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1.
Article in English | WPRIM | ID: wpr-899326

ABSTRACT

Primary cilium has a signal transduction function that is essential for brain development, and also determines cell polarity and acts as a mediator for important signaling systems, especially the Sonic Hedgehog (SHH) pathway. TBC1D32 is a ciliary protein, implicated in SHH signaling. Biallelic mutations in the TBC1D32 gene causes a kind of ciliopathy, heterogeneous developmental or degenerative disorders that affect multiple organs, including the brain. Here we report a boy who carried compound heterozygous variants in TBC1D32. The patient showed hypotonia, respiratory difficulty, and multiple anomalies at his birth. He was diagnosed with congenital hypopituitarism and treated with T4, hydrocortisone, and growth hormone. Despite the hormonal replacement, the patient needed long-term respiratory support with tracheostomy and nutritional support with a feeding tube. His developmental milestones were severely retarded. Hydrocephalus and strabismus developed and both required surgery, during the outpatient follow-up. Whole-exome sequencing indicated compound heterozygous variants, c.2200C>T (p.Arg734*) and c.156-1G>T, in TBC1D32 gene. This is the first Korean case of TBC1D32-related ciliopathy and we reported detailed and sequential clinical features. This case demonstrated the utility of whole-exome sequencing and provided valuable clinical data on ultra-rare disease.

2.
Article in English | WPRIM | ID: wpr-891622

ABSTRACT

Primary cilium has a signal transduction function that is essential for brain development, and also determines cell polarity and acts as a mediator for important signaling systems, especially the Sonic Hedgehog (SHH) pathway. TBC1D32 is a ciliary protein, implicated in SHH signaling. Biallelic mutations in the TBC1D32 gene causes a kind of ciliopathy, heterogeneous developmental or degenerative disorders that affect multiple organs, including the brain. Here we report a boy who carried compound heterozygous variants in TBC1D32. The patient showed hypotonia, respiratory difficulty, and multiple anomalies at his birth. He was diagnosed with congenital hypopituitarism and treated with T4, hydrocortisone, and growth hormone. Despite the hormonal replacement, the patient needed long-term respiratory support with tracheostomy and nutritional support with a feeding tube. His developmental milestones were severely retarded. Hydrocephalus and strabismus developed and both required surgery, during the outpatient follow-up. Whole-exome sequencing indicated compound heterozygous variants, c.2200C>T (p.Arg734*) and c.156-1G>T, in TBC1D32 gene. This is the first Korean case of TBC1D32-related ciliopathy and we reported detailed and sequential clinical features. This case demonstrated the utility of whole-exome sequencing and provided valuable clinical data on ultra-rare disease.

5.
Article | WPRIM | ID: wpr-833631

ABSTRACT

Background@#and Purpose: The myelin oligodendrocyte glycoprotein (MOG) antibody is detected at a high rate in childhood acquired demyelinating syndrome (ADS). This study aimed to determine the diagnostic value of the MOG antibody in ADS and the spectrum of MOGantibody-positive demyelinating diseases in children. @*Methods@#This study included 128 patients diagnosed with ADS (n=94) or unexplained encephalitis (n=34). The MOG antibody in serum was tested using an in-house live-cell-based immunofluorescence assay. @*Results@#The MOG antibody was detected in 48 patients (46 ADS patients and 2 encephalitis patients, comprising 23 males and 25 females). Acute disseminated encephalomyelitis (ADEM) (35.4%) was the most-common diagnosis, followed by the unclassified form (17.4%), isolated optic neuritis (ON) (15.2%), neuromyelitis optica spectrum disorder (13.0%), multiple sclerosis (MS) (10.8%), other clinically isolated syndromes [monophasic event except ADEM, isolated ON, or transverse myelitis (TM)] (8.7%), and unexplained encephalitis (4.3%). At the initial presentation, 35 out of the 46 patients with ADS had brain lesions detected in magnetic resonance imaging, and 54% of these 35 patients had encephalopathy. Nine of the 11 patients without brain lesions exhibited only ON. Thirty-nine percent of the patients experienced a multiphasic event during the mean follow-up period of 34.9 months (range 1.4–169.0 months). Encephalopathy at the initial presentation was frequently confirmed in the monophasic group (p= 0.011). @*Conclusions@#MOG antibodies were identified in all pediatric ADS phenotypes except for monophasic TM. Therefore, the MOG antibody test is recommended for all pediatric patients with ADS, especially before a diagnosis of MS and for patients without a clear diagnosis.

6.
Article | WPRIM | ID: wpr-835774

ABSTRACT

The Shprintzen–Goldberg syndrome (SGS) is an extremely rare genetic disorder caused by heterozygous variant in SKI . SGS is characterized by neurodevelopmental impairment with skeletal anomaly. Recognition of SGS is sometimes quite challenging in practice because it has diverse clinical features involving skeletal, neurological, and cardiovascular system. Here we report a case of a 6-month-old boy who initially presented with developmental delay and marfanoid facial features including prominent forehead, hypertelorism, high arched palate and retrognathia. He showed motor developmental delay since birth and could not control his head at the time of first evaluation. His height was above 2 standard deviation score. Arachnodactyly, hypermobility of joints, skin laxity, and pectus excavatum were also noted. Sequencing for FBN1 was negative, however, a novel missense variant, c.350G>A in SKI was identified by sequential whole exome sequencing. To our knowledge, this is the first case with SGS with phenotypic features of SGS overlapping with those of the Marfan syndrome, diagnosed by next generation sequencing in Korea.

7.
Article in English | WPRIM | ID: wpr-915018

ABSTRACT

PURPOSE@#Genetic defects in the nuclear-encoded mitochondrial aminoacyl-tRNA synthetases were first identified as causes of various disorders in 2007. Variants in IARS2, which encodes a mitochondrial isoleucyl-tRNA synthetase, were first reported in 2014. These variants are associated with diverse phenotypes ranging from CAGSSS (CAtaracts, Growth hormone deficiency, Sensory neuropathy, Sensorineural hearing loss, and Skeletal dysplasia) and Leigh syndrome to isolated nonsyndromic cataracts. Here, we describe the phenotypic and genetic spectrum of Korean patients with IARS2-related disorders.@*MATERIALS AND METHODS@#Using whole-exome sequencing followed by Sanger sequencing, we identified five patients with IARS2 mutations. Their medical records and brain magnetic resonance images were reviewed retrospectively.@*RESULTS@#All five patients presented with developmental delay or regression before 18 months of age. Three patients had bilateral cataracts, but none had hearing loss or sensory neuropathy. No evidence of skeletal dysplasia was noted, but two had short stature. One patient had cardiomyopathy and another exhibited renal tubulopathy and hypoparathyroidism. Their brain imaging findings were consistent with Leigh syndrome. Interestingly, we found the recurrent mutations p.R817H and p.V105Dfs*7 in IARS2.@*CONCLUSION@#To our knowledge, this is the first report of Korean patients with IARS2-related disorders. Our findings broaden the phenotypic and genotypic spectrum of IARS2-related disorders in Korea and will help to increase clinical awareness of IARS2-related neurodegenerative diseases.

8.
Article in English | WPRIM | ID: wpr-915016

ABSTRACT

Limb-girdle muscular dystrophy (LGMD) is a group of muscular dystrophies that has extremely heterogeneous clinical features and genetic background. The caveolin-3 gene (CAV3) is one of the causative genes. LGMD appears as a clinical continuum, from isolated skeletal muscle involvement to long QT syndrome. Here we report two patients without apparent muscle weakness in a family with CAV3 mutation.A 7-month-old Korean boy visited our muscle clinic because of an incidental finding of elevated serum creatine kinase (CK) concentration (680 IU/L, reference range, 20-270 IU/L) without clinical symptoms. The patient was born after an uneventful pregnancy and showed normal developmental milestones. He developed pseudohypertrophy of his calf muscle during the follow-up. We obtained a muscle biopsy at age 14 months, which showed size variations and degenerating/regenerating myofibers with endomysial fibrosis and immunohistochemical evidence of normal dystrophin. Under the impression of LGMD, we performed target panel sequencing and identified a heterozygous in-frame mutation of CAV3, c.307_312delGTGGTG (p.Val103_Val104del). Immunohistochemical staining of muscle indicated complete loss of caveolin-3 compared with normal control muscle, which supported the variant's pathogenicity. We performed segregation analysis and found that the patient's mother had the same variant with elevated serum CK level (972 IU/L).We report on autosomal dominant familial caveolinopathy caused by a pathogenic variant in CAV3, which was asymptomatic until the fourth decade. This case highlights the utility of next generation sequencing in the diagnosis of muscular dystrophies and the additive role of muscle biopsy to confirm the variants.

9.
Yonsei Medical Journal ; : 1209-1215, 2019.
Article in English | WPRIM | ID: wpr-762062

ABSTRACT

GLUT1 deficiency is a rare neurometabolic disorder that can be effectively treated with ketogenic diet. However, this condition is underdiagnosed due to its nonspecific, overlapping, and evolving symptoms with age. We retrospectively reviewed the clinical course of nine patients diagnosed with GLUT1 deficiency, based on SLC2A1 mutations and/or glucose concentration in cerebrospinal fluid. The patients included eight boys and one girl who initially presented with seizures (44%, 4/9) or delayed development (44%, 4/9) before 2 years of age, except for one patient who presented with apnea as a neonate. Over the clinical course, all of the children developed seizures of the mixed type, including absence seizures and generalized tonic–clonic seizures. About half (56%, 5/9) showed movement disorders such as ataxia, dystonia, or dyskinesia. We observed an evolution of phenotype over time, although this was not uniform across all patients. Only one child had microcephaly. In five patients, ketogenic diet was effective in reducing seizures and movement symptoms, and the patients exhibited subjective improvement in cognitive function. Diagnosing GLUT1 deficiency can be challenging due to the phenotypic variability and evolution. A high index of clinical suspicion in pediatric and even older patients with epilepsy or movement disorders is key to the early diagnosis and treatment, which can improve the patient's quality of life.


Subject(s)
Apnea , Ataxia , Cerebrospinal Fluid , Child , Clothing , Cognition , Dyskinesias , Dystonia , Early Diagnosis , Epilepsy , Epilepsy, Absence , Female , Glucose , Humans , Infant, Newborn , Diet, Ketogenic , Microcephaly , Movement Disorders , Phenotype , Quality of Life , Retrospective Studies , Seizures
10.
Article in English | WPRIM | ID: wpr-765348

ABSTRACT

Focal cortical dysplasia (FCD) is the major cause of intractable focal epilepsy in childhood leading to epilepsy surgery. The overall seizure freedom after surgery ranges between 50–75% at 2 years after surgery and the long-term seizure freedom remain relatively stable. Seizure outcome after surgery depends on a various factors such as pathologic etiologies, extent of lesion, and types of surgery. Therefore, seizure outcome after surgery for FCD should be analyzed carefully considering cohorts' characteristics. Studies of pediatric epilepsy surgery emphasize the early surgical intervention for a better cognition. Early surgical intervention and cessation of seizure activity are important for children with intractable epilepsy. However, there are limited data on the cognitive outcome after surgery in pediatric FCD, requiring further investigation. This paper reviews the seizure and cognitive outcomes of epilepsy surgery for FCD in children. Several prognostic factors influencing seizure outcome after surgery will be discussed in detail.


Subject(s)
Child , Cognition , Drug Resistant Epilepsy , Epilepsies, Partial , Epilepsy , Freedom , Humans , Malformations of Cortical Development , Patient Outcome Assessment , Pediatrics , Seizures
11.
Article in English | WPRIM | ID: wpr-764367

ABSTRACT

BACKGROUND AND PURPOSE: To identify whether serum uric acid levels are significantly higher in patients with benign convulsion associated with mild gastroenteritis (CwG) than in patients with acute gastroenteritis. METHODS: This retrospective study compared the serum levels of uric acid between CwG, acute gastroenteritis, and febrile seizure after correcting for the varying degree of mild dehydration using serum HCO3⁻ levels. We also compared the serum uric acid levels between patients with CwG and febrile seizures in order to exclude the effect of seizures on uric acid. RESULTS: This study included 154 CwG patients (age range 0.73–3.19 years), 2,938 patients with acute gastroenteritis, and 154 patients with febrile seizure. The serum uric acid level was significantly higher in CwG patients than in patients with acute gastroenteritis [9.79±2.16 mg/dL vs. 6.04±2.3 mg/dL (mean±SD), p<0.001]. This difference was also significant after correcting for dehydration. The serum uric acid level was significantly higher in CwG patients than in dehydration-corrected acute gastroenteritis patients (9.79±2.16 mg/dL vs. 6.67±2.48 mg/dL, p<0.001). The serum uric acid level was not elevated in patients with febrile seizure. CONCLUSIONS: We have confirmed that serum uric acid is elevated in CwG patients even after correcting for their dehydration status, and that this was not a postictal phenomenon. Highly elevated serum uric acid in CwG could be a useful clinical indicator of CwG in patients with acute gastroenteritis.


Subject(s)
Child , Dehydration , Gastroenteritis , Humans , Retrospective Studies , Seizures , Seizures, Febrile , Uric Acid
12.
Article in English | WPRIM | ID: wpr-764360

ABSTRACT

BACKGROUND AND PURPOSE: Febrile seizure (FS) is a unique type of seizure that only occurs during childhood. Genelized epilepsy with febrile seizure plus (GEFS+) is a familial epilepsy syndrome associated with FS and afebrile seizure (AFS). Both seizure types are related to fever, but whether genetic susceptibility to inflammation is implicated in them is still unclear. To analyze the associations between postictal serum cytokine levels and genetic variants in the cytokine genes interleukin (IL)-1β, IL-6, and high mobility group box-1 (HMGB1) in FS and GEFS+. METHODS: Genotyping was performed in 208 subjects (57 patients with FS, 43 patients with GEFS+, and 108 controls) with the SNaPshot assay for IL-1β-31 (rs1143627), IL-1β-511 (rs16944), IL-6-572 (rs1800796), and HMGB1 3814 (rs2249825). Serum IL-1β, IL-6, and HMGB1 levels were analyzed within 2 hours after seizure attacks using the ELISA in only 68 patients (38 FS, 10 GEFS+, and 20 controls). The allele distribution, genotype distribution, and correlations with serum cytokine levels were analyzed. RESULTS: Near-complete linkage disequilibrium exists between IL-1β-31 and IL-1β-511 variants. CT genotypes of these variants were associated with significantly higher postictal serum IL-1β levels than were CC+TT genotypes in FS (both p<0.05). CT genotypes of IL-1β-31 and IL-1β-511 variants were more strongly associated with FS than were CC+TT genotypes (odds ratio=1.691 and 1.731, respectively). For GEFS+, serum IL-1β levels after AFS for CT genotypes of IL-1β-31 and IL-1β-511 were also higher than for CC+TT genotypes. No significant associations were found for IL-6 and HMGB1. CONCLUSIONS: Genetic variants located in IL-1β-31 and IL-1β-511 promotor regions are correlated with higher postictal IL-1β levels in FS. These results suggest that IL-1 gene cluster variants in IL-1β-31 and IL-1β-511 are a host genetic factor for provoking FS in Korean children.


Subject(s)
Alleles , Child , Enzyme-Linked Immunosorbent Assay , Epilepsy , Epilepsy, Generalized , Fever , Genetic Predisposition to Disease , Genotype , HMGB1 Protein , Humans , Inflammation , Interleukin-1 , Interleukin-6 , Interleukins , Linkage Disequilibrium , Multigene Family , Promoter Regions, Genetic , Seizures , Seizures, Febrile
14.
Article in English | WPRIM | ID: wpr-719295

ABSTRACT

BACKGROUND AND PURPOSE: This study investigated the seizure recurrence rate and potential predictors of seizure recurrence following antiepileptic drug (AED) withdrawal after resective epilepsy surgery in children with focal cortical dysplasia (FCD). METHODS: We retrospectively analyzed the records of 70 children and adolescents with FCD types I, II, and IIIa who underwent resective epilepsy surgery between 2004 and 2015 and were followed for at least 2 years after surgery. RESULTS: We attempted AED withdrawal in 40 patients. The median time of starting the AED reduction was 10.8 months after surgery. Of these 40 patients, 14 patients (35%) experienced seizure recurrence during AED reduction or after AED withdrawal. Half of the 14 patients who experienced recurrence regained seizure freedom after AED reintroduction and optimization. Compared with their preoperative status, the AED dose or number was decreased in 57.1% of patients, and remained unchanged in 14.3% after surgery. A multivariate analysis found that incomplete resection (p=0.004) and epileptic discharges on the postoperative EEG (p=0.025) were important predictors of seizure recurrence after AED withdrawal. Over the mean follow-up duration of 4.5 years after surgery, 34 patients (48.6% of the entire cohort) were seizure-free with and without AEDs. CONCLUSIONS: Children with incomplete resection and epileptic discharges on postoperative EEG are at a high risk of seizure recurrence after drug withdrawal. Complete resection of FCD may lead to a favorable surgical outcome and successful AED withdrawal after surgery.


Subject(s)
Adolescent , Anticonvulsants , Child , Electroencephalography , Epilepsy , Follow-Up Studies , Freedom , Humans , Malformations of Cortical Development , Multivariate Analysis , Recurrence , Retrospective Studies , Seizures
15.
Article in English | WPRIM | ID: wpr-788776

ABSTRACT

Focal cortical dysplasia (FCD) is the major cause of intractable focal epilepsy in childhood leading to epilepsy surgery. The overall seizure freedom after surgery ranges between 50–75% at 2 years after surgery and the long-term seizure freedom remain relatively stable. Seizure outcome after surgery depends on a various factors such as pathologic etiologies, extent of lesion, and types of surgery. Therefore, seizure outcome after surgery for FCD should be analyzed carefully considering cohorts' characteristics. Studies of pediatric epilepsy surgery emphasize the early surgical intervention for a better cognition. Early surgical intervention and cessation of seizure activity are important for children with intractable epilepsy. However, there are limited data on the cognitive outcome after surgery in pediatric FCD, requiring further investigation. This paper reviews the seizure and cognitive outcomes of epilepsy surgery for FCD in children. Several prognostic factors influencing seizure outcome after surgery will be discussed in detail.


Subject(s)
Child , Cognition , Drug Resistant Epilepsy , Epilepsies, Partial , Epilepsy , Freedom , Humans , Malformations of Cortical Development , Patient Outcome Assessment , Pediatrics , Seizures
16.
Article in English | WPRIM | ID: wpr-717425

ABSTRACT

BACKGROUND AND PURPOSE: Paroxysmal dyskinesia is a genetically and clinically heterogeneous movement disorder. Recent studies have shown that it exhibits both phenotype and genotype overlap with other paroxysmal disorders as well as clinical heterogeneity. We investigated the clinical and genetic characteristics of paroxysmal dyskinesia in children. METHODS: Fifty-five patients (16 from 14 families and 39 sporadic cases) were enrolled. We classified them into three phenotypes: paroxysmal kinesigenic dyskinesia (PKD), paroxysmal nonkinesigenic dyskinesia (PNKD), and paroxysmal exercise-induced dyskinesia (PED). We sequenced PRRT2, SLC2A1, and MR-1 in these patients and reviewed their medical records. RESULTS: Forty patients were categorized as PKD, 14 as PNKD, and 1 as PED. Thirty-eight (69.1%) patients were male, and their age at onset was 8.80±4.53 years (mean±SD). Dystonia was the most common symptom (38 patients, 69.1%). Pathogenic variants were identified in 20 patients (36.4%): 18 with PRRT2 and 2 with SLC2A1. All of the patients with PRRT2 mutations presented with PKD alone. The 2 patients carrying SLC2A1 mutations presented as PNKD and PED, and one of them was treated effectively with a ketogenic diet. Six mutations in PRRT2 (including 2 novel variants) were identified in 9 of the 13 tested families (69.2%) and in 8 patients of the 25 tested sporadic cases (32.0%). There were no significant differences in clinical features or drug response between the PRRT2-positive and PRRT2-negative PKD groups. CONCLUSIONS: This study has summarized the clinical and genetic heterogeneity of paroxysmal dyskinesia in children. We suggest that pediatric paroxysmal dyskinesia should not be diagnosed using clinical features alone, but by combining them with broader genetic testing.


Subject(s)
Age of Onset , Child , Chorea , Dyskinesias , Dystonia , Genetic Heterogeneity , Genetic Testing , Genotype , Humans , Diet, Ketogenic , Male , Medical Records , Movement Disorders , Phenotype , Population Characteristics
17.
Article in English | WPRIM | ID: wpr-717051

ABSTRACT

BACKGROUND: Chromosomal microarray (CMA) testing is a first-tier test for patients with developmental delay, autism, or congenital anomalies. It increases diagnostic yield for patients with developmental delay or intellectual disability. In some countries, including Korea, CMA testing is not yet implemented in clinical practice. We assessed the diagnostic utility of CMA testing in a large cohort of patients with developmental delay or intellectual disability in Korea. METHODS: We conducted a genome-wide microarray analysis of 649 consecutive patients with developmental delay or intellectual disability at the Seoul National University Children's Hospital. Medical records were reviewed retrospectively. Pathogenicity of detected copy number variations (CNVs) was evaluated by referencing previous reports or parental testing using FISH or quantitative PCR. RESULTS: We found 110 patients to have pathogenic CNVs, which included 100 deletions and 31 duplications of 270 kb to 30 Mb. The diagnostic yield was 16.9%, demonstrating the diagnostic utility of CMA testing in clinic. Parental testing was performed in 66 patients, 86.4% of which carried de novo CNVs. In eight patients, pathogenic CNVs were inherited from healthy parents with a balanced translocation, and genetic counseling was provided to these families. We verified five rarely reported deletions on 2p21p16.3, 3p21.31, 10p11.22, 14q24.2, and 21q22.13. CONCLUSIONS: This study demonstrated the clinical utility of CMA testing in the genetic diagnosis of patients with developmental delay or intellectual disability. CMA testing should be included as a clinical diagnostic test for all children with developmental delay or intellectual disability.


Subject(s)
Autistic Disorder , Child , Cohort Studies , Diagnosis , Diagnostic Tests, Routine , Genetic Counseling , Humans , Intellectual Disability , Korea , Medical Records , Microarray Analysis , Parents , Polymerase Chain Reaction , Retrospective Studies , Seoul , Virulence
18.
Article in English | WPRIM | ID: wpr-72141

ABSTRACT

BACKGROUND AND PURPOSE: There are few studies that have investigated predictive factors related to migraine prophylaxis of which produced inconsistent results. The aim of this study was to identify factors that can predict the treatment response to topiramate prophylaxis in pediatric patients with migraine. METHODS: One hundred and thirteen patients who were older than 7 years and received topiramate for at least 3 months were recruited from the Seoul National University Bundang Hospital outpatient clinic from 2005 to 2014. A positive response was defined as a reduction of more than 50% in the number of migraine episodes after topiramate treatment. Proposed predictive factors such as migraine characteristics including severity and frequency were assessed, as were other data on sex, disease duration, associated symptoms, family history, and impairment of daily activities. RESULTS: Seventy patients (61.9%) responded to prophylactic treatment with topiramate. Patients who experienced significant impairment in daily activities showed significant benefit from the treatment (p=0.004). Sex, the severity, frequency, and duration of migraine episodes, disease duration, treatment duration, age at onset, and associated symptoms were not significantly related to a response to topiramate treatment. CONCLUSIONS: Migraine characteristics and associated symptoms were not significantly related to a response to topiramate treatment. However, patients with significant impairment in daily activities showed significant benefit from the treatment, and so prophylactic topiramate treatment should be strongly encouraged in this patient group.


Subject(s)
Age of Onset , Humans , Migraine Disorders , Outpatient Clinics, Hospital , Seoul
19.
Article in English | WPRIM | ID: wpr-79076

ABSTRACT

Syringomyelia is a disorder in which a cavity has formed within the spinal cord. Idiopathic syringomyelia is not associated with identifiable causes such as Chari type 1 malformation, spinal cord tumor, vascular malformation, tethered cord, arachnoiditis, hydrocephalus, or previous spinal surgery. The main neurologic symptoms of idiopathic syringomyelia are toe-walking, constipation, incontinence, abnormal reflexes, and lower extremity weakness. Patients may present with various symptoms such as scoliosis, cutaneous markers, pain in the lower extremities or back, or may be asymptomatic. Herein, we report a young child with idiopathic syringomyelia presenting with subtle neck pain. A 23-month-old boy visited the neurologic clinic after 3 months of right occipital area neck pain. He had no history of trauma or central nervous system infection, and neurologic examination results were normal except for right posterior neck hyperesthesia. Brain and spinal magnetic resonance imaging showed an ovoid intramedullary cystic lesion (9.7×5.0×4.7 mm) at C6/7 of the spinal cord. There was no evidence of Chiari malformation or other lesions that can be primary pathologies of syringomyelia. Electromyogram/nerve conduction velocity results were normal. The subject was diagnosed as idiopathic syringomyelia. His symptoms and neurologic/radiologic indications showed no change at a 1-year follow-up. Idiopathic syringomyelia symptoms are varied and may be overlooked by physicians. Pediatricians may consider syringomyelia if patients complain about persistent sensory abnormality. All patients who present with syringomyelia should undergo detailed neuroimaging of the entire neuraxis to elucidate the proximate cause of the lesion.


Subject(s)
Arachnoid , Arachnoiditis , Brain , Central Nervous System Infections , Child , Constipation , Follow-Up Studies , Humans , Hydrocephalus , Hyperesthesia , Infant , Lower Extremity , Magnetic Resonance Imaging , Male , Neck , Neck Pain , Neuroimaging , Neurologic Examination , Neurologic Manifestations , Pathology , Reflex, Abnormal , Scoliosis , Spinal Cord , Spinal Cord Neoplasms , Syringomyelia , Vascular Malformations
20.
Article in English | WPRIM | ID: wpr-224343

ABSTRACT

BACKGROUND: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare inherited disorder characterized by infantile-onset macrocephaly, slow neurologic deterioration, and seizures. Mutations in the causative gene, MLC1, are found in approximately 75% of patients and are inherited in an autosomal recessive manner. We analyzed MLC1 mutations in five unrelated Korean patients with MLC. METHODS: Direct Sanger sequencing was used to identify MLC1 mutations. A founder effect of the p.Ala275Asp variant was demonstrated by haplotype analysis using single-nucleotide polymorphic (SNP) markers. Multiple ligation-dependent probe amplification (MLPA) and comparative genomic hybridization plus SNP array were used to detect exonic deletions or uniparental disomy (UPD). RESULTS: The most prevalent pathogenic variant was c.824C>A (p.Ala275Asp) found in 7/10 (70%) alleles. Two pathogenic frameshift variants were found: c.135delC (p.Cys46Alafs*12) and c.337_353delinsG (p.Ile113Glyfs*4). Haplotype analysis suggested that the Korean patients with MLC harbored a founder mutation in p.Ala275Asp. The p.(Ile113Glyfs*4) was identified in a homozygous state, and a family study revealed that only the mother was heterozygous for this variant. Further analysis of MLPA and SNP arrays for this patient demonstrated loss of heterozygosity of chromosome 22 without any deletion, indicating UPD. The maternal origin of both chromosomes 22 was demonstrated by haplotype analysis. CONCLUSIONS: This study is the first to describe the mutational spectrum of Korean patients with MLC, demonstrating a founder effect of the p.Ala275Asp variant. This study also broadens our understanding of the mutational spectrum of MLC1 by demonstrating a homozygous p.(Ile113Glyfs*4) variant resulting from UPD of chromosome 22.


Subject(s)
Alleles , Chromosomes, Human, Pair 22 , Comparative Genomic Hybridization , Exons , Founder Effect , Haplotypes , Humans , Leukoencephalopathies , Loss of Heterozygosity , Megalencephaly , Mothers , Seizures , Uniparental Disomy
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