• Clinical and Experimental Pediatrics
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• v.57 no.2
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• pp.75-78
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• 2014

Purpose: This study aimed to investigate the clinical features of macrocephaly at birth in Korea using ultrasonography. Methods: We retrospectively investigated the medical records of full-term birth neonates in Cheil General Hospital & Women's Healthcare Center from January 2000 to June 2012. The following parameters were recorded and analyzed: gestational age, sex, birth weight, height, occipitofrontal circumference (OFC), physical examination, perinatal problems, and ultrasonography results. Macrocephaly was diagnosed when the OFC was greater than two standard deviations, based on the 2007 Korean National Growth Charts. Results: There were 75 neonates with macrocephaly at birth (52 boys and 23 girls), with a mean OFC of $38.1{\pm}0.49cm$. A comparison of the birth weight and height with the OFC value showed that height was correlated with OFC (r=0.35) but birth weight was not correlated with OFC (r=0.06). There were no remarkable findings in 56 cases (75%). Germinal matrix hemorrhage was identified in 10 cases (13%). An enlarged cerebrospinal fluid space was found in 5 cases (6.7%). There were 3 cases of mega-cisterna magna (4%), 1 case of ventriculomegaly, and 1 case of an enlarged interhemispheric space (6 mm) among these patients. In addition, a choroid plexus cyst was seen in 1 case. Mineralizing vasculopathy in both basal ganglia with no evidence of congenital infection was found in 2 cases and an asymptomatic subarachnoid hemorrhage was found in 1 case. Conclusion: Our results indicate that macrocephaly at birth has benign ultrasonography findings and shows a pattern of male dominance.

• Journal of Korean Neurosurgical Society
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• v.30 no.sup1
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• pp.159-164
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• 2001

Reduction cranioplasty is one of the treatment modality among many treatment options for macrocephaly with hydrocephalus. The most previous techniques of reduction cranioplasty have some disadvantages such as difficult airway maintenance, pressure sore due to modified prone position, severe venous infarct due to obstruction of venous blood flow and large amount of bleeding from the dissection of superior sagittal sinus to obtain bone fragment needed. A 28-month-old girl had extreme macrocephaly. She couldn't control head rotation and keep sitting position. The operation was performed at supine position with adequate exposure of entire calvarium and the hinge was made in occipital bone fragment that covered posterior part of superior sagittal sinus. Bleeding volume and the other complications were decreased and acceptable reduction was achieved with this method.

• Clinical and Experimental Pediatrics
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• v.59 no.sup1
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• pp.152-156
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• 2016

Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP), previously known as macrocephaly-cutis marmorata telangiectatica congenita and macrocephaly-capillary malformation syndrome, is a rare multiple-malformation syndrome that is characterized by progressive megalencephaly, capillary malformations of the midline face and body, or distal limb anomalies such as syndactyly. Herein, we report a female infant case that satisfies the recently proposed criteria of MCAP and describe the distinctive neuroradiological and morphological features. We have also reviewed recently published reports and the diagnostic criteria proposed by various authors in order to facilitate the clinical diagnosis of these children in pediatric neurology clinics.

• Clinical and Experimental Pediatrics
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• v.46 no.3
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• pp.295-301
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• 2003

Glutaric aciduria type 1(GA1) is an autosomal recessive disorder of the lysine, hydroxylysine and tryptophan metabolism caused by the deficiency of mitochondrial glutaryl-CoA dehydrogenase. This disease is characterized by macrocephaly at birth or shortly after birth and various neurologic symptoms. Between the first weeks and the 4-5th year of life, intercurrent illness such as viral infections, gastroenteritis, or even routine immunizations can trigger acute encephalopathy, causing injury to caudate nucleus and putamen. But intellectual functions are well preserved until late in the disease course. We report a one-month-old male infant with macrocephaly and hypotonia. In brain MRI, there was frontotemporal atrophy(widening of sylvian cistern). In metabolic investigation, there were high glutarylcarnitine level in tandem mass spectrometry and high glutarate in urine organic acid analysis, GA1 was confirmed by absent glutaryl-CoA dehydrogenase activity in fibroblast culture. He was managed with lysine free milk and carnitine and riboflavin. He developed well without a metabolic crisis. If there is macrocephaly in an infant with neuroradiologic sign of frontotemporal atrophy, GA1 should have a high priority in the differential diagnosis. Because current therapy can prevent brain degeneration in more than 90% of affected infants who are treated prospectively, recognition of this disorder before the brain has been injured is essential for treatment.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.20 no.1
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• pp.65-70
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• 2017

Bannayan-Riley-Ruvalcaba syndrome (BRRS) is one of the phosphatase and tensin homolog hamartoma tumor syndrome with a PTEN gene mutation. It is a rare dominant autosomal disorder characterized by cutaneous lipomas, macrocephaly, intestinal polyps, and developmental delay. Diagnosing this syndrome is important, because it may represent the pediatric phenotype of Cowden syndrome, in which there is an increased risk for malignant tumors in children. Until now, the prevalence of BRRS is unknown. Several dozen cases have been reported in the medical literature, but no case has been reported in Korea. Here we report a case of a 19-year-old girl who was diagnosed with BRRS because of macrocephaly, intellectual disability, and intestinal polyps. Her mother had similar findings and a PTEN mutation. Neither patient had mutations detected by conventional mutation-detection techniques, but a PTEN gene deletion was demonstrated by chromosomal microarray analysis.

• Journal of Genetic Medicine
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• v.16 no.1
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• pp.27-30
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• 2019

Smith-Kingsmore syndrome (SKS; OMIM 616638), also known as macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome (MINDS; ORPHA 457485), is a rare autosomal dominant disorder, the prevalence of which is not known. It is caused by a heterozygous germline mutation in MTOR (OMIM 601231). Ten different MTOR germline mutations in 27 individuals have been reported in the medical literature to date. These were all gain-of-function missense variants, and about half of the 27 individuals had c.5395G>A p.(Glu1799Lys) in MTOR. Here, I report for the first time a Korean patient with the heterozygous germline mutation c.5395G>A p.(Glu1799Lys) in MTOR. It was found to be a de novo mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing. The patient showed typical clinical features of SKS, including macrocephaly/megalencephaly; moderate intellectual disability; seizures; behavioral problems; and facial dysmorphic features of curly hair, frontal bossing, midface hypoplasia, and hypertelorism.

• Genes and Genomics
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• v.40 no.11
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• pp.1149-1155
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• 2018

Epileptic encephalopathies are genetically heterogeneous disorders which leads to epilepsy and cause neurological disorders. Seizure threshold 2 (SZT2) gene located on chromosome 1p34.2 encodes protein mainly expressed predominantly in the parietal and frontal cortex and dorsal root ganglia in the brain. Previous studies in mice showed that mutation in this gene can confers low seizure threshold, enhance epileptogenesis and in human may leads to facial dysmorphism, intellectual disability, seizure and macrocephaly. Objective of this study was to find out novel gene or novel mutation related to the gene phenotype. We have identified a large consanguineous Saudi family segregating developmental delay, intellectual disability, epilepsy, high forehead and macrocephaly. Exome sequencing was performed in affected siblings of the family to study the novel mutation. Whole exome sequencing data analysis, confirmed by subsequent Sanger sequencing validation study. Our results showed a novel homozygous mutation (c.9368G>A) in a substitution of a conserved glycine residue into a glutamic acid in the exon 67 of SZT2 gene. The mutation was ruled out in 100 unrelated healthy controls. The missense variant has not yet been reported as pathogenic in literature or variant databases. In conclusion, the here detected homozygous SZT2 variant might be the causative mutation that further explain epilepsy and developmental delay in this Saudi family.

• Clinical and Experimental Pediatrics
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• v.45 no.10
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• pp.1278-1282
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• 2002

Glutaric aciduria(type 1) is characterized clinically by progressive dystonia and dyskinesia in childhood, pathologically by degeneration of caudate and putamen, biochemically by tissue deficiency of glutaryl-CoA dehydrogenase(GCDH), and is transmitted as an autosomal recessive traits. Mutations of the GCDH gene on chromosome 19 have been implicated in the causation of glutaric aciduria(type 1). Macrocephaly in infancy and crossing of percentiles for head circumference are real clues to early diagnosis. Acute neuroregression of dystonia following an initial phase of normal or almost normal development is a common mode of presentation, at times preceded by seizures. We experienced a case of glutaric aciduria(type 1) in a 13-month old girl. She was admitted due to development delay and choreoasthetoid movememt that developed after generalized tonic-clonic type seizures. She was diagnosed as having glutaric aciduria(type 1) based on brain MRI and urine organic acid analysis finding.

• Journal of Korean Neurosurgical Society
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• v.44 no.4
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• pp.240-244
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• 2008

Objective : Sotos Syndrome is characterized by macrocephaly, overgrowth, and developmental delay, and more than 300 patients have been reported worldwide to date. The authors reviewed the clinical characteristics of 8 patients with Sotos Syndrome in Korea for a new understanding and treatment strategies. Methods : The medical records of a total of eight Korean children with Sotos Syndrome were reviewed. All patients underwent developmental checkup, lumbar punctures for measurement of intracranial pressure (ICP), brain and spine magnetic resonance imaging and computerized tomography. Results : All 8 patients showed macrocephaly and the characteristic craniofacial features of Sotos Syndrome. Other clinical characteristics shown were overgrowth (7/8), developmental delay (7/8), congenital heart defect (3/8), flat foot (8/8), scoliosis (4/8), spina bifida (8/8), hydrocephalus (4/8), cavum vergae (3/8), and increased subdural fluid collection (5/8). Mean ICP measured via lumbar puncture was $27.35{\pm}6.25\;cm$ $H_2O$ (range 20 to 36 cm $H_2O$). Two patients received ventriculo-peritoneal shunt, and 1 patient underwent subduro-peritoneal shunt with improvement. Spinal orthosis was applied to 4/5 patients with scoliosis and 4/8 children with flat foot were provided with foot orthosis. Conclusion : In this first Korean study of 8 Sotos Syndrome patients we demonstrated the presence of spina bifida and increased ICP, which had not been previously described. The authors therefore suggest that all patients with Sotos Syndrome should undergo examination for the presence of spina bifida, and that shunt procedures would improve development and alleviate clinical symptoms.

• Journal of Genetic Medicine
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• v.13 no.2
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• pp.99-104
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• 2016

$Cant{\acute{u}}$ syndrome (CS, OMIM 239850) is a very rare autosomal dominantly inherited genetic disease characterized by congenital hypertrichosis, neonatal macrosomia, a distinct facial features such as macrocephaly, and cardiac defects. Since the first description by $Cant{\acute{u}}$ et al. in 1982, about 50 cases have been reported to date. Recently, two causative genes for CS has been found by using exome sequencing analyses: ABCC9 and KCNJ8. Most cases of clinically diagnosed CS have resulted from de novo mutations in ABCC9. In this study, we report three independent Korean children with CS resulting from de novo ABCC9 mutations. Our patients had common clinical findings such as congenital hypertrichosis, distinctive facial features. One of them showed severe pulmonary hypertension and hypertrophic cardiomyopathy, which require medical treatment. And, two patients had a history of patent ductus arteriosus. Although two of our patients had shown early motor developmental delay, it was gradually improved during follow-up periods. Although CS is quite rare, there are the concerns about development of various cardiac problems in the lifetime. Therefore, an accurate diagnosis followed by appropriate management and genetic counseling should be provided to CS patients.