OBJECTIVETo investigate the clinical manifestations and to make genetic analysis in a pedigree with myotonic dystrophy disease.

METHODSThe proband and available family members were identified by neurological examination. The clinical manifestation of 8 patients (including the proband) was analyzed; the electromyographic data of 5 patients were compared with 6 other family members. Blood samples were obtained from the 7 patients of the family (excepting II6). DM(1) and DM(2) gene were amplified by PCR, tested by agarose electrophoresis, then analyzed by genetic analyzer.

RESULTSMyotonia and muscle weakness were the main manifestations associated with heart block (7/8) and cataract(6/7). Electromyologram showed myopathic abnormalities not only in patients but also in other members of the family (5/6). The CTG repeats in DM1 and CCTG repeats in DM2 were all in normal range.

CONCLUSIONThere likely to be new mutants in this DM pedigree and further study is needed.

Adult ; Base Sequence ; Female ; Humans ; Male ; Microsatellite Repeats ; genetics ; Molecular Sequence Data ; Myotonic Dystrophy ; genetics ; Myotonin-Protein Kinase ; Pedigree ; Polymerase Chain Reaction ; methods ; Protein-Serine-Threonine Kinases ; genetics

OBJECTIVE: To analyze the clinical, familial and hereditary features of myotonic dystrophy to improve the knowledge and provide molecule evidence for gene diagnosis and prenatal diagnosis of myotonic dystrophy or dystrophia myotonia (DM) families. METHODS: Clinical data of 2 DM families were collected based on the probands. The number of trinucleotide CTG repeat in the 3' untranslated region of myotonic dystrophy protein kinase (DMPK) gene on chromosome 19 was determined by DNA sequence and repeat fragment. RESULTS: Except for 1 subclinical patient, another 5 patients progressed slowly with the features of myotonic muscular weakness and atrophy. One patient had hatchet face, 1 had cataract and diabetes mellitus, and the other 3 were bald. Electromyologram showed 3 patients had myotonic discharge and myopathic abnormalities. The number of trinucleotide CTG repeat in the 3' untranslated region of DMPK gene of 5 patients exceeded 50. CONCLUSION DM can be anticipated. Gene analysis can verify the disease and identify subclinical patients. It helps to prevent the DM births by hereditary consultation performing prenatal diagnosis.
Adolescent ; Adult ; Female ; Humans ; Male ; Myotonic Dystrophy ; diagnosis ; genetics ; Myotonin-Protein Kinase ; Pedigree ; Polymerase Chain Reaction ; methods ; Protein-Serine-Threonine Kinases ; genetics ; Trinucleotide Repeats

OBJECTIVETo investigate a patient featuring a complex neuromuscular disease phenotype.

METHODSA comprehensive analysis integrating clinical investigation, electrophysiological testing, pathological analysis and mutation screening was carried out.

RESULTSThe patient has presented clinical and pathological manifestations mimicking Duchenne muscular dystrophy. However, genetic analysis has identified no deletion in 21 exons of Dystrophin gene, no pathologic expansion of CTG repeats in DMPK gene or CCTG repeats in ZFN9 gene. Instead, a homozygous deletion of exons 7 and 8 in SMN gene was discovered.

CONCLUSIONA rare case of spinal muscular atrophy (SMA) was verified by genetic diagnosis. SMA is a group of neuromuscular disorders with great phenotypic heterogeneity and sometimes cannot be diagnosed by clinical manifestations, electrophysiological and pathological changes alone. Genetic diagnosis has become indispensable for accurate diagnosis for patients suspected to have the disease.

Adult ; Diagnosis, Differential ; Humans ; Male ; Muscular Atrophy, Spinal ; diagnosis ; genetics ; pathology ; Myotonic Dystrophy ; diagnosis ; genetics ; pathology ; Myotonin-Protein Kinase ; Phenotype ; Protein-Serine-Threonine Kinases ; genetics ; SMN Complex Proteins ; genetics ; Young Adult

OBJECTIVETwo genetic loci are associated with the myotonic dystrophy (DM) phenotype: DM1 DMPK on chromosome 19, and DM2 ZNF9 on chromosome 3. The aim of this study was to investigate the molecular genetics of a pedigree with DM.

METHODSIn twenty-six individuals from a family with DM, the CTG repeats in DMPK and CCTG repeats in ZNF9were evaluated genetically, using Long Expand trade mark Template polymerase chain reaction (PCR), Southern blotting and genomic scanning.

RESULTSThe numbers of CTG and CCTG repeat were all in normal range. There was no significant difference between the CTG repeat size in DMPK gene and that 4 years later from the same individual. The Lod score values with short tandem repeats STR markers chosen in 19q and 3q were all smaller than 1, which suggested that no STR marker was linked with this DM family.

CONCLUSIONThere might be some other mutant in this DM pedigree. Further study should be done to find the genetic basis of this pedigree.

Adolescent ; Adult ; Blotting, Southern ; Child ; Female ; Humans ; Male ; Microsatellite Repeats ; genetics ; Middle Aged ; Myotonic Dystrophy ; genetics ; Myotonin-Protein Kinase ; Pedigree ; Polymerase Chain Reaction ; Protein-Serine-Threonine Kinases ; genetics ; RNA-Binding Proteins ; genetics ; Trinucleotide Repeats ; genetics

OBJECTIVE: Although the conventional prevalence of myotonic dystrophy is 1:8,000, the prevalence in Korean population was recently reported as 1:1,245. With higher domestic result than expected, we aimed to investigate the clinical characteristics of pregnancies complicated by congenital myotonic dystrophy in our institution. METHODS: We have reviewed 11 paired cases of neonates diagnosed with congenital myotonic dystrophy and their mothers between July 2004 and May 2014, with clinical features including maternal history of infertility, prenatal ultrasonographic findings, and neonatal outcomes. Cytosine-thymine-guanine (CTG) repeat expansion in the myotonic dystrophy protein kinase gene of both neonates and their mothers was also examined. RESULTS: None of mother was aware of their myotonic dystrophy traits before pregnancy. History of infertility followed by assisted reproductive technology accounted for 57.1% (4/7). Distinctive prenatal ultrasonographic finding was severe idiopathic polyhydramnios (66.7%, 4/6) with median amniotic fluid index of 43 (range, 37 to 66). In 37.5% (3/8) cases, decreased fetal movement was evident during prenatal ultrasound examination. For neonatal outcomes, more than half (6/11) were complicated with preterm birth and the proportion of 1-minute Apgar score <4 and 5-minute Apgar score <7 was 44.4% (4/9) and 66.7% (6/9), respectively. Most of neonates were admitted to the neonatal intensive care unit (9/10) because of hypotonia with respiratory problems and there was one infant death. Median number of cytosine-thymine-guanine repeats in mothers and neonates was 400 (range, 166 to 1,000) and 1,300 (range, 700 to 2,000), respectively. CONCLUSION: Our data suggest that severe idiopathic polyhydramnios with decreased fetal movement in pregnant women, especially with a history of infertility, requires differential diagnosis of congenital myotonic dystrophy.
Amniotic Fluid ; Apgar Score ; Diagnosis, Differential ; Female ; Fetal Movement ; Humans ; Infant Death ; Infant, Newborn ; Infertility ; Intensive Care, Neonatal ; Mothers ; Muscle Hypotonia ; Myotonic Dystrophy* ; Myotonin-Protein Kinase ; Polyhydramnios ; Pregnancy* ; Pregnant Women ; Premature Birth ; Prenatal Diagnosis ; Prevalence ; Reproductive Techniques, Assisted ; Ultrasonography

Congenital myotonic dystrophy (CMD) is an inherited neuromuscular disorder with cardiac rhythm abnormalities that may occur as a child grows. No report has described complete atrioventricular (AV) block detected in a neonate with CMD. We report a floppy infant of 31(+4) weeks gestation with complete AV block at birth, who was diagnosed with CMD by Southern analysis. She recovered from complete AV block 32 hr after temporary transcutaneous pacing was applied. To the best our knowledge, this is the first recorded case of a complete AV block accompanied by CMD during the neonatal period. When a newborn has a complete AV block, the physician should consider the possibility of the CMD and conduct a careful physical examination.
3' Untranslated Regions ; Atrioventricular Block/complications/*diagnosis ; Blood Gas Monitoring, Transcutaneous ; Chromosomes, Human, Pair 9 ; Electrocardiography ; Female ; Humans ; Infant, Newborn ; Myotonic Dystrophy/complications/*diagnosis/genetics ; Myotonin-Protein Kinase/genetics ; Trinucleotide Repeats

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. ≥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.
Age of Onset ; Cohort Studies ; Deglutition Disorders ; Genetic Association Studies ; Genotype ; Humans ; Infant, Newborn ; Intensive Care, Neonatal ; Muscle Hypotonia ; Myotonic Dystrophy ; Myotonin-Protein Kinase ; Parturition ; Phenotype ; Prognosis ; Retrospective Studies ; Ventilators, Mechanical