Hereditary Leiomyomatosis and Renal Cell Cancer: A Case Report of Pilar Leiomyomatosis with History of Kidney Cancer and Review of the Literature

Pilar leiomyoma or piloleiomyoma is a benign neoplasm of the smooth muscle arising from the arrector pili muscle. It manifests as brown to red firm papulonodules with sites of predilection being the face, trunk, and extensor surfaces of the extremities. Histologically, the lesions exhibit ill-defined dermal tumors with interlacing fascicles of spindle cells. Some genodermatoses are characterized by the development of visceral tumors and cutaneous leiomyomatosis such as Reed’s syndrome, and hereditary leiomyomatosis and renal cell cancer (HLRCC). A 55-year-old male presented with reddish-brown papules and nodules on the face and upper back, accompanied by sharp episodic pain on the face. He had undergone nephrectomy for renal cancer 9 years ago, and his younger brother had similar cutaneous manifestation. Histopathologic findings were consistent with pilar leiomyoma, showing bundles of smooth muscle tumors in the dermis. Based on the clinical information including clinical features, past medical history, and family history, HLRCC was highly suspected.To confirm the diagnosis, whole exome sequencing was performed using peripheral blood, which revealed a novel point mutation (c.739G>A, p.Glu247Lys) in the fumarate hydratase (FH) gene. We describe a confirmed case of HLRCC, which is a genetic disorder with a potential to cause visceral cancers, which dermatologists might overlook as a benign condition.

Variant of CHD1 gene resulting in a Korean case of Pilarowski-Bjornsson syndrome

Many monogenic neurodevelopmental disorders have been newly identified in recent years owing to the rapid development of genetic sequencing technology. These include variants of the epigenetic machinery – up to 300 known epigenetic factors of which about 50 have been linked to specific clinical phenotypes. Chromodomain, helicase, DNA binding 1 (CHD1) is an ATP-dependent chromatin remodeler, known to be the causative gene of the autosomal dominant neurodevelopmental disorder Pilarowski-Bjornsson syndrome. Patients exhibit various degrees of global developmental delay, autism, speech apraxia, seizures, growth retardation, and craniofacial dysmorphism. We report the first case of Pilarowski-Bjornsson syndrome in Korea, due to a de novo missense variant of the CHD1 gene (c.862A>G, p.Thr288Ala) in a previously undiagnosed 17-yearold male. His infantile onset of severe global developmental delay, intellectual disability, speech apraxia, and failure to thrive are compatible with Pilarowski-Bjornsson syndrome. We also noted some features not previously reported in this syndrome such as skeletal dysplasia and ichthyosis. Further studies are needed to discover the specific phenotypes and pathogenic mechanisms behind this rare disorder.

Variations of Resting-State EEG-Based Functional Networks in Brain Maturation From Early Childhood to Adolescence

Background@#and Purpose Alterations in human brain functional networks with maturation have been explored extensively in numerous electroencephalography (EEG) and functional magnetic resonance imaging studies. It is known that the age-related changes in the functional networks occurring prior to adulthood deviate from ordinary trajectories of networkbased brain maturation across the adult lifespan. @*Methods@#This study investigated the longitudinal evolution of resting-state EEG-based functional networks from early childhood to adolescence among 212 pediatric patients (age 12.2± 3.5 years, range 4.4–17.9) in 6 frequency bands using 8 types of functional connectivity measures in the amplitude, frequency, and phase domains. @*Results@#Electrophysiological aspects of network-based pediatric brain maturation were characterized by increases in both functional segregation and integration up to middle adolescence. EEG oscillations in the upper alpha band reflected the age-related increases in mean node strengths and mean clustering coefficients and a decrease in the characteristic path lengths better than did those in the other frequency bands, especially for the phase-domain functional connectivity. The frequency-band-specific age-related changes in the global network metrics were influenced more by volume-conduction effects than by the domain specificity of the functional connectivity measures. @*Conclusions@#We believe that this is the first study to reveal EEG-based functional network properties during preadult brain maturation based on various functional connectivity measures. The findings potentially have clinical applications in the diagnosis and treatment of age-related brain disorders.

Wide heterogeneity of congenital myasthenic syndromes: analysis of clinical experience in a tertiary center

Purpose@#Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous group of disorders characterized by impaired neuromuscular transmission. This study aims to provide the clue for early diagnosis and improved therapeutic strategies in CMS. @*Materials and Methods@#Through the targeted panel sequencing including twenty CMS causative genes, eleven patients were genetically confirmed and enrolled in this study. A retrospective medical record review was carried out for the clinical and laboratory data analysis. @*Results@#The age of patients ranged from 5 to 23 years, with the median age of 16 years. The peak age at onset of symptoms was the neonatal period. Seven out of the eleven patients were symptomatic at birth. The most commonly reported initial finding was generalized hypotonia with poor sucking and crying. Mean time to accurate diagnosis was 9.3±5.0 years. Total fifteen different variants in seven genes associated with CMS (DOK7, AGRN, RAPSN, CHRNE, COLQ, SLC5A7, and GFPT1) were identified. @*Conclusion@#We describe the clinical and genetic characteristics of CMS patients and treatment outcome in a single tertiary center. High clinical suspicion and timely molecular diagnosis is particularly important for the tailored therapy to maximize clinical improvement in CMS.

Wide heterogeneity of congenital myasthenic syndromes: analysis of clinical experience in a tertiary center

Purpose@#Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous group of disorders characterized by impaired neuromuscular transmission. This study aims to provide the clue for early diagnosis and improved therapeutic strategies in CMS. @*Materials and Methods@#Through the targeted panel sequencing including twenty CMS causative genes, eleven patients were genetically confirmed and enrolled in this study. A retrospective medical record review was carried out for the clinical and laboratory data analysis. @*Results@#The age of patients ranged from 5 to 23 years, with the median age of 16 years. The peak age at onset of symptoms was the neonatal period. Seven out of the eleven patients were symptomatic at birth. The most commonly reported initial finding was generalized hypotonia with poor sucking and crying. Mean time to accurate diagnosis was 9.3±5.0 years. Total fifteen different variants in seven genes associated with CMS (DOK7, AGRN, RAPSN, CHRNE, COLQ, SLC5A7, and GFPT1) were identified. @*Conclusion@#We describe the clinical and genetic characteristics of CMS patients and treatment outcome in a single tertiary center. High clinical suspicion and timely molecular diagnosis is particularly important for the tailored therapy to maximize clinical improvement in CMS.

A familial case of limb-girdle muscular dystrophy with CAV3 mutation

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.

Current Clinical Features of Febrile Seizures in a Pediatric Emergency Room / 이화의대지

OBJECTIVES: To expand current knowledge on febrile seizures (FSs), the most common childhood seizure disorder, we investigated clinical features and risk factors of FS in the pediatric emergency department of a center in western Seoul. METHODS: Children with FS that visited the pediatric emergency room of the Ewha Womans University Medical Center from January to December 2014 were included in this study. A retrospective medical record review was conducted for a total of 404 seizure events relative to 265 patients. RESULTS: A total of 150 boys and 115 girls were enrolled. Children presenting their first FSs were 70.9% (n=188). Average age of FS onset was 28.9 months. Family history was reported in 95 children (36.8%) with higher relevance of paternal inheritance (44.2%, n=42/95). More than half of the seizures (56.4%, n=228/404) occurred on the first day of fever. The most common cause of fever was upper respiratory tract infection (65.8%, n=266/404). Children attending a daycare center had higher incidence of multiple FS compared to those cared for at home. Approximately one third of seizure events (31.7%, n=128/404) were admission cases, mainly because of prolonged fever. CONCLUSION: FS is a common neurologic disorder with relatively high admission rate among pediatric emergency department visits. Daycare attendance is associated with current increased incidence of multiple FS. Further study with long-term follow up is necessary to expand knowledge on improving clinical care strategy in FS.

A Case of Pediatric Nephrolithiasis Associated with Topiramate Treatment

Topiramate is an antiepileptic drug widely used to treat various seizures, mood disorders and migraine based on its various pharmacological mechanisms. Even though nephrolithiasis is listed as one of its side effects, there have been no cases reporting nephrolithiasis caused by use of topiramate on Korean pediatric patients. Since the use of topiramate is increasing in many patients, the possibility of nephrolithiasis after the treatment needs to be considered. Here, we report our experience in correcting neprholithiasis by simply discontinuing topiramate without administering any additional treatments.

Efficacy and Safety of Levetiracetam in Children Younger than 4 Years with Intractable Epilepsy / 대한간질학회지

PURPOSE: The aim of this study was to evaluate the efficacy and safety of levetiracetam in children younger than 4 years with intractable epilepsy. METHODS: A retrospective analysis of pediatric epilepsy patients was performed. Data were obtained from the medical records of 30 patients (male 19, female 11) with intractable epilepsy, who were treated with levetiracetam. RESULTS: Seizure types were partial in 18, and generalized in 12. Fifteen patients had symptomatic etiologies. The median age of the patients at the time of levetiracetam administration was 26 months old (range: 4-47 months). The median starting dose was 13 mg/kg/ day, and the median maintenance dose was 52 mg/kg/day (range: 10-123 mg/kg/day). Ten (10/30, 33%) patients experienced more than 50% reduction in seizure frequency, and 4 (4/30, 13%) partial epilepsy patients became seizure-free. Eight partial epilepsy patients (44%) had more than 50% seizure reduction, while 2 patients (17%) with generalized epilepsy did. All of patients with infantile spasms and Lennox-Gastaut syndrome except one, had less than 50% reduction in seizure frequency. Adverse events reported in 8 patients (27%), included lethargy, behavioral problems, sleep disturbance, and seizure aggravation. CONCLUSIONS:Levetiracetam is effective in children aged 4 years or less with intractable epilepsy, and also seems to be safe to use in this age group.

A case of Menkes disease with unusual hepatomegaly / 소아과

Menkes disease is an X-linked recessive copper transport disorder characterized by neurological deterioration, connective-tissue damage, and abnormal hair growth. It is caused by the mutation of the ATP7A gene. This report describes a four-month-old boy with neurological symptoms typical of Menkes disease plus unusual liver involvement. He developed seizures at three months of age and exhibited hypotonia, cephalhematoma, a sagging face, redundant and hypopigmented skin, and abnormal hair growth. In addition, he had unexplained hepatomegaly and high hepatic transaminase. We confirmed the diagnosis of Menkes disease by mutation analysis of the ATP7A gene. To exclude other possible causes for the hepatic abnormalities, a liver biopsy was performed, revealing intracytoplasmic cholestasis, focal spotty necrosis, and minimal lobular activity. The patient's liver involvement may be an underestimated complication of Menkes disease.

Clinical Characteristics of Childhood Pompe Disease

PURPOSE: Pompe disease is one of the glycogen storage diseases caused by a deficiency of acid alpha-glycosidase. This enzyme defect results in lysosomal glycogen accumulation in many tissues and shows a various spectrum of clinical features from early infantile hypotonia to mild weakness. For the investigation of the clinical characteristics of Pompe disease, we reviewed 6 cases of childhood Pompe disease diagnosed by muscle biopsy and acid alpha-glycosidase assay. METHODS: We reviewed the medical records of 6 childhood Pompe disease patients in Seoul National University Children's Hospital, retrospectively from January 2001 to October 2006. RESULTS: The age of the symptom onset was 1 month to 11 years(mean 2.2 years) and the diagnosis was made at the age of 8 months to 14 years(mean 5.3 years). The patients showed delayed motor development, motor weakness, hypotonia, cardiomegaly, hypertrophic cardiomyopathy, hepatomegaly, recurrent pulmonary infections but the severity was very diverse. Liver transaminase and CK levels were elevated in all of the patients. Their muscle biopsy showed the characteristic accumulation of purple colored glycogen granules and the degeneration of myofibers. CONCLUSION: Childhood Pompe disease had various clinical features and severities depending on the age of onset, organ involvement and the rate of progression. Enzyme replacement therapy may modify the disease courses, so we need to diagnose earlier for the treatment at an optimal time.