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.

Expresión clínica de distrofia miotónica congénita / Clinical expression of congenital myotonic dystrophy

Introducción: La distrofia miotónica congénita es la forma clínica que produce la expresión fenotípica más grave, con alta morbilidad y mortalidad en los primeros meses de vida, dadas fundamentalmente por las complicaciones respiratorias. Objetivo: Describir una serie de casos con expresión clínica de distrofia miotónica congénita. Presentación de casos: La serie estaba conformada por cuatro pacientes con diagnóstico de la enfermedad en la provincia de Pinar del Río, Cuba. El estudio se realizó entre: enero de 2015-diciembre de 2019. Se revisaron las características clínicas, epidemiológicas y genéticas de la entidad. Se analizaron los antecedentes prenatales-perinatales de cada caso, las manifestaciones fenotípicas, los antecedentes familiares y el cálculo de la prevalencia. En el 100 por ciento de los casos se presentó parto pretérmino con depresión neonatal severa e hipotonía. Entre los antecedentes prenatales se describió la disminución de los movimientos fetales y el polihidramnios en el 75 y 50 por ciento de los casos, respectivamente. La totalidad de los pacientes eran descendientes de madres afectadas. Las principales complicaciones que condujeron a morbilidad y mortalidad en el 100 por ciento de los casos fueron las relacionadas con el sistema respiratorio, trastornos hidroelectrolíticos y las infecciones asociadas. Conclusiones: En el período neonatal son importantes los antecedentes prenatales-perinatales de los pacientes con distrofia miotónica. Estos antecedentes, constituyen acontecimientos que forman parte de la secuencia de hipoquinesia fetal dada por la afectación neuromuscular intraútero. Los antecedentes familiares y sobre todo cuando la madre está afectada conducen a expresiones severas en la descendencia(AU)

Introduction: Congenital myotonic dystrophy is a clinical form that produces the most severe phenotypic expression, with high morbility and mortality in the first months of life mainly due to respiratory complications. Objective: To describe a serie of cases with clinical expression of congenital myotonic dystrophy. Cases presentation: The serie was formed by 4 patients with diagnosis of the disease in Pinar del Río province, Cuba. The study was made from January, 2015 to December, 2019. There were reviewed the clinical, epidemiological and genetic characteristics of this entity. There were analyzed prenatal and perinatal backgrounds of each case, phenotypic manifestations, the family records and the prevalence calculations. In 100 percent of the cases it was presented preterm birth with severe neonatal depression and hypotonia. Among the prenatal backgrounds, it was described the decrease of the fetal movements and polyhydramnios in the 75 and 50 percent of the cases, respectively. All the patients were descendants of affected mothers. The main complications that led to morbility and mortality in 100 percent of the cases were the ones related with the respiratory system, hydrolectrolitic disorders and associated infections. Conclusions: In the neonatal period are important the prenatal-perinatal records of patients with myotonic dystrophy. This background shows events that are part of the fetal hypokinesia´s sequence caused by intrauterine neuromuscular affectation. Family background and especially when the mother is affected lead to severe expressions in the descendants(AU)

Prepubertal gynecomastia: a rare manifestation of myotonic dystrophy type 1 / Ginecomastia pré-púbere: uma manifestação rara da distrofia miotônica tipo 1

ABSTRACT Objective: To present a case of bilateral gynecomastia in a prepubertal boy with autism spectrum disorder, diagnosed with myotonic dystrophy type 1. Case description: A 12-year-old boy with autism spectrum disorder presented at a follow-up visit with bilateral breast growth. There was a family history of gynecomastia, cataracts at a young age, puberty delay, and myotonic dystrophy type 1. The physical examination showed that he had bilateral gynecomastia with external genitalia Tanner stage 1. Neurologic examination was regular, without demonstrable myotonia. The analytical study revealed increased estradiol levels and estradiol/testosterone ratio. After excluding endocrine diseases, the molecular study of the dystrophia myotonica protein kinase gene confirmed the diagnosis of myotonic dystrophy type 1. Comments: A diagnosis of prepubertal gynecomastia should include an investigation for possible underlying diseases. This case report highlights the importance of considering the diagnosis of myotonic dystrophy type 1 in the presence of endocrine and neurodevelopmental manifestations.

RESUMO Objetivo: Apresentar o caso de um adolescente pré-púbere com ginecomastia bilateral e transtorno do espectro autista, diagnosticado com distrofia miotônica tipo 1. Descrição do caso: Adolescente do sexo masculino de 12 anos, com transtorno do espectro autista, observado em consulta de seguimento por crescimento mamário bilateral. O paciente tinha antecedentes familiares de ginecomastia, catarata em idade jovem, atraso pubertário e distrofia miotônica tipo 1. À observação física, apresentava ginecomastia bilateral estádio 1 de Tanner. O exame neurológico era normal, sem miotonia aparente. O estudo analítico mostrou níveis elevados de estradiol e da relação estradiol/testosterona. Após exclusão de causas endócrinas, o estudo molecular do gene DMPK confirmou o diagnóstico de distrofia miotônica tipo 1. Comentários: Perante um quadro de ginecomastia pré-púbere, deve-se excluir doenças subjacentes. Este caso reforça a importância de considerar o diagnóstico de distrofia miotônica tipo 1 na presença de manifestações endócrinas e do neurodesenvolvimento.

Cardiodesfibrilador implantável na prevenção de morte súbita em paciente com distrofia muscular tipo 1 (doença de Steinert) / Implantable cardiac defibrillator for sudden death prevention in myotonic dystrophy type 1 (Steinert disease)

A distrofia muscular tipo 1 é uma miopatia hereditária genética com alto risco de morte súbita. Como a morte súbita é um evento comum, existe o desafio de identificar o paciente de maior risco para considerar a colocação de um cardiodesfibrilador implantável. O presente estudo relata o caso de um paciente com distrofia muscular tipo 1 com marcadores de alto risco para morte súbita, no qual foi implantado um cardiodesfibrilador implantável com sucesso. A correta estratificação para morte súbita é um importante passo na indicação do cardiodesfibrilador implantável

Myotonic dystrophy type 1 is a genetic and hereditary myopathy associated to a high risk of sudden death. As sudden death is a relatively common event, it is a challenge to identify those patients with highest risk to consider the use of an implantable cardiac defibrillator. The present case report describes a myotonic dystrophy type 1 patient with risk factors for sudden death in whom an implantable cardiac defibrillator was successfully implanted. The correct risk stratification for sudden death is an important step for the indication of an implantable cardiac defibrillator

Distrofia miotônica de Steinert e hipersonia primária: relato de caso / Myotonic dystrophy of Steinert and primary hypersomnia: case report

Este artigo apresenta o caso de uma paciente com distrofia miotônica tipo 1 (DM1) (doença de Steinert) e faz a revisão de literatura sobre sonolência excessiva diurna (SED) nestes pacientes. Paciente de 36 anos, portadora de (DM1), apresenta SED e testes múltiplos de latência com média de latências de 1 minuto e 22 segundos. DM1 e SED podem ter várias etiologias, a ressaltar as devidas à disfunção no sistema nervoso central ou à miopatia. No caso da paciente, provavelmente predomina a SED de origem central.

This article presents the case of a myotonic dystrophy type 1 - Steinert's disease (DM1) patient and reviews the literature on excessive daytime sleepiness (EDS) in these patients. Patient of 36 years of age, with DM1, presents EDS and mean multiple sleep latency test of 1 minute and 22 seconds. DM1 and EDS can have some etiologies, mainly due to central nervous system dysfunction or to the myopathy. In the present case, probably predominate the SED of central origin.

Disabilities caused by unstable mutations in Costa Rica

Myotonic dystrophy and fragile X syndrome are two genetically determined relatively common disabilities. Both are examples of a new type of mutation mechanism called unstable or dynamic mutations, triple repeats expansions or DNA amplification. Fragile X syndrome is recognized as the main cause of hereditary mental retardation and myotonic dystrophy is considered the most common muscular dystrophy of adults. This is a prospective non randomized study of clinically affected people, in order to confirm the diagnosis with molecular techniques (Southern blot and PCR) and to perform cascade screening of the rest of the family to offer them adequate genetic counseling. We were able to corroborate the initial diagnosis in most clinical cases of myotonic dystrophy, but in the cases of mental retardation more than half studies were negative for fragile X syndrome, stressing the difficulties encountered by medical practitioners to diagnose this syndrome. The reasons for this are several; probable the main culprit is the subtle and unspecific clinical picture affected individuals exhibit, particularly children before puberty. Cascade screening, genetic counseling and selective abortion are the only tools available to prevent these disabling diseases for the moment.

Electrophysiological evaluation in myotonic dystrophy: correlation with CTG length expansion

In myotonic dystrophy (MD), disease severity has been correlated with expansion of CTG repeats in chromosome 19. The aims of this study were to evaluate efficacy of electromyography in the diagnosis of MD, access the frequency and the characteristics of peripheral involvement in the disease and to verify whether the CTG repeats correlated with the electrophysiological abnormalities. Twenty-five patients and six relatives at risk of carrying the MD gene were examined. Electrical myotonia (EM) was scored. Sensory and motor conduction velocity (CV) were studied in five nerves. Leukocyte DNA analysis was done in 26 subjects. Myopathy and myotonia were found in 27 cases. EM was most frequent in muscles of hand and in tibialis anterior. No significant correlation was found between EM scores and length of CTG expansions. EM scores correlated significantly with the degree of clinical myopathy, expressed by a muscular disability scale. Peripheral neuropathy was found in eight subjects and was not restricted to those who were diabetics

Correlation of clinical profile of myotonic dystrophy with CTG repeats in the myotonin protein kinase gene.

The molecular genetic analyses (PCR and Southern hybridization) of Indian patients with myotonic dystrophy (DM) were carried out to determine the degree of repeat expansion and an attempt was made to correlate the repeat number with disease severity. A scoring system based on the salient clinical features was devised to objectively assess the disease severity. The repeat expansion was seen in 11 of 12 patients examined and showed an inverse correlation with the age of onset confirming the phenomenon of anticipation. This was further established in the two pedigrees studied, clearly demonstrating both clinical and genetic anticipation. The clinical severity score, however, did not correlate well with the repeat number. Nonetheless, such molecular genetic analyses may have immense value as a screening procedure to identify premutations as well as in prenatal diagnoses.

Distrofia miotónica congénita / Congenital myotonic dystrophy

La distrofia miotónica es una patología que afecta tanto al músculo como a otros tejidos y órganos. Su etiología es genética, con una forma de herencia autosómica dominante y se caracteriza por presentar dos formas clínicas bien diferenciadas: la clásica del adulto y la congénita. Esta última, de pronóstico severo, ocurre únicamente en hijos de mujeres afectadas y sería una de las causas más frecuentes de hipotonía neonatal. Se presentan siete pacientes recién nacidos con distrofia miotónica congénita, se mencionan los mecanismos genéticos moleculares involucrados y se enfatiza la importancia del diagnóstico clínico de esta patología, a descartar en todo recién nacido hipotónico, sobre todo en casos de madres con escasa sintomatología.

large iranian family with myotonic dystrophy

We report on the first observation of an Iranian family with myotonic dystrophy [Steinert disease]. The proband was 26 years old and had suffered a long history of progressive myotonia and muscular weakness. He presented with frontal baldness, ptosis, bilateral facial weakness, unclear speech, and mental retardation. The disease onset was probably at birth. The diagnosis was made by detection of a large expansion of the CTG repeat in the DM Protein kinase gene [DMPK] on chromosome 19. In the proband's family, there were at least 11 affected members in three generations. There is clear evidence of anticipation as the disease manifested itself earlier in successive generations with increasing severity associated with gains of repeat sizes on transmission from parent to offspring. The chromosomal background of this mutation corresponded to the background of other DM mutations in the European population

Avaliaçäo orofacial através de uma escala de pontuaçäo em pacientes com distrofia miotônica (doença de Steinert) / Orofacial evaluation through a punctuation scale in patients with myotonic dystrophy (Steinert's disease)

Foi aplicado o exame orofacial em um grupo de 39 pacientes com distrofia miotônica através de uma tabela original de pontuaçäo. O grupo apresentou queda de 43,70 por cento em relaçäo ao normal. O desempenho do grupo em que a doença foi transmitida pela mäe foi 4,15 por cento superior ao de transmissäo paterna. Na análise dos grupos separados por sexo e pareados pela mesma idade na época do exame, o feminino foi 6,16 por cento superior ao masculino. Nos grupos separados por transmissor do gene, quando o pareamento se deu pelo mesmo tempo de doença, o grupo de transmissäo materna obteve percentual 3,63 superior ao da paterna. Porém, quando considerados apenas os que já nasceram doentes, o sexo masculino alcançou 3,91 por cento a mais que o feminino e o da herança materna superou o da paterna em 9,52 por cento. Na investigaçäo dos grupos separados por décadas, quando considerada a idade de início dos sintomas, houve tendência a aumento do percentual à medida que as décadas iam se sucedendo. Quando enfocada a idade do paciente ao ser examinado, houve relativa estabilidade no desempenho e, quando considerado o tempo de doença, o percentual diminuiu da 1a. para a 2a. década de 10,68 por cento, com tendência a estabilizaçäo a partir de entäo. Isto sugeriu que, fonoaudiologicamente, a doença é menos intensa nos pacientes cujos sintomas näo se iniciaram no nascimento, têm menos de 10 anos de tempo de doença e início mais tardio dos sintomas

Distrofia miotônica: estudo da correlaçäo clínico-genética em um par familiar (pai-filho) / Myotonic dystrophy: study of clinical-genetic correlation in a familial pair

É relatado o caso de um paciente com início da sintomatologia aos 7 anos de idade, cujo estudo genético e o de seu pai, portador assintomático, revelou um fragmento adicional de DNA, maior no paciente sintomático do que no pai portador. Os dados proveniente do estudo genético deste par familiar em geraçöes sucessivas, provavelmente o primeiro realizado no Brasil desde a recente descoberta por autores americanos do tipo de anormalidade genética presente na distrofia miotônica, vêm salientar a explicaçäo genética para o fenômeno clínico da antecipaçäo. Säo comentados resumidamente os principais avanços no campo da genética molecular desta doença e sua correlaçäo ao início precoce da sintomatologia, como ocorreu no nosso paciente

O impacto da biologia molecular na compreensåo e prevençåo das miopatias hereditárias / Biological molecular impact in comprehension and prevention of hereditary myopathies

Dentre as quase 6.000 doenças genéticas já identificadas, a maioria såo diagnosticadas em hospitais pediátricos ou em ambulatórios de neurologia. Até recentemente, o diagnóstico era baseado em exame clínico e exames complementares mas pouco se conhecia acerca das causas primárias responsáveis por estas patologias. A introduçåo das novas técnicas de biologia molecular, em particular, a localizaçåo de genes deletérios e a identificaçåo de seus produtos têm trazido avanços enormes na compreensåo dos mecanismos que causam estas doenças, o que tem sido fundamental para a sua prevençåo (através da identificaçåo de portadores em risco e diagnóstico pré-natal) e futuros tratamentos

The impact of molecular biology for the understanding and prevention of hereditary myopathies in the Brazilian population

The localization and cloning of the gene resposible for Duchenne/Becker muscular dystrophy followed by the identification of its product brought great advances to the field of muscular dystrophies. More recently, other genes responsible for other forms of muscular dystrophies have been identified such as: limb-girdle muscular dystrophy, facioscapulohumeral muscular dystrophy and myotonic dystrophy. Our group has already studied over 9,000 individuals belonging to families with patients affected by different forms of hereditary myopathies. In this article we are illustrating how the introduction of molecular biology technology improved clinical and differential diagnosis, the preventionnn of new cases (through identification of carriers and prenatal diagnosis) and the comprehension of the underlying pathological mechanisms which will be fundamental for future treatments based on gene therapy.

Família com predominância do comprometimento cardíaco na doença de Steinert / Family with predominance of cardiac involvement in Steinert's disease

Estudaram-se mäe e dois filhos em que se diagnosticou doença de Steinert. A mäe, com 49 anos de idade, apresentava o envolvimento neuromuscular; atrofia muscular miotônica em face, pescoço e extremidades distais; e recebeu um marcapasso definitivo por 2 episódios sincopais e exame radiológico que evidenciava ECG com P-R de 250ms, QRS de 130ms com BRE e EEF evidenciando intervalos AH de 140ms PRE do NAV de 590ms, ponto de Wenckebach de 115 bpm, e intervalo HV de 80ms antes e 95ms após estresse pela procainamida. Em funçäo do caráter hereditário autossômico dominante com relativa raridade de manifestaçöes cardíacas täo evidentes (relata-se até 80%de alteraçöes eletrocardiográficas, mas menos de 15%com sintomas), procedeu-se à avaliaçäo de seus 2 filhos (F1 e F2): F1 (masc., 31 anos) com P-R de 180ms e QRS de 100ms; e F2 (fem., 27 anos) com P-R de 200ms e QRS de 100ms; ambos com HBAE. Os ecocardiogramas foram normais eo holter evidenciou bradicardia acentuada em ambos e BRE intermitente FC dependente (fase 3) em F2. O EEF revelou: F1 e F2 com funçäo AV normal; F1 com HV de 70ms antes e após procainamida e F2 com 80ms antes e 130ms após...

Distrofia miotônica na infância: relato de caso

Os autores relatam dosi casos de distrofia miotônica que tiveram início desde o nascimento e responderam favoravelmente ao uso do bloqueador de cálcio