Diagnosis Of Myotonic Dystrophy Research Articles

Acute leg pain and weakness in pregnancy: A new diagnosis of myotonic dystrophy

We present a unique case of a 44-year-old woman who presented at 29 weeks’ gestation with proximal limb pain and elevated creatine kinase. This occurred in the background of premature cataracts, atrial fibrillation and abnormal liver function. Clinical, pathological and neurodiagnostic findings supported a diagnosis of myotonic dystrophy, confirmed by genetic testing which revealed dystrophia myotonica protein kinase gene expansion. Muscle biopsy found both recent necrotising and chronic myopathic processes. Following delivery, the mother's myalgia resolved and creatine kinase quickly declined. The fetus was diagnosed with congenital myotonic dystrophy. We review the impact of myotonic dystrophy on pregnancy and discuss potential explanations for this patient's clinical course. This case emphasises the importance of considering myotonic dystrophy as a differential diagnosis in the right clinical context and the need for pre-pregnancy assessment and genetic counselling in women with known myotonic dystrophy.

Electrodiagnostic findings in myotonic dystrophy: A study on 12 patients.

Myotonic dystrophy (DM) is a complex multisystem disease with specific clinical and electrodiagnostic findings. Myotonia can be seen in the distal and proximal muscle groups in upper and lower limbs. There is no established guideline to demonstrate the sensitivity of muscles in the diagnosis of myotonic dystrophy. The aims of this study are to describe common electrodiagnostic findings in patients with DM; and to assess the electrodiagnostic sensitivity of muscles in the diagnosis of DM. In this retrospective study, patients’ age, sex, nerve conduction study findings including common upper and lower limbs nerve functions, and needle examination findings were collected and analyzed. A descriptive analysis (with percentage) was performed on the data obtained from the charts. NCS analysis showed more than half of patients had normal sensory and motor NCS findings. In 11 over 12 patients, sensory NCSs were within normal limits. Only one patient showed abnormal sensory responses. The most common abnormal NCS findings were decreased amplitude with normal latency and normal conduction velocity. The needle analysis showed distal muscles including first dorsal interosseous, abductor policies brevis, tibialis anterior, medial gastrocnemius and peroneal longus muscles are more sensitive in detecting myotonic discharges than proximal muscles including deltoid, triceps, vastus medialis and vastus lateralis. Our findings showed sensory nerve responses were usually within normal limits. The most common NCS abnormality showed decreased motor nerve amplitudes. The needle test showed myotonic discharges were more prominent in the distal muscles in upper and lower limbs.

Family communication following a diagnosis of myotonic dystrophy: To tell or not to tell?

Family communication about genetic information enables informed medical and reproductive decision-making. The literature suggests that a significant proportion of genetically at-risk family members remain uninformed about genetic risk information as a result of non-disclosure. This study explored the experiences of New Zealand families communicating about a diagnosis of type 1 myotonic dystrophy (DM1). Eligible individuals were identified and recruited from the New Zealand (NZ) MD Prev study, a nationwide study which aimed to determine the prevalence, impact, and costs of genetic muscle disorders across the lifespan. Twelve qualitative semi-structured interviews were conducted with 17 participants. The findings demonstrate diversity among and within families, with several distinct family narratives described. Most participants reported a motivation to tell relatives about their diagnosis to promote autonomy. Women were pivotal throughout communication processes and this was often tied to the concept of maternal responsibility and a desire to promote relatives' reproductive autonomy. The diagnosis of DM1 and the subsequent family communication decisions altered relationships for many, with both positive and negative impacts described. The findings demonstrate that individuals require time to explore the impact of a diagnosis of DM1 on self, family and intimate partner relationships to anticipate unique communication challenges. Genetic counselors can use these findings to inform their approach to counseling families with DM1. Longitudinal genetic counseling may be beneficial as a way to provide individuals with life stage specific support as they communicate with their relatives about a diagnosis of DM1.

Incidence and predictors of venous thromboembolism in inherited myopathies: A higher risk in myotonic dystrophy

The risk for venous thromboembolism (VTE) in inherited myopathies, which can lead to chronic immobilization, is unknown. To evaluate incidence of VTE in inherited myopathies, including for patients who lost ambulation, to compare it to incidence of VTE in general population and to identify predictors of VTE events in inherited myopathies. We retrospectively enrolled 2810 adult patients with genetically proven myopathy, admitted to our institutions between January 2000 and November 2014. We collected any information relative to their demographic and genetic characteristics, their muscular functional status including ambulation and the occurrence of VTE. We determined the incidence of venous thromboembolism in this population by using Kaplan–Meier product-limit method, compared it to general population with log-rank test and assessed its predictors with multivariable Cox modeling. Over a median follow-up of 8.5 years, 102 patients developed venous thromboembolism, representing a cumulative incidence of 6.2%, higher than in general population matched on age and sex. We identified four independent predictors of VTE: age (hazard-ratio ( HR ) = 1.02, 95%CI = 1.01–1.04, P = 0.002), a personal history of VTE ( HR = 5.54, 95%CI = 2.91–10.5, P < 0.0001), a diagnosis of myotonic dystrophy (DM) ( HR = 4.63, 95%CI = 2.63–8.18, P < 0.0001) and permanent loss of ambulation inpatients with DM ( HR = 4.07, 95%CI = 1.14–14.5, P = 0.030). Loss of ambulation alone was not a significant independent predictor of VTE. VTE in inherited myopathies is not a rare condition and is more frequent than in general population. We identified four independent predictors of VTE in these patients. Patients with DM represented the population with the highest risk of VTE.

Elevated level of creatinine phosphokinase in the blood of patients with peripheral polyneuropathies

Creatinine phosphokinase (CPK) elevated levels in blood are distinguished marker of neuromuscular diseases, especially myopathies, but can be found in great number of diseases as in hearth and brain tissue damages, some endocrine disturbances, malignant diseases, toxic and unwanted effects, febrile states, excessive motor activity. In inherited polyneuropathies, CPK levels are within normal values. Recently, hereditary peripheral sensomotor axonal, autosomal recessive polyneuropathy, associated with neuromyotonia (HINT1 polyneuropathy) has been recognized. Frequency and levels of hyper-CPK determination in HINT1 polyneuropatahy were examined in 31 patients (11 male/20 female), with HINT1 polyneuropathy and founder R37P mutation in HINT1gene. Elevated CPK levels (183–1170 IU/L) were found in HINT1 polyneuropathy patients. Levels >500 IU/L were found in generalized myothonia patients. Elevated CPK blood levels may be a direct consequence of electrophysiologically confirmed generalized neuromyotonia. Electromyography with nerve conduction study is very important for recognition of axonal polyneuropathy with neuromyotonia, in differential diagnosis of myotonic dystrophy and other myotonic disorders.

P273 Outcome after prolonged invasive mechanical ventilation in myotonic dystrophy

IntroductionPatients with myotonic dystrophy (MD) may present acutely with respiratory failure due to muscle weakness and aspiration pneumonia. We are not aware of published data regarding the outcome of intubation...

The maximal bite and hands grip force, in patients with molecular diagnosis of myotonic dystrophy

Objective. To investigate the condition of the masticatory muscles, evaluated by measuring the maximal bite and hands grip force, in patients with molecular diagnosis of myotonic dystrophy (MD) and to compare this with a matched group of healthy individuals.Study design. The bite and hands grip force of 34 patients with molecular diagnosis of MD were evaluated. An electronic dynamometer was employed for the bite force and a mechanical dynamometer for the hands grip force evaluation. For comparison among sides of the same group (related) Wilcoxon's proof and between the same side of different groups (independent) Mann-Whitney U test (α = 0.05) was used.Results. The mean bite force in the patient group was 127.5 N (both sides) and in the control group 441 N (both sides). Regarding the hands force, this was 59 N in the patient group (both sides) and 343 N on the right and 314 N on the left side in the control group.Conclusion. The bite and hands grip forces were significantly lower in the patient group when compared to the normal controls, without there being significant difference regarding gender, preferential side of mastication, or hands. The presence of the anticipation phenomenon was observed where the bite and hands grip forces were lower in subsequent generations of the same family. Objective. To investigate the condition of the masticatory muscles, evaluated by measuring the maximal bite and hands grip force, in patients with molecular diagnosis of myotonic dystrophy (MD) and to compare this with a matched group of healthy individuals. Study design. The bite and hands grip force of 34 patients with molecular diagnosis of MD were evaluated. An electronic dynamometer was employed for the bite force and a mechanical dynamometer for the hands grip force evaluation. For comparison among sides of the same group (related) Wilcoxon's proof and between the same side of different groups (independent) Mann-Whitney U test (α = 0.05) was used. Results. The mean bite force in the patient group was 127.5 N (both sides) and in the control group 441 N (both sides). Regarding the hands force, this was 59 N in the patient group (both sides) and 343 N on the right and 314 N on the left side in the control group. Conclusion. The bite and hands grip forces were significantly lower in the patient group when compared to the normal controls, without there being significant difference regarding gender, preferential side of mastication, or hands. The presence of the anticipation phenomenon was observed where the bite and hands grip forces were lower in subsequent generations of the same family.

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.

Prenatal diagnosis of congenital myotonic dystrophy and counseling of the pregnant mother: Case report and literature review

The molecular basis of the myotonic dystrophy (MD) kinase gene is expansion of the CTG repeat at the 3'-untranslated region of the MD gene. Variability of the CTG repeat size in different tissues of affected individuals has been demonstrated. The objective of this report was to examine and review the feasibility of prenatal diagnosis of congenital myotonic dystrophy (CMD) in pregnant women with MD using CTG repeat sizes in amniocytes or villi. We present a case of a pregnant woman with MD who underwent prenatal diagnosis of MD using amniocytes. The repeat size in the amniocytes was smaller than the repeat size in the maternal leukocytes and smaller than the repeat size in the infant blood. The infant had CMD. We also reviewed the literature for reports on MD cases that were prenatally tested for CTG repeat size using amniocytes or chorionic villi. Data were tabulated based on the number of maternal CTG repeats, prenatal procedure [amniocentesis or chorionic villus sampling (CVS)], CTG repeat size in fetal tissue, fetal/infant blood, and pregnancy outcome. Twenty-seven pregnancies at risk for MD that underwent prenatal diagnosis were reported. Eleven (40.7%) of the 27 pregnancies underwent amniocentesis, and 16 (59.3%) underwent CVS. Fourteen patients (61%) demonstrated an increase in CTG repeat size in the amniocytes or villi compared with the maternal repeat size. Nine (33%) of the 27 pregnancies were terminated because of CMD risk. The outcomes of 11 (40.7%) pregnancies were consistent with diagnosis of CMD. CMD was diagnosed in fetuses demonstrating expansion or contraction of the CTG mutation in the amniocytes. Prenatal diagnosis of MD is possible by using mutation analysis on maternal and fetal DNA and detection of the CTG repeat expansion. Prenatal diagnosis of CMD is more complex. The possible lack of correlation between CTG repeat size in amniocytes, villi, and other fetal tissues is a potential limitation in prenatal diagnosis and counseling of CMD using CTG repeat size. Thus, prenatal diagnosis of CMD should be based on a combination of factors, including maternal pregnancy history, clinical findings, and cautious interpretation of maternal and fetal DNA analysis.

Gastrointestinal symptoms in myotonic dystrophy.

Gastrointestinal complaints may be the initial symptom in myotonic dystrophy (MD). However, the frequency of gastrointestinal symptoms has never been prospectively evaluated. Forty patients with MD were interviewed with regard to their GI symptoms with a standardized questionnaire. A group of healthy subjects matched for age and sex served as controls. The most prevalent symptoms were abdominal pain (55%), dysphagia (45%), emesis (35%), chronic or episodic diarrhoea (33%), coughing while eating (33%), and anal incontinence (30%). Twenty-five per cent of the patients considered their GI problems to be the most disabling consequence of the disease, and 28% had GI problems that started before the diagnosis of MD. GI symptoms are common in patients with MD, may be the initial symptoms, and are often considered to be the most disabling consequence of the disease.

Persistent tunica vasculosa lentis as a sign of congenital myotonic dystrophy.

We describe the ocular findings in eight patients with congenital myotonic dystrophy in the newborn period. While three infants had normal findings, five infants had evidence of persistent tunica vasculosa lentis (TVL) at gestational ages ranging from 34 to 40 weeks. Atrophy of vessels on the anterior lens capsule is normally complete by 34 weeks gestation and its persistence should suggest congenital infection or congenital myotonic dystrophy. Diagnosis of myotonic dystrophy has serious implications for the baby and the mother, in whom the condition may have not been recognized earlier.

Myotonic Dystrophy Revealed at Videoradiography of Deglutition and Speech in Adult Patients with Velopharyngeal Insufficiency: Presentation of Four Cases

Patients with velopharyngeal insufficiency (VPI) without cleft palate, who appear for the first time in adulthood for treatment, will probably reveal a high percentage of undiagnosed myotonic dystrophy (MD). Videoradiography of deglutition and speech reveals the diagnosis. Eleven adult noncleft palate patients with VPI were studied with videoradiography of the pharynx and esophagus. Three exhibited functional radiographic manifestations of MD during deglutition and speech. The diagnosis confirmed by neurologic examination was not known or suspected prior to videoradiography. An additional patient with VPI and suspected MD displayed the same constellation of radiographic findings. Follow-up examinations confirmed the diagnosis of MD. Three of the four patients had had symptoms of VPI since childhood, but none had complaints of deglutition problems except for accidental nasal regurgitations.

The myotonic dystrophy gene.

The myotonic dystrophy gene codes for a protein kinase and contains a repeated trinucleotide motif (adenine-guanine-cytosine [AGC]) in its transcribed sequence. The repeat is polymorphic in the general population, varying in size from five to 37 AGC units in normal alleles. Myotonic dystrophy patients show expansions of the repeated sequence from over 50 elements up to several thousand units. There is a positive correlation between repeat size and clinical severity. The direct analysis of the AGC repeat size allows an easy confirmation of the clinical diagnosis of myotonic dystrophy in difficult cases and for prenatal counseling.

Myotonic dystrophy and traumatic quadriplegia: case report

A thirty-year-old man with traumatic quadriplegia, was also found to have weakness above the level of the injury. He had facial weakness, difficulty in swallowing, and recurrent respiratory problems. A diagnosis of myotonic dystrophy was supported by examination of his sister. The problems of diagnosis, and the implications of the diagnosis on the management of the patient with myotonic dystrophy and a spinal injury are discussed.

Usefulness of chromosome 19 RFLP haplotypes in the diagnosis of myotonic dystrophy

Three DNA probes (APOC2, PSC11, and LDR152) detecting RFLP polymorphisms were used to test the usefulness of the RFLP approach in myotonic dystrophy (MD) families from the isolated Finnish population. The informativeness of these polymorphisms did not differ from that reported in more mixed populations: in the 13 families of the study most of the 79 meiotic events studied were informative. One known recombinant is included in the study. The highest lod score obtained in the multilocus linkage analysis was z = 5.941 at recombination fraction theta = 0.02. The RFLP results significantly facilitated genetic counseling in problematic cases among the families studied. Although evidence could be found for linkage disequilibrium of the RFLP haplotypes formed in Finnish MD patients, our results do not exclude the possible existence of more than one ancient MD mutation in this population.

Congenital myotonic dystrophy: An often unsuspected cause of severe polyhydramnios

Two cases of severe polyhydramnios are presented in which the unsuspected diagnosis of myotonic dystrophy was made in the patient and the fetus.

Obstetric and neonatal complications of myotonic dystrophy

SummarySeven women delivered at the Simpson Memorial Maternity Pavilion between September 1987 and May 1989 were found to be suffering from the familial disorder, myotonic dystrophy. They experienced many of the classical obstetric and anaesthetic complications of the disease including hydramnios, preterm labour and post-anaesthetic apnoea. Three of the seven patients gave a history of previous neonatal death yet in only one of these three (and in two of the remaining four women) was the diagnosis of myotonic dystrophy made before the delivery reported here. We believe that the condition is underdiagnosed by obstetricians.

The secretor locus as a marker for prenatal prediction of myotonic dystrophy (DM).

To verify the reliability of secretor status for prenatal diagnosis of myotonic dystrophy (DM), 179 amniotic fluid samples were compared with saliva or urine samples of the infants by hemagglutination inhibition. While no discrepancies were observed, problems could arise with intermediate results. Additionally, secretor typing is only informative in 8.4% of patients.

Cardiac abnormalities in myotonic dystrophy: Electrocardiographic and echocardiographic findings in 65 patients and 34 of their unaffected relatives. Relation with age and sex and relevance for gene detection

Sixty-five patients with a definite diagnosis of myotonic dystrophy (MD) and 34 of their presumably unaffected relatives were examined cardiologically, including ECG in all and echocardiography in 61 and 32 persons respectively, in order to investigate the frequency of cardiac abnormalities, their clinical importance and their potential value as a preclinical marker in the diagnosis of MD. Atrioventricular conduction (AVC) abnormalities were found in 18 33 (54%) of affected males and in only 5 32 (16%) of affected females ( P = 0.0025). Intraventricular (IVC) conduction abnormalities were encountered with similar frequency in both sexes: in 12 33 (36%) of affected males and 10 32 (31%) of affected females. Mitral valve prolapses (MVP) were seen more often in affected females: 9 31 (29%) of affected males vs 15 30 (50%) of affected females have MVP ( P = 0.16). A previously undescribed finding was that of pericardial effusions in 5 affected and in 1 unaffected person. All affected males with MVP also had conduction abnormalities, but cardiac findings were not interrelated otherwise. None of the cardiac abnormalities mentioned were age-related. Only 8 65 (12%) of patients had cardiac symptoms, all of which were the result of conduction defects. As far as can be judged from a transversal study, the value of cardiac examination of this kind as a preclinical test for the diagnosis of MD is modest. It is argued that IVC-abnormalities, but not AVC-disturbances or MVP, in clinically unaffected relatives may indicate that they are preclinical heterozygotes. The significance of pericardial effusion for the diagnosis of MD awaits further evaluation.

The use of apolipoprotein CII as a genetic marker for myotonic dystrophy.

In five families we have confirmed the close linkage between the genes for myotonic dystrophy and apolipoprotein CII. The total maximum lod (log of the odds) score was 3.32 at 0 recombination. We demonstrate that the use of a Ban I restriction site polymorphism for apolipoprotein CII adds additional useful information when combined with the more commonly used Taq I polymorphism. The potential practical clinical use of these markers for the prenatal diagnosis of myotonic dystrophy is demonstrated.