Chromosomal Microarray Analysis as a First-Tier Clinical Diagnostic Test in Patients With Developmental Delay/Intellectual Disability, Autism Spectrum Disorders, and Multiple Congenital Anomalies: A Prospective Multicenter Study in Korea

BACKGROUND: To validate the clinical application of chromosomal microarray analysis (CMA) as a first-tier clinical diagnostic test and to determine the impact of CMA results on patient clinical management, we conducted a multicenter prospective study in Korean patients diagnosed as having developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), and multiple congenital anomalies (MCA). METHODS: We performed both CMA and G-banding cytogenetics as the first-tier tests in 617 patients. To determine whether the CMA results directly influenced treatment recommendations, the referring clinicians were asked to complete a 39-item questionnaire for each patient separately after receiving the CMA results. RESULTS: A total of 122 patients (19.8%) had abnormal CMA results, with either pathogenic variants (N=65) or variants of possible significance (VPS, N=57). Thirty-five well-known diseases were detected: 16p11.2 microdeletion syndrome was the most common, followed by Prader-Willi syndrome, 15q11-q13 duplication, Down syndrome, and Duchenne muscular dystrophy. Variants of unknown significance (VUS) were discovered in 51 patients (8.3%). VUS of genes putatively associated with developmental disorders were found in five patients: IMMP2L deletion, PTCH1 duplication, and ATRNL1 deletion. CMA results influenced clinical management, such as imaging studies, specialist referral, and laboratory testing in 71.4% of patients overall, and in 86.0%, 83.3%, 75.0%, and 67.3% of patients with VPS, pathogenic variants, VUS, and benign variants, respectively. CONCLUSIONS: Clinical application of CMA as a first-tier test improves diagnostic yields and the quality of clinical management in patients with DD/ID, ASD, and MCA.

Reconsideration of Vigabatrin Effect in Infantile Spasms Treatment / 대한소아신경학회지

PURPOSE@#To investigate the effect of vigabatrin (VGB) as a therapeutic agent for patients with infantile spasms (IS), compare risk factors for treatment response, and review safety of VGB by assessing its side effects.@*METHODS@#Among 35 patients admitted to the Department of Pediatric Neurology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea who received initial monotherapy with VGB under diagnosis of IS, 23 patients who met our inclusion criteria were enrolled and their medical records were retrospectively reviewed.@*RESULTS@#Of these 23 patients, average age at diagnosis was 7.26±4.8 months and average age at spasms was 6.20±3.8 months. Average treatment lag was 1.09±1.8 months. Thirteen patients (56.5%) achieved seizure free status. There was no ophthalmic complication among patients. Remission of hypsarrhythmia at 3 and 6 months after treatment was a good prognostic factor (P=0.026 and P=0.004, respectively).@*CONCLUSION@#VGB is effective enough to become a first-line drug for children with IS. Better prognosis can be expected in patients with clinical remission of hypsarrhythmia on electroencephalography after treatment initiation using VGB compared to those who do not have such remission. Regular eye examination and follow-up check-up are also needed in parallel with the use of VGB.

The Correlation between ADHD and Brain MRI Findings in Children with Epilepsy / 대한소아신경학회지

PURPOSE: We analyze the brain magnetic resonance imaging (MRI) findings of children with epilepsy and concomitant attention deficit hyperactivity disorder (ADHD) to investigate the correlation between brain MRI and ADHD, and to determine whether abnormal MRI finding can be a risk factor for the development of ADHD. METHODS: A total of 55 patients (36 male, 19 female) were diagnosed as ADHD in children with epilepsy at the pediatric neurology department of Seoul St. Mary hospital from March, 2009 to December, 2013. The records of these patients were retrospectively reviewed. RESULTS: 29 patients (52.7%) had normal MRI findings, and 26 patients (47.3%) had abnormal MRI findings. The inattention type of ADHD (96.5%) was the largest type in a group of normal brain MRI findings, but the combined type (53.8%) and the inattention type (46.2%) occupied the majority in a group of abnormal MRI findings. The score of symptom in inattention was 7.44/9 in a group of normal MRI findings, while 8.2/9 in a group of abnormal MRI findings. And the score of symptom in hyperactivity was 2.93/9 in a group of normal MRI findings, while it was 4.8/9 in a group of abnormal MRI findings (P < 0.001). 7 patients (12.7%) revealed hippocampal sclerosis out of 26 abnormal MRI findings, and they had significantly higher scores of ADHD symptoms (8.57/9, 4.8/9) compared to normal group (7.83/9, 4.23/9). CONCLUSION: Abnormal MRI findings in children with epilepsy are not only closely related to ADHD but may also be associated with the severity of ADHD.

Effects of Anticonvulsant Monotherapy on Bone Mineral Density in Children / 대한소아신경학회지

PURPOSE: The use of anticonvulsants can cause side effects such as reduction of bone mineral density, requiring attention in growing children. The aim of our study is to investigate the effects of different anticonvulsants on bone mineral density in epileptic patients treated with monotherapy. METHODS: We retrospectively reviewed medical records of 60 subjects who visited the Pediatric Epilepsy Clinic of Bucheon St. Mary's Hospital from January 2013 to December 2017. Bone mineral density was measured with dual photon absorptiometry every 6 months. RESULTS: The number of patients treated with oxcarbazepine, valproate and levetiracetam was 31, 16 and 13, respectively. Reduction of bone mineral density was seen in 8 out of 31 patients (25.8%, P=0.10) treated with oxcarbazepine, 9 out of 16 patients treated with valproate (56.3%, P=0.04) and 4 out of 13 patients treated with levetiracetam (30.8%, P=0.50). CONCLUSION: There was a significant reduction of bone mineral density in patients treated with valproate compared to the other anticonvulsants in our study. We believe attention to bone mineral density is required in children treated with anticonvulsants.

Clinical Usefulness of Aripiprazole and Lamotrigine in Schizoaffective Presentation of Tuberous Sclerosis

Tuberous sclerosis is not as rare as once thought and has high psychiatric comorbidities. However, bipolar or psychotic features associated with tuberous sclerosis have been rarely reported. This report first presents a tuberous sclerosis patient, resembling a schizoaffective disorder of bipolar type. A patient with known tuberous sclerosis displayed mood fluctuation and psychotic features. Her symptoms did not remit along with several psychiatric medications. After hospitalization, the patient responded well with lamotrigine and aripiprazole without exacerbation. As demonstrated in this case, tuberous sclerosis may also encompass bipolar affective or psychotic features. We would like to point out the necessity to consider bipolarity in evaluating and treating tuberous sclerosis.

Neurocognitive Outcome in Survivors of Childhood Acute Lymphoblastic Leukemia: Experience at a Tertiary Care Hospital in Korea

This study was conducted to investigate long-term neurocognitive outcomes and to determine associated risk factors in a cohort of Korean survivors of childhood acute lymphoblastic leukemia (ALL). Forty-two survivors of ALL were compared with 42 healthy controls on measures of a neurocognitive test battery. We analysed potential risk factors (cranial irradiation, sex, age at diagnosis, elapsed time from diagnosis, and ALL risk group) on neurocognitive outcomes. ALL patients had lower, but non-significant full-scale intelligence quotient (FSIQ, 107.2 +/- 12.2 vs. 111.7 +/- 10.2), verbal intelligence quotient (VIQ, 107.7 +/- 13.6 vs. 112.2 +/- 11.4), and performance intelligence quotient (PIQ, 106.3 +/- 14.2 vs. 110.1 +/- 10.7) scores than healthy controls. However, patients treated with cranial irradiation performed significantly lower on FSIQ (102.2 +/- 8.1), VIQ (103.3 +/- 11.7), and PIQ (101.4 +/- 13.2) compared to non-irradiated patients and healthy controls. ALL patients also had poor attention, concentration, and executive functions. Among ALL survivors, cranial irradiation was a risk factor for poor FSIQ, being male was a risk factor for poor PIQ, and younger age was a risk factor for poor attention. Therefore, the delayed cognitive effects of ALL treatment and its impact on quality of life require continuing monitoring and management.

Clinical Characteristics of Attention Deficit Hyperactivity Disorder in Childhood Malignant Hematologic Diseases / 대한소아신경학회지

PURPOSE: The purpose of this study is to identify the prevalence of attention-deficit hyperactivity disorder (ADHD) among children treated for childhood malignant hematologic diseases, and determine the different characteristics of the patients with ADHD as opposed to the patients without ADHD, which will help to predict the development of ADHD and to help treat them. METHODS: 172 patients diagnosed as childhood malignant hematologic diseases went through the test battery including diagnostic criteria for ADHD in pediatric neurology department of Seoul St. Mary's hospital from March 2009 to May 2012. Age, sex, ADHD type, hematologic diseases type, age at onset of hematologic diseases, treatment with/without chemotherapy and relapse were investigated. These data were compared between the groups of the patients without ADHD and with ADHD. RESULTS: Out of 172 patients, Fifty one patients (29.6%) had both ADHD and childhood malignant hematologic diseases. Sex (male), age at onset of hematologic diseases ( or =11 years (P=0.007). The patients with chemotherapy had about 3.4 fold increased risk for ADHD compared to the patients without chemotherapy (P=0.023). CONCLUSION: This study showed childhood malignant hematologic disorders has significant correlation with ADHD. In addition, Male, < or =5 years of age at onset and use of chemotherapy in the patients can be necessary to predict ADHD. Therefore, early detection and establishment of the countermeasures for ADHD are necessary.

Outcomes of the Monoconversion to Valproate or Lamotrigine for Absence Seizures / 대한소아신경학회지

PURPOSE: Ethosuximide (ESX) is currently not available due to various reasons in Korea. The aim of this study is to compare the efficacy of valproate (VPA) and lamotrigine (LTG) when ESX monotherapy was replaced by VPA or LTG. METHODS: A retrospective study was done for a total of 34 patients treated with ESX in 5 different hospitals affiliated with Catholic University of Korea from January, 2010 to December, 2012. They all were initially treated with ESX, but later switched to VPA or LTG. The subjects were selected based on clinical symptoms and electroencephalography findings. RESULTS: Among 34 patients, VPA was prescribed to 17 patients (50.0%) and LTG to 17 patients (50.0%). Twenty patients (58.8%) achieved the seizure freedom after 3 months of the treatments, 13 patients (76.5%) by VPA and 7 (41.2%) by LTG respectively. Four patients (23.5%) with VPA and 10 (58.8%) with LTG were replaced by other anticonvulsants due to ineffectiveness and/or side effects of medication. When we compare the efficacy of seizure reduction between VPA and LTG after 3 month period of the treatment, the efficacy of VPA was better than that of LTG (P=0.04). CONCLUSION: The results of this study suggest that the VPA is a better alternative anticonvulsant than LTG for the patients with absence epilepsy who are unable to continue ESX.

Neonatal Meningoencephalitis caused by Herpes Simplex Virus Type 2 / 소아감염

Despite its rare occurrence, early diagnosis and appropriate treatment for neonatal herpes simplex virus infection are mandatory due to its high morbidity and mortality. In Korea, there has been no epidemiologic data on neonatal herpes simplex virus infection, and even case reports are rare. We observed a 16-day-old neonate who presented with fever and seizures. We diagnosed her with meningoencephalitis caused by herpes simplex virus type 2 based on the polymerase chain reaction test, and treated her with intravenous acyclovir and anticonvulsants. The seroprevalence of herpes simplex virus type 2 sharply increases in women in their 30s, and the average age for childbirth has increased to older than 30 years of age in Korea; we therefore expect that the incidence of neonatal herpes simplex virus type 2 infection will rise in Korea, and more attention should be directed to neonatal herpes simplex virus type 2 infection. We report this newborn patient's case along with a literature review.

The Impact of Anticonvulsants on Neurologic Outcomes in Neonatal Seizures / 대한주산의학회잡지

PURPOSE: Although neonatal seizures can cause epilepsy, neurodevelopmental disability, and mortality with high frequency, the use of anti-epileptic drug is limited and the side effect of the drug is unidentified. Thus, authors investigated the prognosis of the neonatal seizures related with anti-epileptic drugs and electroencephalography. METHODS: Retrospective medical records of 37 infants with neonatal seizures under 44 weeks of gestational age who were hospitalized at neonatal intensive care unit in Seoul St. Mary' Hospital from January to June 2012 were analyzed. RESULT: The mean gestational age was 32.5+/-1.9 weeks and the mean birth weight was 2,010+/-82 g. Seizures occurred in 65% in infants within 7 days of birth and subtle seizures were most common type. Hypoxic ischemic encephalopathy was the most common cause of seizures and 62% showed abnormal electrographic findings. Among 37 of patients, seizures of 57% were able to be controlled by levetiracetam, but 19% were controlled by co-administration of more than three anti-epileptic drugs. After 6 months of treatment, epilepsy was diagnosed in 6% and developmental delay occurred in 19% among patients controlled by one anti-epileptic drug. Epilepsy and developmental delay occurred in 29% and 86%, respectively, among patients with more than three anti-epileptic drugs. In addition 86% of patients with normal electroencephalographic findings show normal development, but 3 patients with severe abnormalities showed abnormal development. CONCLUSION: Neurologic outcome was not good when the number of anti-epileptic drugs were added due to uncontrolled seizures, and the result of electroencephalography showed severe abnormalities.

Articulation error of children with adenoid hypertrophy / 소아과

PURPOSE: Adenoid hypertrophy is a physical alteration that may affect speech, and a speech disorder can have other negative effects on a child's life. Airway obstruction leads to constricted oral breathing and causes postural alterations of several oro-facial structures, including the mouth, tongue, and hyoid bone. The postural modifications may affect several aspects of speech production. METHODS: In this study, we compared articulation errors in 19 children with adenoid hypertrophy (subject group) to those of 33 children with functional articulation disorders independent of anatomical problems (control group). RESULTS: The mean age of the subject group was significantly higher (P=0.016). Substitution was more frequent in the subject group (P=0.003; odds ratio [OR], 1.80; 95% confidence interval [CI], 1.23-2.62), while omission was less frequent (P<0.001; OR, 0.43; 95% CI, 0.27-0.67). Articulation errors were significantly less frequent in the palatal affricative in the subject group (P=0.047; OR, 0.25; 95% CI, 0.07-0.92). The number of articulation errors in other consonants was not different between the two groups. Nasalization and aspiration were significantly more frequent in the subject group (P=0.007 and 0.014; OR, 14.77 and 0.014; 95% CI, [1.62-135.04] and NA, respectively). Otherwise, there were no differences between the two groups. CONCLUSION: We identified the characteristics of articulation errors in children with adenoid hypertrophy, but our data did not show the relationship between adenoid hypertrophy and oral motor function that has been observed in previous studies. The association between adenoid hypertrophy and oral motor function remains doubtful.

Characteristics of Children with Epilepsy and Concomitant Attention-Deficit Hyperactivity Disorder / 대한소아신경학회지

PURPOSE: To investigate the prevalence of ADHD (attention-deficit hyperactivity disorder) in children with epilepsy and to determine the difference of characteristics in patients with epilepsy and concomitant ADHD as opposed to the patients without ADHD for better management. METHODS: We retrospectively reviewed 184 patients diagnosed as epilepsy and treated with antiepileptic drugs in pediatric neurology department of Seoul St. Mary's hospital from March, 2009 to May, 2012. Their ages ranged from 6 to 18 years. The subjects were included in the study those who made a regular visit for more than a year. RESULTS: 1) Out of 184 patients, 69 patients (37.5%) had both ADHD and epilepsy. 2) In epilepsy children with ADHD, male outnumbered female by almost two fold (male 67: female 33) (P=0.022). 3) In epilepsy children with ADHD, epileptiform discharges on EEG was focused in central regions in 39% of them (P=0.014). 4) In 56% of patients without ADHD, their seizures remained under the control with single anticonvulsant, as opposed to 36% of patients with both ADHD and epilepsy (P=0.001). Therefore, the presence of ADHD in patients with epilepsy might be related to the therapeutic response to anticonvulsants, and be a useful predictive factor for the response to early treatment. CONCLUSION: Patients with epilepsy and concomitant ADHD showed a significant difference and poor response to epilepsy treatment, as opposed to patients without ADHD. Therefore, early detection and establishment of countermeasures for ADHD is necessary.

The role of cytokines in seizures: interleukin (IL)-1beta, IL-1Ra, IL-8, and IL-10 / 소아과

Brain insults, including neurotrauma, infection, and perinatal injuries such as hypoxic ischemic encephalopathy, generate inflammation in the brain. These inflammatory cascades induce a wide spectrum of cytokines, which can cause neuron degeneration, have neurotoxic effects on brain tissue, and lead to the development of seizures, even if they are subclinical and occur at birth. Cytokines are secreted by the glial cells of the central nervous system and they function as immune system mediators. Cytokines can be proinflammatory or anti-inflammatory. Interleukin (IL)-1beta and IL-8 are proinflammatory cytokines that activate additional cytokine cascades and increase seizure susceptibility and organ damage, whereas IL-1 receptor antagonist and IL-10 act as anti-inflammatory cytokines that have protective and anticonvulsant effects. Therefore, the immune system and its associated inflammatory reactions appear to play an important role in brain damage. Whether cytokine release is relevant for the processes of epileptogenesis and antiepileptogenesis, and whether epileptogenesis could be prevented by immunomodulatory treatment should be addressed in future clinical studies. Furthermore, early detection of brain damage and early intervention are essential for the prevention of disease progression and further neurological complications. Therefore, cytokines might be useful as biomarkers for earlier detection of brain damage in high-risk infants.

Clinical Aspects of Children with Developmental Stuttering / 대한소아신경학회지

PURPOSE: The purpose of this study was to evaluate the clinical characteristics of developmental stuttering. METHODS: We retrospectively reviewed 28 children diagnosed with developmental stuttering from January 2001 to December 2010 who had been admitted to the Uijeongbu St. Mary's Hospital. RESULTS: We observed a strong male predominance. The M:F ratio was 13:1 in this study. And the onset age converged on 2-5 years (71.4%). Seven patients (25%) had a family history of language disorders. Among them, 5 cases (17.8%) was about to developmental stuttering. As for associated disorders, 5 patients (17.8%) had another language disorder as articulation disorder or developmental language delay; respectively 4 patients (14.2%) and 1 patient (3.6%). Three patients (10.7%) had psychologic disorder as ADHD or anxiety disorder; respectively 2 patients (7.1%) and 1 patient (3.6%). In addition, 2 patients (7.1%) had ankyloglossia including 1 case accompanying with articulation disorder. Another 2 patients (7.1%) had adenoid-hypertrophy also including 1 case accompanying with articulation disorder. The proportion of moderate-to-severe and severe cases was 63.6%. And we observed remarkable improvement of stuttering in 92.9% (13/14) patients during repetitive speech or text reading. CONCLUSION: Several distinctive characteristics of developmental stuttering were observed in this study. The value of this study is that it's the clinical report on developmental stuttering by pediatrician and we expect this study will contribute to the basis of forward investigation.

Neonatal Seizures in Preterm Infants / 대한소아신경학회지

PURPOSE: Neonatal seizures are the most prominent feature of neonatal neurologic dysfunction, and the lifespan risk for seizures is highest in the neonatal period, especially in preterm infants. This study was aimed to find and analyze the risk factors and clinical profiles of seizures in preterm infants. METHODS: Sixteen cases of preterms with seizures were retrospectively reviewed between Mar. 2009 and Feb. 2012. RESULTS: The average gestational age was 30.3+/-4.1 weeks and 11 patients (68.7%) experienced seizures within 1 week after the birth. Eight cases (50%) had a perinatal asphyxia during the delivery and 7 cases (43.8%) had a history of perinatal maternal illness. Various types of seizures were observed of which subtle seizures were the most common (50%). Electroecephalographies were performed in 12 cases, which showed abnormal findings in 9 cases (75%). Neuroimaging studies were performed in 16 cases and showed abnormal findings in 10 cases (62.5%). Thirteen patients were discharged in the improved state and 3 patients expired. Eight cases had normal outcome, while 3 cases showed developmental delay. Prognosis was unknown in 2 cases due to follow up loss. CONCLUSION: Neonatal asphyxia is the most important risk factor. Furthermore, infants with a history of perinatal maternal illness appear to be at risk for neonatal seizures. EEG is a sensitive method for assessing seizure activity and prognosis. Monitoring high risk infants with asphyxia and a history of perinatal maternal illness, and early postnatal tracing with EEG is required to detect and manage high risk preterms.

Effects of Topiramate on Body Weight and Serum Levels of Insulin and Leptin in Young Rats Fed a High Fat Diet / 대한소아신경학회지

PURPOSE: Topiramate is an antiepileptic drug used widely in the treatment of epilepsy. It has also been reported to reduce body weight in humans and is currently used for eating disorders and obesity; little is known about the mechanism by which this drug induces weight loss. This study was carried out to investigate the effects of topiramate on weight and serum levels of insulin and leptin in young rats fed high fat diet (HFD). METHODS: Forty male Wistar rats (4 weeks old) were randomly divided into four groups (diet, regular diet and high fat diet, treatment, topiramate and placebo). Topiramate (50 mg/kg/day) was orally administered via gastric gavage twice a day for 4 weeks. Food intake and body weight were monitored throughout the study. After 4 weeks, the plasma levels of glucose, triglycerides, free fatty acids, leptin, and insulin were determined. RESULTS: We found significant reduction in body weight gain after topiramate administration in the HFD group (topiramate, 351.6 +/- 28.6g; placebo, 397.6 +/- 28.4g) (P<0.05). Topiramate was able to reduce food intake in both diet groups (P<0.05). Furture, fasting glucose levels were significantly lower in both topiramate groups than placebo groups (P<0.05), and serum leptin levels in the HFD group were decreased (P<0.05). Additionally, there was no significant difference in serum levels of triglycerides, free fatty acids, or insulin between the four groups. CONCLUSION: Topiramate significantly inhibited body weight gain by reducing food intake, especially in the HFD group and reduced serum levels of glucose in both diet groups and of leptin in the HFD group.

A Case of Walker-Warburg Syndrome Presented with Seizures / 대한소아신경학회지

Walker-Warburg syndrome (WWS) is a rare autosomal recessive disorder characterized by congenital muscular dystrophy, brain (lissencephaly, hydrocephalus, cerebellar malformations) and retinal abnormalities, and is associated with mental retardation and seizures. In 1942, Walker was the first to report a case of WWS. As Fukuyama congenital muscular dystrophy or muscle-eye-brain disorder, it has been demonstrated that the glycosylation defects of alpha-dystroglycan which take a great role in muscle and neuron regeneration are at the root of these disorders. We report a five months old male patient who was presented with seizures as the chief complaint and was diagnosed with WWS, based on clinical criteria, MRI, muscular biopsy, ocular examination, and laboratory findings.

Clinical Manifestation of Primary Headache with Epigastric Pain or Tenderness in Children / 대한소아신경학회지

PURPOSE: Population-based studies have shown positive associations between migraine and irritable bowel syndrome, colitis and peptic ulcer and migraine prevalence was higher among patients with dysmotility-like dyspepsia or nausea/vomiting. The aim of this study was to investigate clinical manifestation between primary headache with epigastric pain or tenderness(EPT) and primary headache without EPT. METHODS: We retrospectively reviewed the medical records of 58 patients who were diagnosed primary headache[by ICHD-II(2004)] at Incheon St. Mary Hospital from January, 2006 to December, 2007. Their clinical characteristics such as age, sex, frequency & severity of headache and associated symptoms & signs were analysed. RESULTS: The rate of headache associated with EPT were 36% of migraine cases, 50% of tension-type headache cases, and 100% of unclassified headache cases. Headache with EPT were at a high rate in female. Headache with EPT were more severe than one without EPT. Regulation of behavior, diet and sleep pattern had improved severity of headache in 71% of migraine without EPT and 94% of tension-type headache without EPT, but in 12% of migraine with EPT and 18% of tension-type headache with EPT. Headache disappeared in 64% of migraine with EPT and 53% of tension-type headache by additional regular antiacid medication. CONCLUSION: Our study supports any specific correlation between headache and EPT, but further studies are needed.

Clinical Aspects of Functional Articulation Disorder / 대한소아신경학회지

PURPOSE: Speech and language development is an useful indicator of the overall development of children. Since speech and language delay can lead to emotional, social, and learning problems, the early intervention is very important. We examined 137 children with speech or language problems including 22 children of functional articulation disorders of their clinical features. METHODS: 137 children with speech or language problems in the Department of Pediatrics, Uijeongbu St. Mary's Hospital from January 2004 to December 2007 were reviewed for sex, age, developmental and language test findings retrospectively. Especially, in 22 children diagnosed with functional articulation disorders, articulation test findings were analyzed. RESULTS: 1) The mean age of 137 children was 46.8 months, the ratio of male to female was 2.5:1, and the most frequent age group was 24-35 months. The chief complaints included language delay(67.2%), mispronouncing speech sound(27%), stuttering(3.6%), learning disability(2.2%). The diagnoses of them were developmental language disorder(70.8%), functional articulation disorders(16.1%), mental retardation(5.8%), stuttering(2.9%), tongue tie(0.7%), normal language pattern(3.6%). 2) The mean age of 22 patients with functional articulation disorders was 63 months, the ratio of male to female was 1.4:1, and the most frequent age group was 60-71 months. The mean percentage of consonant correct of Picture Consonant Articulation Test was higher in older age group. In the types of phonetic errors substitutions were most common. Distortions, omissions, and additions were followed in the order of frequency. Substitutions and distortions were common in word initial and medial but omissions in word final. It is appeared that the patients had the difficulties in pronouncing alveolar fricative, palatal affricate, liquid, and velar plosive which mature lately in older children. Mainly palatal affricate, alveolar fricative, and velar plosive were substituted for alveolar plosive and the liquid and alveolar fricative were distorted as gliding. CONCLUSION: Categorizing the cause of language and speech delay is essential to make an adequate treatment plans and decrease the late complications. The future studies for the early screening, more suitable tests in Korean, treatment guidelines or prognosis are needed.

Brain-derived Neurotrophic Factor(BDNF) SNP 6265 Polymorphisms in Febrile Seizure and GEFS+ / 대한소아신경학회지

PURPOSE: Febrile seizure(FS) is one of the most common neurological conditions during childhood, but the pathogenesis of FS remains ambiguous. Various studies have shown that brain-derived neurotrophic factor(BDNF) increased neuronal excitability. In this study, to determine whether the polymorphisms of SNP 6265 within the gene encoding BDNF are associated with susceptibility to FS, the frequencies of the polymorphisms were investigated in children with FS and control subjects. In addition, we analyzed the SNP 6265 polymorphisms in Generalized epilepsy with febrile seizures plus (GEFS+) that hasn't been studied as yet in Korea. METHODS: A total of 79 children selected throughout a collaborative study of Catholic Child Neurology Research Group were divided into three groups: (1) FS(n=30); (2) GEFS+ (n=19); (3) control subjects(n=30). Genotypes and allelic frequencies for the polymorphisms of SNP 6265 located at nucleotide 196 was analyzed and compared among the groups. RESULTS: In this study, proportions for A homozygote, A/G heterozygote and G homozygote for BDNF were as follows: in FS, 46.7%, 36.7% and 16.7%, in GEFS+, 26.3%, 47.4% and 26.3% and in control subjects, 60.0%, 16.7% and 23.3%. The allele A and G frequencies for BDNF in FS were 65.0% and 35.0%, in GEFS+ were 50% and 50%, and in control subjects were 68.3% and 31.7%. However, these differences in genotype proportions and allele frequencies among three groups were not significant. CONCLUSION: These results suggest that genomic variations of BDNF might not be the susceptibility factor for FS and GEFS+ in Korean population.