This retrospective clinical study included four neonates diagnosed with congenital myotonic dystrophy (CDM) who were admitted to the neonatal intensive care unit (NICU) of the First Affiliated Hospital of Anhui Medical University between January 2023 and December 2024. All cases were genetically confirmed by DMPK gene testing. Since this study included only four neonates with genetically confirmed CDM, it was designed as a retrospective clinical case series using descriptive analysis rather than inferential statistics, which is appropriate for the small sample size and exploratory nature of the research.

Inclusion criteria were: (1) complete perinatal and genetic data available; (2) diagnosis confirmed by abnormal CTG repeat expansion in the DMPK gene; and (3) availability of detailed maternal and neonatal records. The study protocol was reviewed and approved by the institutional Ethics Committee (Approval No. Ethics-PJ 2023-14-25), and written informed consent for participation and publication was obtained from the parents of all participants.

Relevant clinical information was retrospectively collected from the hospital's electronic medical records. Data collection included: maternal history (age, gravidity, parity, amniotic fluid volume, fetal movements, medications during pregnancy); neonatal demographics (sex, gestational age, birth weight, mode of delivery, Apgar scores at 1, 5, and 10 min); perinatal manifestations (muscle tone, limb posture, respiratory effort, feeding ability); laboratory and imaging findings (cardiac enzymes, coagulation profile, EEG, ECG, echocardiogram, cranial ultrasound or MRI); and genetic testing results (DMPK CTG repeat number in the proband and the mother). Treatment measures, respiratory support, and short-term outcomes were also recorded.

The diagnosis of congenital myotonic dystrophy was based on the combination of clinical manifestations (severe neonatal hypotonia, respiratory insufficiency, feeding difficulties, and typical facial features) and genetic confirmation of abnormal CTG trinucleotide repeat expansion in the DMPK gene. For perinatal asphyxia, classification was based on Apgar scores: severe asphyxia (Apgar score ≤3 at 1 min); mild asphyxia (Apgar score 4–7 at 1 min); and no asphyxia (Apgar score ≥8). This grading allowed comparison of neonatal outcomes in relation to the severity of asphyxia.

Genetic testing for the DMPK gene was performed in all neonates and their mothers. Triplet-primed polymerase chain reaction (TP-PCR) followed by capillary electrophoresis was used to detect CTG repeat expansions. Results were reported in the format of “X/>Y”, indicating the number of repeats in the normal and expanded alleles, respectively (for example, “10/>150” means 10 repeats on the normal allele and >150 on the expanded allele). In clinical interpretation, <35 repeats were considered normal, 35–49 as a premutation, and ≥50 as pathogenic.

A total of four neonates with genetically confirmed CDM were included in the study. Cases 1 and 2 were extremely preterm infants with gestational ages of 31 + 2 and 28 + 6 weeks, respectively, and both had extremely low birth weights. Case 3 was a late preterm infant at 36 + 1 weeks of gestation, while Case 4 was born at full term.

All three preterm infants were born to mothers with a history of polyhydramnios; two were delivered via cesarean section, and one via spontaneous vaginal delivery. Among them, two mothers had adverse obstetric histories. The full-term infant's mother had normal amniotic fluid volume and underwent vaginal delivery assisted by forceps, with no adverse obstetric history. Decreased fetal movement was reported during pregnancy in all four cases (See Table 1 for a summary of maternal and neonatal characteristics of each case).

All three preterm infants experienced birth asphyxia, with two classified as severe. They presented with flaccid limbs, wrist drop, and marked hypotonia, accompanied by respiratory failure and significantly elevated myocardial enzyme levels. Two cases also had coagulation abnormalities, and two presented with congenital cardiac anomalies, including atrial septal defect and patent ductus arteriosus.

The full-term infant did not suffer from birth asphyxia but developed progressive respiratory distress postnatally. Marked hypotonia was noted, along with a tent-shaped upper lip (“inverted V” appearance), persistent frog-leg positioning of the hips (hips abducted with knees flexed), and severe feeding and swallowing difficulties that necessitated respiratory support.

All three preterm infants underwent neonatal resuscitation due to asphyxia, with one case requiring intravenous administration of epinephrine. All four neonates required prolonged mechanical ventilation with difficult weaning. Two of the preterm infants developed ventilator-associated pneumonia and were treated with cefoperazone-sulbactam for infection control.

Genetic testing confirmed maternally inherited abnormal CTG trinucleotide repeat expansions in the DMPK gene in all four neonates, consistent with congenital myotonic dystrophy type 1 (CDM1).Specifically, Case 1 carried a repeat length of >150 on the expanded allele and 10 repeats on the normal allele, while the mother showed the same expansion pattern. Case 2 exhibited >50 repeats on the expanded allele and 4 repeats on the normal allele; Case 3 had >50 and 5 repeats, respectively;and Case 4 demonstrated >150 repeats on the expanded allele and 11 on the normal allele, with the mother presenting 13/>150 repeats. These data confirm maternal transmission of the pathogenic DMPK expansion in all cases.

In general, CTG repeat lengths in congenital DM1 are often very large, frequently exceeding 1,000 repeats; however, in this study, several expanded alleles were reported as “>50”, which may reflect limitations of the detection range inherent to the testing platform rather than smaller true expansions.

Cases 1 and 2 died within hours after withdrawal of treatment during hospitalization. Case 3 was transferred to another hospital, where treatment was also discontinued and the patient subsequently died. Case 4 responded well to supportive care, was successfully weaned off mechanical ventilation and oxygen, achieved full oral feeding, and was discharged. At the time of writing, the infant had survived for over five months but exhibited delayed developmental milestones.

The principal observations from our series are (1) frequent prenatal polyhydramnios and reduced fetal movements in affected pregnancies, (2) severe hypotonia with respiratory insufficiency as the dominant early neonatal problem, and (3) markedly worse short-term outcomes in preterm infants and those requiring resuscitation at birth. These findings are concordant with prior reports that identify polyhydramnios as a common prenatal clue to CDM and that emphasize respiratory failure as the major driver of neonatal mortality (6). In particular, prenatal polyhydramnios has been highlighted as a frequent feature in CDM cohorts, supporting the importance of sonographic vigilance when polyhydramnios co-occurs with decreased fetal movements (7).

Multiple studies have suggested that gestational age at delivery substantially modifies early outcomes in CDM, with preterm infants experiencing far greater respiratory vulnerability (8, 9). Our observation—that the three preterm infants died while the sole term infant survived with multidisciplinary support—echoes these reports and reinforces the clinical message that prematurity is an important negative prognostic factor in CDM. Moreover, our data suggest that the need for resuscitation at birth is associated with particularly poor short-term outcomes; while literature directly quantifying this association is limited, several clinical series and reviews note worse neonatal trajectories when significant perinatal compromise coexists with the muscular and central respiratory impairment of CDM (10). These findings support heightened peripartum preparedness (advanced respiratory support and early rehabilitation) for at-risk pregnancies.

Consistent with previous reports, our cases exhibit the characteristic neonatal phenotype—global hypotonia, feeding difficulty, and variable musculoskeletal findings (contractures, possible hip dysplasia, cryptorchidism) (11, 12). Notably, some features (e.g., ventriculomegaly, late-onset ophthalmic changes) may not be apparent in the immediate neonatal period and can emerge later, underscoring the need for longitudinal follow-up. These observations align with natural-history descriptions indicating an evolving multisystem phenotype beyond the neonatal timeline (13).

The relationship between CTG repeat size and clinical severity is well established in DM1, with congenital cases frequently carrying very large expansions (classically in the thousands), but measurement practices and reporting conventions vary between laboratories (14, 15). Some diagnostic platforms report upper-range values as “>50” or “>150” due to technical sizing limits; such platform thresholds should not be interpreted as implying that an expansion is only modest (16, 17). Therefore, while our genetic results (reported as normal-allele/expanded-allele formats) confirm maternal transmission and support the diagnosis, we explicitly acknowledge that reported “>50” values may reflect assay ceilings rather than true biological upper bounds. When precise sizing is required for genotype–phenotype analyses, Southern blot or long-read approaches (or validated TP-PCR sizing kits) may be necessary.

Because many mothers are asymptomatic or undiagnosed carriers prior to pregnancy, CDM may escape prenatal detection unless sonographic and clinical vigilance is applied (18). Our findings support current recommendations that polyhydramnios with decreased fetal movements, especially when combined with other sonographic clues, should prompt genetic counseling and consideration of targeted DMPK testing. Early recognition enables multidisciplinary planning (obstetrics, neonatology, genetics) to optimize delivery timing, airway and respiratory preparedness, and immediate neonatal support.

This single-center retrospective series is small and descriptive, so causal inference and statistical generalization are not possible. Follow-up is limited for longer-term neurodevelopmental outcomes. Additionally, non-uniformity in CTG sizing methods limits genotype–phenotype interpretation. To advance the field, prospective multicenter registries with standardized repeat-sizing methods and longitudinal neurodevelopmental assessments are needed to refine risk stratification and to evaluate targeted perinatal interventions.

In summary, our case series corroborates key clinical hallmarks of CDM reported in the literature—notably prenatal polyhydramnios, neonatal hypotonia with respiratory compromise, and marked vulnerability in preterm infants—and highlights the prognostic relevance of gestational maturity and perinatal stability. By explicitly linking our observations with prior studies and clarifying methodological considerations, we aim to improve clinicians' ability to recognize at-risk pregnancies and to prepare appropriate perinatal care pathways.