Cytosine-thymine-guanine Research Articles

Hypogammaglobulinemia and infection risk in myotonic dystrophy type 1.

Hypogammaglobulinemia is a common yet under-recognized feature of myotonic dystrophy type 1 (DM1). The aims of our study were to determine the frequency of immunoglobulin G (IgG) deficiency in our cohort, to examine the association between immunoglobulin levels and cytosine-thymine-guanine (CTG) repeat length in the DMPK gene, and to assess whether IgG levels are associated with an increased risk of infection in DM1 patients. We conducted a single-center, retrospective cross-sectional study of 65 adult patients with DM1 who presented to the Neuromuscular Clinic at Concord Repatriation General Hospital, Sydney, Australia, between January 2002 and January 2022. We systematically collected and analyzed clinical, laboratory, and genetic data for all patients with available serum electrophoresis and/or IgG level results. Forty-one percent of DM1 patients had IgG deficiency despite normal lymphocyte counts, IgA, IgM, and albumin levels. There was an association between CTG repeat expansion size and the degree of IgG deficiency (F = 6.3, p = .02). There was no association between IgG deficiency and frequency of infection in this group (p = .428). IgG deficiency is a frequent occurrence in DM1 patients and is associated with CTG repeat expansion size. Whether hypogammaglobulinemia is associated with increased infection risk in DM1 is unclear. A prospective multicenter cohort study is needed to evaluate this.

Role of descemet's stripping without keratoplasty in management of endothelial disease.

To summarize recent literature on Descemet's stripping only (DSO) in management of endothelial disease with particular focus on Fuchs endothelial corneal dystrophy (FECD). DSO is currently indicated in patients with early FECD, central guttae, and preserved peripheral corneal endothelial cell (CEC) count. Time to corneal clearance may be accelerated and maintained with addition of topical rho-kinase inhibitor (ROCKi). There are reports describing successful use of DSO to treat endothelial disease due to iatrogenic trauma. In patients with transcription factor 4 gene mutation, increased cytosine, thymine, guanine (CTG) triplet repeat load may be associated with DSO failure risk. Emerging pharmacotherapies and cell-suspension treatments may improve procedure effectiveness and expand clinical indications. DSO can be used as the initial surgical treatment in management of symptomatic endothelial disease due to FECD where peripheral CEC function appears preserved. Stand-alone DSO or DSO combined with cataract surgery is effective and postoperative topical ROCKi supplementation will improve time to corneal clearance and CEC count.

Subjective-objective sleepiness discrepancy in adult-onset myotonic dystrophy type 1.

Subjective-objective sleepiness discrepancy in adult-onset myotonic dystrophy type 1.

TCF4 trinucleotide repeat expansion in Swedish cases with Fuchs' endothelial corneal dystrophy.

Fuchs' endothelial corneal dystrophy (FECD) has been considered a genetically heterogeneous disease but is increasingly associated with the transcription factor 4 (TCF4) gene. This study investigates the prevalence of the cytosine-thymine-guanine (CTG)n repeat expansion in TCF4 among FECD patients in northern Sweden coupled to the phenotype. Blood samples were collected from 85 FECD cases at different stages. Short tandem repeat PCR and triplet repeat-primed PCR were applied in order to determine TCF4 (CTG)n genotype. A (CTG)n repeat expansion (n > 50) in TCF4 was identified in 76 of 85 FECD cases (89.4%) and in four of 102 controls (3.9%). The median (CTG)n repeat length was 81 (IQR 39.3) in mild FECD and 87 (IQR 13.0) in severe FECD (p = 0.01). A higher number of (CTG)n repeats in an expanded TCF4 allele increased the probability of severe FECD. Other ocular surgery was overrepresented in FECD cases without a (CTG)n repeat expansion (44.4%, n = 4) compared with 3.9% (n = 3) in FECD cases with an (CTG)n repeat expansion (p < 0.001). In northern Sweden, the FECD phenotype is associated with (CTG)n expansion in the TCF4 gene, with nearly 90% of patients being hetero- or homozygous for (CTG)n expansion over 50 repeats. Furthermore, the severity of FECD was associated with the repeat length in the TCF4 gene. Ocular surgery might act as an environmental factor explaining the clinical disease in FECD without a repeat expansion in TCF4.

Preliminary Findings on CTG Expansion Determination in Different Tissues from Patients with Myotonic Dystrophy Type 1.

Myotonic Dystrophy type 1 (DM1) is characterized by a high genetic and clinical variability. Determination of the genetic variability in DM1 might help to determine whether there is an association between CTG (Cytosine-Thymine-Guanine) expansion and the clinical manifestations of this condition. We studied the variability of the CTG expansion (progenitor, mode, and longest allele, respectively, and genetic instability) in three tissues (blood, muscle, and tissue) from eight patients with DM1. We also studied the association of genetic data with the patients’ clinical characteristics. Although genetic instability was confirmed in all the tissues that we studied, our results suggest that CTG expansion is larger in muscle and skin cells compared with peripheral blood leukocytes. While keeping in mind that more research is needed in larger cohorts, we have provided preliminary evidence suggesting that the estimated progenitor CTG size in muscle could be potentially used as an indicator of age of disease onset and muscle function impairment.

Three-dimensional imaging in myotonic dystrophy type 1: Linking molecular alterations with disease phenotype.

ObjectiveWe aimed to determine whether 3D imaging reconstruction allows identifying molecular:clinical associations in myotonic dystrophy type 1 (DM1).MethodsWe obtained myoblasts from 6 patients with DM1 and 6 controls. We measured cytosine-thymine-guanine (CTG) expansion and detected RNA foci and muscleblind like 1 (MBNL1) through 3D reconstruction. We studied dystrophia myotonica protein kinase (DMPK) expression and splicing alterations of MBNL1, insulin receptor, and sarcoplasmic reticulum Ca(2+)-ATPase 1.ResultsThree-dimensional analysis showed that RNA foci (nuclear and/or cytoplasmic) were present in 45%–100% of DM1-derived myoblasts we studied (range: 0–6 foci per cell). RNA foci represented <0.6% of the total myoblast nuclear volume. CTG expansion size was associated with the number of RNA foci per myoblast (r = 0.876 [95% confidence interval 0.222–0.986]) as well as with the number of cytoplasmic RNA foci (r = 0.943 [0.559–0.994]). Although MBNL1 colocalized with RNA foci in all DM1 myoblast cell lines, colocalization only accounted for 1% of total MBNL1 expression, with the absence of DM1 alternative splicing patterns. The number of RNA foci was associated with DMPK expression (r = 0.967 [0.079–0.999]). On the other hand, the number of cytoplasmic RNA foci was correlated with the age at disease onset (r = −0.818 [−0.979 to 0.019]).ConclusionsCTG expansion size modulates RNA foci number in myoblasts derived from patients with DM1. MBNL1 sequestration plays only a minor role in the pathobiology of the disease in these cells. Higher number of cytoplasmic RNA foci is related to an early onset of the disease, a finding that should be corroborated in future studies.

DM1 Phenotype Variability and Triplet Repeat Instability: Challenges in the Development of New Therapies.

Myotonic dystrophy type 1 (DM1) is a complex neuromuscular disease caused by an unstable cytosine thymine guanine (CTG) repeat expansion in the DMPK gene. This disease is characterized by high clinical and genetic variability, leading to some difficulties in the diagnosis and prognosis of DM1. Better understanding the origin of this variability is important for developing new challenging therapies and, in particular, for progressing on the path of personalized treatments. Here, we reviewed CTG triplet repeat instability and its modifiers as an important source of phenotypic variability in patients with DM1.

Clinical and genetic characteristics of childhood-onset myotonic dystrophy.

Myotonic dystrophy type 1 (DM1) is caused by a CTG (cytosine-thymine-guanine) trinucleotide repeat expansion. Congenital DM (CDM) presents in the first month of life, whereas individuals with infantile and juvenile DM1 have later onset of symptoms. We performed a retrospective chart review of patients with childhood-onset DM1 seen at one of three locations in Dallas, Texas between 1990 and 2018. Symptoms, disease course, cognitive features, and family history were reviewed. Seventy-four patients were included; CDM was diagnosed in 52 patients. There was maternal inheritance in 74% of patients. CTG repeat number ranged from 143 to 2300. Neuropsychiatric and cognitive deficits were common. Over half of the patients had GI disturbances, and orthopedic complications were common. Myotonic dystrophy type 1 in children requires a multidisciplinary approach to management. Presenting symptoms vary, and repeat expansion size does not necessarily directly relate to severity of symptoms. A consensus for outcome measures is required.

Differences in the pattern of cognitive impairments between juvenile and adult onset myotonic dystrophy type 1

ObjectiveTo understand the different patterns of neuropsychological dysfunction observed between juvenile onset (jDM1) and adult onset (aDM1) myotonic dystrophy type 1. MethodWe enrolled 19 genetically confirmed DM1 patients, and neuropsychological tests—Wechsler Adult Intelligence Scale-Revised short form; Rey–Kim memory test; and Executive Intelligence Test for evaluating intelligence, memory, and executive function—were performed. Clinical parameters including cytosine-thymine-guanine (CTG) repeats, creatinine kinase level, pulmonary function test, six-minute walk test, motor scales, and cardiac function were evaluated. ResultsVerbal intelligence was significantly lower in the jDM1 than the aDM1 group (7.50 ± 1.64 vs. 11.00 ± 2.54, respectively; p = 0.009), while no difference was observed in performance intelligence. There was significant differences between the two groups (p = 0.022) with respect to memory function, as specifically revealed by the pattern of lower function in the verbal memory of the jDM1 group. However, the executive function test showed no intergroup differences. ConclusionVerbal memory impairment significantly deteriorated in the jDM1 group as compared to the aDM1 group, reflecting a more profound neurodevelopmental change in the juvenile type.

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

PurposeMyotonic 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.MethodsWe 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).ResultsWe 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.ConclusionClinical 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 characteristics of pregnancies complicated by congenital myotonic dystrophy

ObjectiveAlthough 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.MethodsWe 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.ResultsNone 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.ConclusionOur 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.

Genome Therapy of Myotonic Dystrophy Type 1 iPS Cells for Development of Autologous Stem Cell Therapy

Myotonic dystrophy type 1 (DM1) is caused by expanded Cytosine-Thymine-Guanine (CTG) repeats in the 3'-untranslated region (3' UTR) of the Dystrophia myotonica protein kinase (DMPK) gene, for which there is no effective therapy. The objective of this study is to develop genome therapy in human DM1 induced pluripotent stem (iPS) cells to eliminate mutant transcripts and reverse the phenotypes for developing autologous stem cell therapy. The general approach involves targeted insertion of polyA signals (PASs) upstream of DMPK CTG repeats, which will lead to premature termination of transcription and elimination of toxic mutant transcripts. Insertion of PASs was mediated by homologous recombination triggered by site-specific transcription activator-like effector nuclease (TALEN)-induced double-strand break. We found genome-treated DM1 iPS cells continue to maintain pluripotency. The insertion of PASs led to elimination of mutant transcripts and complete disappearance of nuclear RNA foci and reversal of aberrant splicing in linear-differentiated neural stem cells, cardiomyocytes, and teratoma tissues. In conclusion, genome therapy by insertion of PASs upstream of the expanded DMPK CTG repeats prevented the production of toxic mutant transcripts and reversal of phenotypes in DM1 iPS cells and their progeny. These genetically-treated iPS cells will have broad clinical application in developing autologous stem cell therapy for DM1.

Myotonic Dystrophy Type 1 with Syringomyelia in a Young Patient

Myotonic Dystrophy Type 1 with Syringomyelia in a Young Patient

Investigation of molecular diagnosis in Chinese patients with myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystem disease caused by abnormal expansion of cytosine-thymine-guanine (CTG) repeats in the myotonic dystrophy protein kinase gene. The clinical manifestations of DM1 are multisystemic and highly variable, and the unstable nature of CTG expansion causes wide genotypic and phenotypic presentations, which make molecular methods essential for the diagnosis. So far, very few studies about molecular diagnosis in Chinese patients with DM1 have been reported. Therefore, we carried out a study using two different methods in molecular diagnosis to verify the validity in detecting CTG expansion in Chinese patients showing DM signs. A total of 97 Chinese individuals were referred for molecular diagnosis of DM1 using conventional polymerase chain reaction (PCR) accompanied by Southern blotting and triplet primed PCR (TP-PCR). We evaluated the sensitivity and limitation of each method using percentage. By conventional PCR 65 samples showed only one fragment corresponding to the normal allele and 62 out of them were correctly diagnosed as DM1 by TP-PCR and three homologous non-DM1 samples were ruled out; Southern blotting analysis successfully made 13 out of 16 correct diagnoses with a more sensitivity using α-(32)P-labeled probes than dig-labeled probes. Molecular analysis is necessary for the diagnosis of DM1 and TP-PCR is a reliable, sensitive, and easily performed method in molecular diagnosis which is worthy to be popularized.

Association and Familial Segregation of CTG18.1 Trinucleotide Repeat Expansion ofTCF4Gene in Fuchs' Endothelial Corneal Dystrophy

We tested the association between two intronic polymorphisms (CTG18.1 and rs613872) in TCF4 and Fuchs' endothelial corneal dystrophy (FECD), and analyzed their segregation patterns in families. We recruited 120 unrelated Caucasian subjects with FECD and 100 controls. Available family members of probands were recruited. Genotyping of the single nucleotide polymorphism (SNP) rs613872 was performed using Sanger sequencing or real-time allelic discrimination assay. The trinucleotide repeat polymorphism, CTG18.1, was genotyped using a combination of short tandem repeat assay and triplet repeat primed PCR assay. The cytosine-thymine-guanine (CTG) repeat length of ≥40 was classified as an expanded CTG18.1 allele. Association of the two loci with FECD was evaluated. Segregation in 29 families was examined. The two polymorphisms are in linkage disequilibrium (r(2) = 0.65 in cases and 0.31 in controls). Significant associations were found between FECD and rs613872 (P = 3.1 × 10(-17)), expanded CTG18.1 allele (P = 6.5 × 10(-25)), and their haplotypes (P = 5.9 × 10(-19)). The odds ratio (OR) of each copy of the rs613872 G allele for FECD was estimated to be 9.5 (95% confidence interval [CI], 5.1-17.5). The OR of each copy of the CTG18.1 expanded allele was estimated to be 32.3 (95% CI, 13.4-77.6). The expanded CTG 18.1 allele cosegregated with the trait in 52% (15/29) of families with complete penetrance and 10% (3/29) with incomplete penetrance. We report, to our knowledge, the first independent replication of the expanded CTG 18.1 allele conferring significant risk for FECD (>30-fold increase). The expanded allele cosegregates with the trait with complete penetrance in a majority of families, but we also document cases of incomplete penetrance.

Modelling and inference reveal nonlinear length-dependent suppression of somatic instability for small disease associated alleles in myotonic dystrophy type 1 and Huntington disease

More than 20 human genetic diseases are associated with inheriting an unstable expanded DNA simple sequence tandem repeat, for example, CTG (cytosine-thymine-guanine) repeats in myotonic dystrophy type 1 (DM1) and CAG (cytosine-adenine-guanine) repeats in Huntington disease (HD). These sequences mutate by changing the number of repeats not just between generations, but also during the lifetime of affected individuals. Levels of somatic instability contribute to disease onset and progression but as changes are tissue-specific, age- and repeat length-dependent, interpretation of the level of somatic instability in an individual is confounded by these considerations. Mathematical models, fitted to CTG repeat length distributions derived from blood DNA, from a large cohort of DM1-affected or at risk individuals, have recently been used to quantify inherited repeat lengths and mutation rates. Taking into account age, the estimated mutation rates are lower than predicted among individuals with small alleles (inherited repeat lengths less than 100 CTGs), suggesting that these rates may be suppressed at the lower end of the disease-causing range. In this study, we propose that a length-specific effect operates within this range and tested this hypothesis using a model comparison approach. To calibrate the extended model, we used data derived from blood DNA from DM1 individuals and, for the first time, buccal DNA from HD individuals. In a novel application of this extended model, we identified individuals whose effective repeat length, with regards to somatic instability, is less than their actual repeat length. A plausible explanation for this distinction is that the expanded repeat tract is compromised by interruptions or other unusual features. We quantified effective length for a large cohort of DM1 individuals and showed that effective length better predicts age of onset than inherited repeat length, thus improving the genotype-phenotype correlation. Under the extended model, we removed some of the bias in mutation rates making them less length-dependent. Consequently, rates adjusted in this way will be better suited as quantitative traits to investigate cis- or trans-acting modifiers of somatic mosaicism, disease onset and progression.

The effect of rocuronium and sugammadex on neuromuscular blockade in a child with congenital myotonic dystrophy type 1

Myotonic dystrophy type 1 (MD1) is the commonest muscular dystrophy found in adults; however, it may present in the neonatal period with hypotonia, talipes, poor feeding, and respiratory failure. Inheritance is autosomal dominant with a defect in the DMPK gene found on the long arm of chromosome 19 with variable expansion of the cytosine-thymine-guanine (CTG) triplet repeat. A 14-month-old boy with congenital MD type 1 was scheduled for percutaneous endoscopic gastrostomy (PEG) insertion, orchidopexy, and division of tongue-tie. Following induction of anesthesia, acceleromyography was used to monitor neuromuscular function. This revealed a very rapid onset of profound neuromuscular block which lasted significantly longer than would be expected in a child without MD1. Sugammadex reversed the block rapidly. The anesthetic management of children with MD1 has been well described but not the acceleromyographic monitored use of rocuronium and its subsequent reversal with the new cyclodextrin sugammadex.

Genetics correlates with lung function and nocturnal ventilation in myotonic dystrophy

Dystrophia myotonica (DM) is the most frequent adult-onset muscular dystrophy. Type 1 is caused by the cytosine-thymine-guanine (CTG) repeat expansion in the DM protein kinase gene. Respiratory muscle weakness and altered central ventilatory control lead to hypercapnia and lung volume restriction. This study aims to review the respiratory involvement in DM patients and study its relation with genetics. Retrospective study of patients with DM referred for respiratory assessment was made. Noninvasive ventilation (NIV) was considered to daytime hypercapnia or symptoms of nocturnal hypoventilation. Forty-two consecutive patients (37.9 ± 13.6 years) were evaluated. Mean CTG length was 642.8 ± 439.2 repeats. In the first evaluation, mean forced vital capacity (FVC) was 74.4 ± 20.2 %, maximal expiratory pressure (MEP) 35 ± 16 %, maximal inspiratory pressure 52 ± 23 %, peak cough flow (PCF) 327.3 ± 97.7 L/min, arterial pressure of oxygen 79.7 ± 11.3 mmHg, arterial pressure of carbon dioxide 45.5 ± 6.2 mmHg, overnight minimal peripheral oxygen saturation (SpO2) 79.6 ± 11.6 %, and apnea-hypopnea index 13.9 ± 9.9. CTG length was found to be related with MEP (r = -0.67; p = 0.001) and SpO2 (r = -0.37; p = 0.039). NIV was started in 25 patients. Ventilated patients had lower FVC (2.19 to 3.21 L; p < 0.001) and PCF (285.3 to 388.5 L/min; p = 0.003) and more CTG repeats (826.6 to 388.5 repeats; p = 0.02). NIV compliance was poor in seven patients (28 %) and related with hypercapnia (r = 0.87; p = 0.002) and inspiratory positive airway pressure setting (r = 0.65; p = 0.009). Ventilation improved symptoms and nocturnal hypoventilation. Comparing the first and last evaluations, only PCF was significantly lower (275.0 to 310.8 L/min; p = 0.019). Ventilatory insufficiency is very common in patients with DM and CTG length may be useful to predict it. Prolonged NIV improves symptoms, nocturnal hypoventilation and maintains daily blood gases. Routine evaluation of PCF should not be forgotten and assisted coughing training provided.

Psychiatric and cognitive phenotype of childhood myotonic dystrophy type 1

To investigate the psychiatric and cognitive phenotype in young individuals with the childhood form of myotonic dystrophy type 1 (DM1). Twenty-eight individuals (15 females, 13 males) with childhood DM1 (mean age 17y, SD 4.6, range 7-24y) were assessed using standardized instruments and cognitive testing of general intelligence, visual attention, and visual-spatial construction abilities. Nineteen patients had repeated a school grade. The mean (SD) Full-scale IQ was 73.6 (17.5) and mean Verbal IQ was significantly higher than the mean Performance IQ: 80.2 (19.22) versus 72.95 (15.58), p=0.01. Fifteen patients had one or more diagnoses on the DSM-IV axis 1, including internalizing disorders (phobia, n=7; mood disorder, n=6; other anxiety disorders, n=5) and attention-deficit-hyperactivity disorder, inattentive subtype (n=8). Twelve out of 22 patients had alexithymia (inability to express feelings with words and to recognize and share emotional states). Cognitive testing found severe impairments in visual attention and visual-spatial construction abilities in four out of 18, and 14 out of 24 patients respectively. No diagnosis was correlated with the transmitting parent's sex or with cytosine-thymine-guanine (CTG) repeat numbers. Patients with severe visual-spatial construction disabilities had a significantly longer CTG expansion size than those with normal visual-spatial abilities (p=0.04). Children and adolescents with childhood DM1 have frequent diagnoses on DSM-IV axis 1, with internalizing disorders being the most common type of disorder. They also have borderline low intelligence and frequent impairments in attention and visual-spatial construction abilities.

Ocular motor function in relation to gross motor function in congenital and childhood myotonic dystrophy type 1

To assess ocular motor function in congenital and childhood myotonic dystrophy type 1 (DM1) and correlate the results with cytosine-thymine-guanine (CTG) repeat size, severity of the disease, myotonia and skeletal muscle function. A cross-sectional investigation into strabismus, versions/ductions, saccades, smooth pursuit movements and ptosis was performed on 49 individuals with a confirmed diagnosis of DM1, all diagnosed at <18 years of age and with >40 CTG expansion repeats. The results were correlated with myotonia as well as Hammersmith motor ability scale (HMA). In addition, the ocular results were compared to results from an age and- sex-matched control group. Ocular motor abnormalities were seen in 82%; the most frequent findings were altered conjugate eye movements and 'pseudoptosis' while blepharoptosis was rare. Strabismus was most common in the severe congenital subgroup, with a frequency 14 times higher than in the control group. Positive correlations were seen between CTG repeat size and affected eyelids, and between myotonia and affected eyelids; both these findings were most prominent in the mild congenital group. CTG repeat size was also correlated with version/duction defects, and most obviously in the childhood group. Low HMA scores were associated with high occurrence of strabismus and version/duction defects. Abnormalities of ocular motor function are frequently present. CTG repeat size correlates positively with altered versions/ductions and eyelid pathology. Gross motor dysfunction correlates with strabismus and defect versions/ductions, and eyelid pathology indicates involvement of myotonia.