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

Abstract

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.

Muscle dystrophies in children

“…In the current study CPK range in the LGMD group was (255-31219 IU/ L) with a mean of 10390. 2019), similar to our results, gender distribution was found to be 12 males (70.6 %) and 5 females (29.4 %) [18]. In contrast to that, according to a study done by Solbakken et al (2019), there were no significant differences in age or gender between the patients and the control group [19].…”

Impact of prematurity and the CTG repeat length on outcomes in congenital myotonic dystrophy

“…We revealed that OR decreased by 27% with 1 week increase in gestational age, whereas OR increased by 31.27 with 1 unit increase in log 2 CTG repeat length, in other words, OR increased by 31.27 whenever the number of CTG repeat length doubled. The current clinical classi cation of DM1 is based on age at onset and CTG length [7,12,13,34,35]. On the other hand, several reports have shown no evidence of an effect of CTG repeat length on clinical severity [8,11,36].…”

“…Another reason for this nding is that the term CDM newborns had fewer CTG repeats (median: 1300) than preterm ones (median of 1900). Several studies have indicated the CTG repeat correlated with the disease phenotype [8,34,35]. Thus, having few CTG repeats with term CDM newborns induces a favorable outcome.…”

Impact of prematurity and the CTG repeat length on outcomes in congenital myotonic dystrophy

“…We revealed that OR decreased by 27% with 1 week increase in gestational age, whereas OR increased by 31.27 with 1 unit increase in log 2 CTG repeat length, in other words, OR increased by 31.27 whenever the number of CTG repeat length doubled. The current clinical classification of DM1 is based on age at onset and CTG length [ 7 , 12 , 13 , 34 , 35 ]. On the other hand, several reports have shown no evidence of an effect of CTG repeat length on clinical severity [ 8 , 11 , 36 ].…”

“…Another reason for this finding is that the term CDM newborns had fewer CTG repeats (median: 1300) than preterm ones (median of 1900). Several studies have indicated the CTG repeat correlated with the disease phenotype [ 8 , 34 , 35 ]. Thus, having few CTG repeats with term CDM newborns induces a favorable outcome.…”