• Journal of Genetic Medicine
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• v.13 no.2
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• pp.105-110
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• 2016

Congenital myotonic dystrophy (CMD) which is transmitted in an autosomal-dominant manner, can also be observed in newborns born to asymptomatic parents who have a myotonic dystrophy type 1 or premutation allele, especially from the mother. A mother with myotonic dystrophy could be subfertile and the pregnancy could be complicated with the risk of a preterm birth. Newborns with CMD may demonstrate symptoms such as hypotonia and poor motor activity, as well as respiratory and feeding difficulties. Additionally, CMD has a high mortality rate at birth. Detection of the signs and symptoms during pregnancy is helpful for a prenatal diagnosis of CMD in cases where the family history is not known.

• Journal of Genetic Medicine
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• v.6 no.2
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• pp.166-169
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• 2009

Not only is the concurrence of congenital myotonic dystrophy (CDM) and subgaleal hematoma (SGH) hardly ever seen but also the development of SGH during unassisted vaginal delivery is rare. We report a boy who developed huge SGH in vaginal delivery without any use of vacuum or forceps and later was diagnosed as maternally transmitted CDM. The boy had prenatal history of polyhydramnios and decreased fetal movement. Six hours after birth, severe molding of the skull associated with huge SGH on left parieto-occipital area was recognized by CT scan. At corrected age of two months, he was diagnosed as maternally transmitted CDM. This is the first report of CDM complicated by SGH occurring in non-instrumental vaginal delivery.

• Clinical and Experimental Pediatrics
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• v.62 no.2
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• pp.55-61
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• 2019

Purpose: Myotonic dystrophy, also known as dystrophia myotonica (DM), is an autosomal dominant disorder with 2 genetically distinct forms. DM type 1 (DM1) is the more common form and is caused by abnormal expansion of cytosine/thymine/guanine (CTG) repeats in the DM protein kinase (DMPK ) gene. Our study aimed to determine whether the age of onset is correlated with CTG repeat length in a population of pediatric patients with DM1. Methods: We retrospectively identified 30 pediatric patients with DM1 that underwent DMPK testing, of which the clinical data of 17 was sufficient. The cohort was divided into 2 subgroups based on the clinical phenotype (congenital-onset vs. late-onset) and number of CTG repeats (<1,000 vs. ${\geq}1,000$). Results: We found no significant difference between the age of onset and CTG repeat length in our pediatric patient population. Based on clinical subgrouping, we found that the congenital-onset subgroup was statistically different with respect to several variables, including prematurity, rate of admission to neonatal intensive care unit, need for respiratory support at birth, hypotonia, dysphagia, ventilator dependence, and functional status on last visit, compared to the late-onset subgroup. Based on genetic subgrouping, we found a single variable (poor feeding in neonate) that was significantly different in the large CTG subgroup than that in the small CTG subgroup. Conclusion: Clinical variables exhibiting statistically significant differences between the subgroups should be focused on prognosis and designing tailored management approaches for the patients; our findings will contribute to achieve this important goal for treating patients with DM1.

• Clinical and Experimental Pediatrics
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• v.50 no.9
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• pp.868-874
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• 2007

Purpose : We performed this study to investigate the perinatal and developmental features of the patients with congenital myotonic dystrophy (CDM) confirmed by the molecular genetic method and the clinical characteristics of their mother, and to identify the relation between the number of CTG repeats and the clinical severity.Methods : A retrospective review of the medical records and the results of the dystrophia myotonica protein kinase (DMPK) gene test was done for the patients who were confirmed as CDM through gene analysis from January 2001 to September 2006. Results : All of the eight patients (male 2, female 6) showed moderate to severe degree of perinatal distress and feeding difficulty associated with profound hypotonia. Three patients had the history of polyhydramnios and two patients had equinovarus deformity. The developmental milestones were delayed in all patients, which improved gradually with age. All of their mothers demonstrated myotonic symptoms and typical myopathic face. The number of CTG repeats in DMPK gene analysis ranged 1,000-2,083, and there was no significant correlation between the number of CTG repeats and the time of walking alone. Conclusion : All patients with CDM presented with severe hypotonia in perinatal period, and developmental delay thereafter, which were improved with age. All of their mothers manifested myotonic symptoms with typical myopathic face, and the identification of such features greatly contributed to the diagnosis of the patients. The number of CTG repeats had no significant influence on the motor development.

• Journal of the Korean Child Neurology Society
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• v.26 no.4
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• pp.189-196
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• 2018

Purpose: Floppy infants or congenital hypotonia indicates decreased muscle tone in infants secondary to abnormalities of the central or the peripheral nervous system, or both. Previous literature classified its causes as those attributable to a central vs. peripheral origin; however, recent studies have introduced a newer classification describing a combined origin. We invenstigated floppy infants by applying the new etiological classification and reviewed the most common etiologies based on the age of presentation. We additionally reviewed the clinical characteristics, diagnoses, and the developmental outcomes in these infants. Methods: We retrospectively reviewed the electronic medical charts and recruited 116 infants diagnosed with floppy infant syndrome between January 2005 and December 2016 at Severance Children's Hospital. Among these infants, 66 with a confirmed diagnosis were reviewed for the etiological classification. Information regarding developmental outcomes was obtained via phone interviews with the infants' families. Results: Based on the new etiological classification, among 69 infants with a confirmed diagnosis, in 40 (34.5%) this syndrome was of central origin, in 19 (16.4%) of peripheral origin, and in 10 (8.6%) of combined origin. Prader-Willi syndrome, myotonic dystrophy, and spinal muscular atrophy were the most common disorders observed and combined hypotonia showed the poorest developmental outcome. Conclusion: The study states the importance of proper evaluation of etiological diagnosis and optimal intervention for developmental prognosis. The introduction of a new etiological group of combined hypotonia especially emphasizes regular monitoring and timely rehabilitative intervention in patients for the better quality of life in them as well as their caregivers.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.1
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• pp.1-8
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• 2005

Myotonic Dystrophies type 1 and 2 (DM1/2) are neuromuscular disorders which belong to a group of genetic diseases caused by unstable CTG triplet repeat (DM1) and CCTG tetranucleotide repeat (DM2) expansions. In DM1, CTG repeats are located within the 3' untranslated region of myotonin protein kinase (DMPK) gene on chromosome 19q. DM2 is caused by expansion of CCTG repeats located in the first intron of a gene coding for zinc finger factor 9 on chromosome 3q. The CTG and CCTG expansions are located in untranslated regions and are expressed as pre-mRNAs in nuclei (DM1 and DM2) and as mRNA in cytoplasm (DM1). Investigations of molecular alterations in DM1 discovered a new molecular mechanism responsible for this disease. Expansion of un-translated CUG repeats in the mutant DMPK mRNA disrupts biological functions of two CUG-binding proteins, CUGBP and MNBL. These proteins regulate translation and splicing of mRNAs coding for proteins which play a key role in skeletal muscle function. Expansion of CUG repeats alters these two stages of RNA metabolism in DM1 by titrating CUGBP1 and MNBL into mutant DMPK mRNA-protein complexes. Mouse models, in which levels of CUGBP1 and MNBL were modulated to mimic DM1, showed several symptoms of DM1 disease including muscular dystrophy, cataracts and myotonia. Mis-regulated levels of CUGBP1 in newborn mice cause a delay of muscle development mimicking muscle symptoms of congenital form of DM1 disease. Since expansion of CCTG repeats in DM2 is also located in untranslated region, it is predicted that DM2 mechanisms might be similar to those observed in DM1. However, differences in clinical phenotypes of DM1 and DM2 suggest some specific features in molecular pathways in both diseases. Recent publications suggest that number of pathways affected by RNA CUG and CCUG repeats could be larger than initially thought. Detailed studies of these pathways will help in developing therapy for patients affected with DM1 and DM2.

• Journal of Genetic Medicine
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• v.10 no.1
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• pp.33-37
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• 2013

Purpose: Myotonic dystrophy 1 (DM1, OMIM 160900) is an autosomal-dominant muscular disorder caused by an expansion of CTG repeats in the 3' UTR of the DMPK gene. Variable expansions of CTG repeats preclude the accurate determination of repeat size. We tried to show the clinical and analytical validity of the application of Southern blotting after long-range PCR was demonstrated in Korean DM1 patients. Materials and Methods: The Southern blotting of long-range PCR was applied to 1,231 cases with clinical suspicion of DM1, between 2000 and 2011. PCR was performed using genomic DNA with forward 5'-CAGTTCACAACCGCTCCGAGC-3' and reverse 5'-CGTGGAGGATGGAACACGGAC-3' primers. Subsequently, the PCR fragments were subjected to gel electrophoresis, capillary transfer to a nylon membrane, hybridization with a labeled (CAG)10 probe. The correlation between clinical manifestations and the CTG repeat expansions were analyzed. Results: Among a total of 1,231 tested cases, 642 individuals were diagnosed with DM1 and the range of the detected expansion was 50 to 2,500 repeats; fourteen cases with mild DM1 ($75{\pm}14$ repeats), 602 cases with classical DM1 ($314{\pm}143$ repeats), and 26 cases with congenital DM1 ($1,219{\pm}402$ repeats). The positive and negative predictive values were 100%. The age at test requested and the CTG repeat numbers were inversely correlated (R=-0.444, P<0.01). Conclusion: This study indicates that Southern blotting after long-range PCR is a reliable diagnostic method DM1.

• Annals of Clinical Neurophysiology
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• v.14 no.2
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• pp.80-82
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• 2012

• Clinical and Experimental Pediatrics
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• v.49 no.11
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• pp.1158-1166
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• 2006

Purpose : The purpose of this study is to make a diagnostic classification and discuss a diagnostic strategy of floppy infants by investigating clinical, neurological, electrophysiological, and genetic analysis of infants admitted to intensive care units with the complaint of hypotonia. Methods : A retrospective study was performed from Jan. 1993 to Dec. 2005 in neonatal and pediatric intensive care units of Seoul National University Children's Hospital. Clinical features and all tests related to hypotonia were investigated. Results : There were 21 cases of floppy infants admitted to intensive care units. Final diagnosis was classified as centra (7 cases[33.3 percent]), peripheral (11 cases [52.4 percent]), and unspecified (3 cases [14.3 percent]). Among the central group, three patients were diagnosed as hypoxic ischemic encephalopathy, two patients as Prader-Willi syndrome, one patient as chromosomal disorder, and one patient as transient hypotonia. Among the peripheral group, four patients were diagnosed as myotubular myopathy, three patients as SMA type 1, two patients as congenital myotonic dystrophy, one patient as congenital muscular dystrophy, and one as unspecified motor-neuron disease. Motor power was above grade 3 on average, and deep tendon reflex was brisk in the central group. Among investigations, electromyography showed 66 percent sensitivity in the peripheral group, and muscle biopsy was all diagnostic in the peripheral group. Brain image was diagnostic in the central group, and Prader-Willi FISH or karyotyping was helpful in diagnosis in central group. Morbidity and mortality was more severe in the peripheral group Conclusion : Classification of diagnosis by clinical characteristics in this study, and application of investigations step by step, may provide an effective diagnostic strategy.