome and 183 normal control subjects were included in the study. Polymerase chain reaction was used to identify the Taq I DRD2 and DRD2 (H313H) polymorphisms of the dopamine receptor D2 gene. The genotype proportions of Taq I DRD2 and DRD2 (H313H) polymorphisms in the two groups were significantly different (P0.01 for both). The odds ratio for developing Tourette syndrome in individuals with the Taq I DRD2 A1 homozygote was 2.253 (95% confidence interval, 1.124-4.517) compared with individuals with the Taq I DRD2 A2 homozygote. The odds ratio for developing Tourette syndrome in individuals with the DRD2 (H313H) C homozygote was 2.96 (95% confidence interval, 1.398-6.269) compared with individuals with DRD2 (H313H) T homozygote. This study has demonstrated an association between the dopamine receptor D2 gene and Tourette syndrome. These data suggest that the dopamine receptor D2 gene or a closely linked gene might be one of the susceptibility factors for Tourette syndrome.

We report the case of a 2-year-old male with congenital symmetric facial diplegia, and bilateral paralysis of abduction of the eyes. Findings were compatible with a diagnosis of Mobius syndrome. Routine G-banded chromosome analysis revealed a mosaic karyotype with 40 cells showing normal 46,XX and 10 cells showing normal 46,XY. An XX male attributed to XX/XY mosaicism was diagnosed. The phenotype of our patient did not coincide with any described form of XX reversal syndrome, but and was a unique combination of both syndromes. The disorder of this patient is likely to represent a genetic condition with pleiotropic effects on brain development and sex determination, providing adding further evidence for the heterogeneity of Mobius syndrome and sex reversal syndromes.

Febrile convulsions (FCs) represent the majority of childhood seizures, and patients have a genetic predisposition to their development. The genetic susceptibility to FCs seems to involve multiple genes in most instances. Recent studies provided evidence that mutations in SCN1A represent the most frequent cause of generalized epilepsy with febrile seizures plus an autosomal-dominant epilepsy syndrome. SCN1A mutations alter channel inactivation, resulting in persistent inward sodium current. It is not known if polymorphisms in those genes involved in familial epilepsies also contribute to the pathogenesis of FCs. By performing an association study, we used single nucleotide polymorphisms to investigate the distribution of genotypes of SCN1A in patients with FCs. A total of 104 Taiwanese children with FCs and 83 normal control subjects were included in the study. Polymerase chain reaction was used to identify the A/G polymorphism of the SCN1A gene. The results showed that genotypes and allelic frequencies for the SCN1A gene polymorphisms in both groups were not significantly different. These data suggest that the SCN1A gene might not be one of the susceptibility factors for FCs. Pure FCs and febrile convulsions associated with idiopathic generalized epilepsy may not share a common genetic etiology.

In encephalopathic infants, cerebrospinal fluid hyperglycinemia and elevated cerebrospinal fluid to plasma glycine ratio are considered pathognomonic of nonketotic hyperglycinemia (NKH). We present a case of NKH complicated by neonatal intractable seizures. Increased ratio of cerebrospinal fluid to plasma glycine concentrations of 0.28 was seen as a strong diagnostic indicator of nonketotic hyperglycinemia. Evaluating sick neonates with hypotonia, encephalopathy, and/or seizures is a diagnostic challenge. NKH should be considered; elevated cerebrospinal fluid/plasma glycine ratio will allow correct identification and treatment more often in the future.

Tourette syndrome is a neurologic disorder characterized by both motor and vocal tics. Recently, two variants, including a single-base deletion resulting in a truncated protein and a 3′-untranslated-region variant altering a binding site for micro-RNA in the Slit and Trk-like 1 gene, were found to be a genetic cause of Tourette syndrome. The Slit and Trk-like 1 family was identified as neuronal transmembrane proteins that control neurite outgrowth. This study aimed to determine whether mutations in the gene can be found in Taiwanese patients with Tourette syndrome. In total, 160 patients were included. All children underwent peripheral blood sampling for genotype analyses. We sequenced the whole Slit and Trk-like 1 gene, including the promoter, the 3′-untranslated region, the 5′-untranslated region, and the whole coding region. We found that none of the 160 samples revealed any mutation in the whole gene sequence. In addition, there was only one polymorphism, c.3225 T>C, detected in 10 individuals. We conclude that in rare variants, it may be difficult to establish an association with disorder. Therefore, genetic screening in the Slit and Trk-like 1 gene for the recently identified mutations does not appear to be of utility in the diagnosis of Tourette syndrome.

Various studies have shown that brain-derived neurotrophic factor (BDNF) increased neuronal excitability. We tested that BDNF might be involved in the etiology of febrile seizures (FSs). A total of 186 Taiwanese children were divided into two groups: (1) FSs (n = 104); (2) normal control subjects (n = 83). A single base pair polymorphism SNP6265 (Val66Met) at position 196 was analyzed. Our findings suggest that the BDNF polymorphisms were not candidate genetic markers.