Kim, Hyeong Jung
(Department of Pediatrics, Yonsei University College of Medicine)
,
Na, Ji-Hoon
(Department of Pediatrics, Yonsei University College of Medicine)
,
Lee, Young-Mock
(Department of Pediatrics, Yonsei University College of Medicine)
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 ...
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. ${\geq}1,000$). 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.
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. ${\geq}1,000$). 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.
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문제 정의
Thus, our aim was to determine whether a correlation between severity of clinical phenotype and length of the CTG repeat region could be established for better classification of the disease in affected individuals.
We identified 30 patients with DM1, who were followed up in 2 centers of our hospital (Gangnam Severance Hospital and Severance Children’s Hospital), through a retrospective study (Fig. 1).
대상 데이터
1). All participants were diagnosed with DM1 by genetic testing of DMPK from November 2005 to June 2017. Thirteen patients were excluded from the study due to poor clinical data.
성능/효과
3% of all patients showed increased creatinine kinase (CK), there was no significant difference between the 2 subgroups (Table 3). In addition, abnormal findings in brain MRI were more common in the congenital-onset subgroup compared to that in the late-onset subgroup (85.7% vs. 50.0%, respectively), though not statistically significant. In the last out-patient follow-up visit, dependence on ventilator was higher in the congenital-onset subgroup compared to that in the late-onset subgroup (50.
However, there have been few studies that subgrouped patients according to age of onset to compare prominent clinical features between groups. One study divided patients into 5 clinical categories (congenital, infantile, juvenile, adult-onset, and late-onset) and found that muscle weakness typically arises earlier in the congenital group, whereas myotonia was the earliest prominent symptom in patients from the infantile group. Early cardiac defects were prominent in juvenile group, whereas secondary symptoms, such as cataract and endocrine disorders, were prominent in the adult-onset group.
5% in the small CTG subgroup. The proportion of cases requiring NICU admission and need for respiratory support was both 75.0% in the large CTG subgroup compared to 80.0% and 60.0%, respectively, in the small CTG subgroup. Poor feeding in neonate was found to be the only symptom that was significantly increased in patients in the large CTG subgroup, compared to that found in the small CTG subgroup (88.
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