Clinical and genetic characteristics of myotonic dystrophy type 1(report of one family) / 临床神经病学杂志

Objective To investigate the clinical and genetic characteristics of myotonic dystrophy type 1(DM1).Methods A DM1 patient and his family members admitted to the First Affiliated Hospital of Soochow University in May 2023 were examined by physical examination,EMG,muscle biopsy and genetic detection,and the family pedigree was drawn to analyze the clinical characteristics and genetic manifestations of the patients.Results There were 9 members in this family,2 of whom were suffering from DM1,and there was a phenomenon of genetic anticipation.Both patients with DM1 had typical symptoms such as myotonia and myasthenia,accompanied by involvement of multiple systems such as the central nervous system,heart,and endocrine system.The electromyogram showed characteristic myotonic potentials.Muscle biopsy of the proband showed typical myotonic dystrophy with rimmed vacuoles.Genetic detection found that their DMPK genes both had a large number of CTG trinucleotide repeat expansions.Oxcarbazepine treatment is effective.Conclusions DM1 is a genetic disease with typical symptoms of myotonia and myasthenia gravis,accompanied by involvement of central nervous system,heart,endocrine and other systems.Electromyography,muscle biopsy and gene detection can help to diagnose DM1.Rimmed vacuoles are rare in muscle pathology.Oxcarbazepine can improve the symptoms of myotonia.

A case of early onset diabetes with myotonic dystrophy type 1 / 中南大学学报(医学版)

Myotonic dystrophy type 1 (DM1, OMIM 160900) is a rare autosomal dominant hereditary disease. A case of DM1 patient with early onset diabetes and decreased muscle strength was treated in the Department of Endocrinology, Third Xiangya Hospital, Central South University. The peripheral blood of the patient was collected to extract DNA for gene detection. It was found that the triple nucleotide CTG repeat in the 3'-untranslated region (3'-UTR) of the dystrophia myotonica protein kinase (DMPK) gene was more than 100 times, and the diagnosis of DM1 was clear. For diabetes patients with multiple system abnormalities such as muscle symptoms, attention should be paid to the screening of DM1, a rare disease.

Clinical and genetic characteristics of two families with myotonic dystrophy type I / 中华神经医学杂志

Objective:To investigate the clinical and genetic characteristics of families with myotonic dystrophy type I.Methods:Two families with myotonic dystrophy type I admitted to Department of Neurology, First Affiliated Hospital of He'nan University of Science and Technology in September and October 2021 were chosen; their clinical data were retrospectively analyzed. The muscle pathological changes were confirmed by electromyography and muscle MRI. Repeat-primed PCR assay was used to detect the number of CTG repeats in the 3' end non-coding region of DMPK gene. Results:Clinical heterogeneity existed among the two families of patients; muscle weakness and muscular atrophy of the skeletal muscle were the main clinical manifestations; limb weakness, axe face, percussion myotonia and myoglobular sign were noted; systemic multi-system symptoms included palpitation and chest tightness, cataracts, gastrointestinal symptoms, fatigue/lethargy, and cognitive impairment. Electromyography showed myotonic potential and myogenic damage. Muscle fatty infiltration and atrophy were noted in muscle MRI, and lesions were predominantly in the gastrocnemius. All patients had abnormal amplification of DMPK gene CTG (number of CTG repeats> 50 or 100). Conclusion:In addition to skeletal muscle involvement, systemic multi-system involvement such as cardiac, eye, respiratory, endocrine, and nervous system should also be noted by clinicians in patients with myotonic dystrophy type I.

Genotype-phenotype correlations in pediatric patients with myotonic dystrophy type 1 / 소아과

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.

Myotonic dystrophy type 1: frequency of ophthalmologic findings / Distrofia miotônica tipo 1: frequência dos achados oftalmológicos

ABSTRACT The purpose of the study was to evaluate the frequency of ophthalmologic abnormalities in a cohort of myotonic dystrophy type 1 (DM1) patients and to correlate them with motor function. We reviewed the pathophysiology of cataract and low intraocular pressure (IOP). Method Patients were included after clinical and laboratory diagnosis and after signed informed consent. They were evaluated by Motor Function Measure scale, Portuguese version (MFM-P) and ophthalmic protocol. Results We evaluated 42 patients aged 17 to 64 years (mean 40.7 ± 12.5), 22 of which were men. IOP (n = 41) was reduced in all but one. We found cataract or positivity for surgery in 38 (90.48%) and ptosis in 23 (54.76%). These signs but not IOP were significantly correlated with severity of motor dysfunction. Abnormalities in ocular motility and stereopsis were observed. Conclusion Cataract and ptosis are frequent in DM1 and associated to motor dysfunction. Reduced IOP is also common, but appears not to be related with motor impairment.

RESUMO O objetivo do estudo foi avaliar a frequência das anormalidades oftalmológicas em uma coorte de pacientes com distrofia miotônica tipo 1 (DM1) correlacionando-as à função motora. Revisamos a fisiopatogenia da catarata e baixa pressão intraocular (PIO). Método Os pacientes foram incluídos após diagnóstico clínico-laboratorial de DM1. Aqueles que assinaram o termo de participação foram avaliados pela escala medida da função motora, versão em português (MFM-P) e protocolo oftalmológico. Resultados Avaliamos 42 pacientes de 17 a 64 anos (média 40,7 ± 12,5), 22 do sexo masculino. Encontramos catarata ou positividade de cirurgia em 38 (90,48%) e blefaroptose em 23 (54,76%) e esses sinais foram correlacionados significativamente à maior gravidade da disfunção motora. Baixa PIO também foi comum e não correlacionada à gravidade motora. Alterações da motilidade ocular e de estereopsia ocorreram. Conclusão Catarata e ptose palpebral são frequentes na DM1 e associadas à gravidade motora. Baixa PIO é comum e parece ser independente da evolução motora.

Distrofa miotónica congénita en una Unidad de Cuidados Intensivos Neonatales: serie de casos / Congenital myotonic dystrophy in a Neonatal Intensive Care Unit: case series

La distrofia miotónica de Steinert es una enfermedad multisistémica, autosómica dominante, con un amplio espectro de gravedad y manifestaciones clínicas. La forma más grave es aquella que se manifesta en el periodo neonatal, llamada distrofa miotónica congénita. Se destaca la hipotonía global al nacer y el compromiso de la función respiratoria. Las complicaciones son frecuentes, principalmente, retraso del desarrollo psicomotor, del crecimiento pondoestatural, difcultades alimentarias y constipación. Se asocia a un mal pronóstico, con una mortalidad global de hasta un 50% de los niños gravemente afectados. Presentamos cinco casos de distrofa miotónica congénita con el objetivo de describir manifestaciones clínicas, métodos diagnósticos, tratamiento y pronóstico. Los datos existentes en la literatura sobre el desarrollo psicomotor, complicaciones y pronóstico de los supervivientes con distrofa miotónica congénita son pocos. En nuestra serie de casos, las limitaciones psicomotoras presentadas son signifcativas.

Steinert myotonic dystrophy is a multisystemic disease, autosomal dominant, with a wide spectrum of severity and clinical manifestations. The most severe form is one that manifests in the neonatal period, called congenital myotonic dystrophy. This condition is distinguished by overall hypotonia at birth and respiratory function compromise. Complications are frequent, mainly psychomotor development delay, growth failure, food diffculties and constipation. It is associated with a poor prognosis, with an overall mortality of up to 50% of severely affected children. We present fve patients with congenital myotonic dystrophy in order to describe clinical manifestations, diagnosis, treatment and prognosis. Existing data in the literature on psychomotor development, complications and prognosis of survivors withcongenital myotonic dystrophy are scarce. In our case studies, we have found signifcant chronic psychomotor limitations.

Clinical characteristics of a family with myotonic dystrophy type 1 / 中华神经医学杂志

Objective To explore the clinical features of a family with myotonic dystrophy type 1 (DM1) in order to improve the knowledge of this disease.Methods Clinical data of members from the family were collected.Electrocardiogram (ECG),electromyogram (EMG) and blood biochemistry were performed in some members of the family.Characteristics of pathology and gene of the propositi were detected.Results Anticipation was found in the family which was verified as DM1.In the all 19 patients,17 had myasthenia gravis,14 had muscle atrophy,16 had myotonia,5 had complicated with cataract,and 7 had complicated with hypophrenia.The 5 patients accepted ECG all had abnormal results,3 of them had myotonic discharge and metabolic abnormalities.Pathological analysis showed the main fibers atrophy was type Ⅰ,and the protein dystrophin expression was completely in the propositi.Conclusions The clinical manifestations of patients are various.DM1 affects eye (the lens),heart (mainly the conduction system),reproductive system besides skeletal muscle.Necessary auxiliary examinations and regular follow-up should be performed to evaluate and deal with multisystemic involvement in DM1 patients.EMG and pathological results are helpful in the diagnosis.Gene analysis can verify the disease and identify subclinical patients.

Cognitive changes and cranial MRI changes in patients with myotonic dystrophy type 1: a study of 4 cases / 中华神经医学杂志

Objective To investigate the cognitive, intelligent and cranial MRI status of 4 patients with myotonic dystrophy type 1 (DM1). Methods A pedigree of 4 patients,admitted to our hospital from September 2011 to December 2011 and diagnosed as having DM1, were chosen in our study; Chinese edition tests of Wechsler adult intelligence scale and Wechsler memory scale were used to test the intelligence of these patients; Montreal cognitive assessment (MoCA) and Neurobehavioral cognitive status examination (NCSE) were applied to evaluate the patients' cognitive function.All of the 4 patients received a cranial MRI scan. Results Except for 1 patient,the other 3 patients had low intelligent quotient (IQ) and memory quotient (MQ),and their verbal IQs were all lower than performance IQs.Three patients showed impaired visual space/executive skills,calculation,memory,and conceptual thinking abilities; 1 patient showed impaired sentence repetition and verbal fluency on MoCA,though his final scores were within normal range. Three patients had brain atrophy to some extent on MRI scan,prominently in the frontal lobe and temporal lobe; white matter lesions and thickened skull were founded in all 4 patients. Conclusion Multiple cognition disorders and brain involvements can be found in DM1 patients and deserve further investigation.

Molecular and Clinical Characteristics of Myotonic Dystrophy Type 1 in Koreans / 대한진단검사의학회지

BACKGROUND: Myotonic dystrophy type 1 (DM1) is an autosomal-dominant muscular dystrophy caused by expansion of cytosine-thymine-guanine (CTG) trinucleotide repeats in the myotonic dystrophy protein kinase (DMPK) gene. The clinical features of DM1 are multisystemic and highly variable, and the unstable nature of CTG expansion causes wide genotypic and phenotypic presentations. The aim of this study was to characterize the molecular and clinical spectra of DM1 in Koreans. METHODS: The CTG repeats of 283 Korean individuals were tested by PCR fragment analysis and Southern blot. The following characteristics were assessed retrospectively: spectrum of CTG expansions, clinical findings, genotype-phenotype correlation, anticipation, and genetic instability. RESULTS: One-hundred twenty-four patients were confirmed as DM1 by molecular tests, and the CTG expansions ranged from 50 to 2,770 repeats (median 480 repeats). The most frequent clinical features were myotonia, muscular weakness, and family history. Patients with muscular weakness or dysfunction of the central nervous system harbored larger CTG expansions than those without each symptom (P<0.05). The age of onset was inversely correlated with the size of the CTG expansion (gamma=-0.422, P<0.001). The instability of CTG expansion representing as the maximum difference between sibships was observed from 50 to 700 repeats in nine families. Clinical anticipation and the increase in CTG repeat were significantly higher in maternally transmitted alleles (P=0.002). CONCLUSIONS: Molecular genetic tests are not only essential for diagnosis, but also helpful for suggesting the spectrum and relationship between genotype and phenotype in Korean DM1 patients.