Developmental Malformations
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Myotonic muscular dystrophy (neonatal) …
- Updated 05.30.2024
- Released 04.02.2002
- Expires For CME 05.30.2027
Myotonic muscular dystrophy (neonatal)
Introduction
Overview
Congenital myotonic dystrophy is a multisystem disorder characterized by hypotonia, muscle weakness, respiratory insufficiency, feeding issues, and joint contractures in the neonatal period. Most cases are maternally transmitted due to an abnormal trinucleotide (CTG) repeat expansion of the DMPK gene. In this article, the author reviews the clinical features of children with congenital myotonic dystrophy. Extramuscular manifestations, including cardiac arrhythmias, cognitive impairment, gastrointestional disorders, and maladaptive behaviors, are important challenges for these children. Affected individuals who survive beyond the infancy period generally experience an improvement in their motor function during childhood. Natural history studies and early results from clinical trials offer hope of new disease-modifying therapies for congenital myotonic dystrophy.
Key points
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• Myotonic dystrophy type 1 is an autosomal dominant disorder due to abnormal expansion of trinucleotide repeats in the DMPK gene on chromosome 19q13.3. | |
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• The severe neonatal form of myotonic dystrophy type 1 is usually associated with 1000 or more CTG repeats, with the mother being the affected parent in the majority of cases. | |
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• Infants with the severe neonatal form of myotonic dystrophy type 1 present with hypotonia, generalized weakness, respiratory insufficiency, and feeding difficulties at birth. | |
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• Other potential long-term complications include developmental delay, learning disabilities, behavioral problems, and intellectual disability. | |
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• A multidisciplinary team approach is needed to address the supportive needs of affected children and their families. |
Historical note and terminology
In 1901 a rare, severe neonatal form of the already recognized disease of myotonic muscular dystrophy was first described by Gardiner (30). The clinical presentation was better defined in the 1960s and 1970s by several authors and was distinguished from the more common, slowly progressive disease of the older child and adult, though occurring in the same families (86; 20; 68; 90; 07; 22; 09; 33; 79; 74). Harper pointed out that in 94% of affected neonates of both sexes, the mother was the transmitting parent despite autosomal dominant inheritance that theoretically should not be gender-specific. Additional genetic studies in the early 1990s clarified the reason as a large number of trinucleotide repeats in the defective gene of type 1 myotonic dystrophy.
Clinical manifestations
Presentation and course
Affected infants have clinical problems before birth and are overtly symptomatic after delivery. Polyhydramnios is a common complication because of inadequate fetal swallowing of amniotic fluid. The most frequent clinical manifestations at birth are congenital contractures ranging from simple equinovarus deformities of the feet to arthrogryposis multiplex congenita involving the lower more than the upper limbs, generalized hypotonia, facial diplegia with characteristic inverted V-shaped upper lip, temporalis wasting, and pharyngeal weakness.
The characteristic facies and shape of the mouth may be the first clues to the diagnosis, but this is not pathognomonic and is shared with some congenital myopathies. The palate is often high and may even be cleft.
Dysphagia is common, and infants usually require gavage and eventually may require gastrostomy. Even infants who do not have frank dysphagia may feed slowly and poorly because of the facial weakness that results in weak sucking and drooling.
Respiratory insufficiency occurs in a significant proportion of neonates with congenital myotonic dystrophy, and these infants may require supplementary oxygen, positive airway pressure ventilation, or, in some cases, tracheostomy and chronic ventilatory support (09; 74). A hemidiaphragm may be demonstrated to be nonfunctional (74).
Electrocardiographic abnormalities are found in a minority and are usually conduction defects rather than cardiomyopathy. This cardiac abnormality is usually silent, but arrhythmias and transient complete atrioventricular block during the neonatal period are possible (43).
The testes of male infants often are undescended.
Congenital cataracts are infrequent and often require a slit-lamp examination to be detected early.
A serious complication of neonatal myotonic dystrophy is poor peristalsis due to smooth muscle involvement (74). The abdomen becomes distended from air in the stomach and intestines and may push up against the diaphragm, further compromising respiration. Obstipation and inability to pass stool, or even the meconium plug initially, is a difficult complication.
Poor muscle function of the gallbladder may also produce cholelithiasis or cholestasis (77).
Endocrine abnormalities may involve the thyroid and adrenal medulla for cortisol production as well as regulation of blood sugar because of insulin resistance; vigilance for hypoglycemia is needed.
Seizures are not a feature of neonatal myotonic dystrophy unless the infant has hypoxic-ischemic encephalopathy. Intrapartum asphyxia is a serious problem in infants delivered prematurely, and the risk of germinal matrix and intraventricular hemorrhage is greater than in preterm infants of comparable gestational age that do not have myotonic dystrophy (59). The MRI in congenital myotonic dystrophy often shows ventriculomegaly and hyperintensity of white matter posterior and superior to the trigone region, with no correlation to age or trinucleotide repeat size (46; 62).
Prognosis and complications
Prognosis is guarded for infants who have respiratory insufficiency and dysphagia, and many die early. Affected infants requiring ventilation support for more than 30 days had a 25% risk of mortality during the first year (14). Survivors generally experience an improvement in muscle strength and motor function during first decade of life (69), reaching a plateau during adolescence, and then decline after the second decade (45). Dysarthria is a frequent complication among children with congenital myotonic dystrophy due to impaired orofacial functioning (76; 08). These children may also have other chronic health issues related to gastrointestinal dysmotility, sphincter dysfunction, myotonia, cardiac arrhythmias, respiratory insufficiency, skeletal deformities, and cataracts (47). Difficulties with communication, fatigue, process and motor skills are frequent symptoms that negatively impact their activities of daily living and health-related quality of life (40; 25). Learning disabilities and cognitive impairment are common among children with congenital myotonic dystrophy (17; 78; 64). These individuals may display maladaptive behaviors that further restrict their social participation long term (28). In a longitudinal study, the gap in cognitive and adaptive functioning among children with congenital myotonic dystrophy type 1 widened over time compared to age-matched healthy controls (49). Furthermore, children and adolescents with myotonic dystrophy type 1 are at increased risk for neuropsychiatric comorbidities such as autistic spectrum conditions, anxiety, and attention deficit disorders (23; 24; 21; 47). In a study using United States insurance claims data from 2012 to 2019, the mean costs of healthcare resource utilization and all-cause healthcare expenses were found to be highest ($66,496 vs. $2828 USD) for patients with congenital myotonic dystrophy during the first 12-month follow up; their mean costs remained markedly elevated (above $17,944) across all subsequent period (up to 47-month) when compared to age matched controls due to their significant comorbidities (37).
Clinical vignette
A 1-day-old infant girl was referred for neurologic assessment because of multiple joint contractures, respiratory distress, and feeding difficulties. The pregnancy was by in vitro fertilization due to previous maternal miscarriages, and reduced fetal movement was noted antenatally. Cesarean section was performed at 36 weeks because of breech presentation. Her birth weight was 1.81 kg, and Apgar scores were 4 at 1 minute and 7 at 5 minutes. Mild dysmorphic features were noted, including down-sloping palpebral fissures, low-set ears, elevation of the palate, and short neck. She had bilateral talipes equinovarus feet, dislocated hips, and adducted thumbs. Aside from a grade 3/6 pansystolic ejection murmur, the remaining general exam was normal. Her neurologic exam revealed truncal hypotonia, reduced muscle bulk, diminished deep tendon reflexes, and diffuse muscle weakness. Her cranial nerves showed reduced facial expression and diminished gag response, with no tongue fasciculations or cataracts. She required supplemental oxygen during the first week and was gavage-fed until 3 weeks of age.
Exam of the mother was positive for distal hand weakness and grip myotonia, which had been noted since adolescence. She was otherwise in good health. The maternal grandfather had surgery for cataracts in his 50s and developed type II diabetes.
Subsequent investigations in this infant revealed mildly elevated creatine kinase of 461 U/L. Her serum glucose and thyroid functions were normal, as was her initial chest and abdominal x-ray. EKG showed normal sinus rhythm with left axis deviation and right ventricular hypertrophy. A small atrial and ventricular septal defect was noted on echocardiogram. Karyotype and newborn metabolic screen were normal. Molecular genetic testing showed 700 CTG trinucleotide repeats of the DMPK gene in the infant and 200 repeats in the mother.
Biological basis
Etiology and pathogenesis
Myotonic dystrophy type 1 is a multisystem autosomal dominant disorder due to abnormal expansion of CTG trinucleotide repeats in the 3’-untranslated region of the dystrophia myotonica protein kinase (DMPK) gene on chromosome 19q13.3 (10; 27; 52; 80). The amount of abnormal expansion generally correlates with the severity of the weakness and other clinical manifestations (45; 93). The number of CTG repeats in normal alleles is five to 37. In the more common adult and late-onset forms of myotonic dystrophy, more than 50 to 350 repeats are detected. Based on the French myotonic dystrophy patient registry, De Antonio and colleagues confirmed that earlier age at onset of disease (including the congenital, infantile, and juvenile forms) was associated with longer repeat length and more clinical severity, although substantial variability was noted among affected individuals (16). Both repeat length and prematurity were significantly associated with disease severity (72). In the severe, neonatal form of myotonic dystrophy type 1, 1000 or more repeats usually are demonstrated (70).
The CTG repeat allele on 19q13.3 is relatively stable in somatic tissues but highly unstable in the germline and extremely biased toward further expansion, which is consistent with the high level of anticipation observed in families (58). The mother is the affected parent in most cases because the gene is less stable in the maternal DNA of the ovum, and excessive repeats are, thus, more readily produced from the maternal DNA (70). Anticipation occurs more frequently in maternal (85%) than paternal (37%) transmissions (04). Paternal transmission has also been reported in rare cases of congenital myotonic dystrophy (81; 94; 18; 47). Barbé and colleagues proposed that CpG hypermethylation of an insulator protein CTCF binding (CTCF1) site flanking the CTG repeats in the DMPK gene may account for the maternal bias for congenital myotonic dystrophy transmission (06). Furthermore, the degree of CTCF1 hypermethylation is mutant allele length-dependent and may serve as a biomarker for congenital myotonic dystrophy (48; 57).
The genetic and molecular bases of the myotonic dystrophies are summarized in several reviews (55; 56; 02). In myotonic dystrophy type 1, abnormal intranuclear accumulations of ribonucleic acid (RNA) inclusions alter the activities of various RNA processing factors, including muscleblind-like (MBLN) and CUG-binding proteins (CUGBP), leading to misregulation of developmentally programmed alternative splicing (66; 50). Failure to express mature splicing transitions in targeted mRNAs and nuclear sequestration of muscleblind-like proteins impairs myogenic differentiation and leads to other cellular deregulation in various tissues; the degree of alternative splicing and polyadenylation abnormalities is significantly more extensive and occurs prenatally in congenital myotonic dystrophy type 1 (82; 32). Accumulation of mutant pre-mRNA and aberrant alternative splicing of a number of genes in the cortical neurons, including the microtubule-associated tau protein, the amyloid precursor protein, the SLITRK family of proteins, and the N-methyl-D-aspartate receptor 1, contributes to central nervous system disease in myotonic dystrophy type 1 (12; 31; 61). Other factors, including abnormal repeats-associated translation, activation of protein kinase C-dependent signaling pathway, aberrant polyadenylation, and microRNA deregulation, may also contribute to the complex pathogenic mechanisms (15; 17; 32).
The cause of striated muscle weakness in the neonatal period and early infancy is muscular immaturity rather than necrosis or degeneration. The muscle biopsy in neonatal myotonic dystrophy shows variable degrees of immaturity, with myoblasts, myotubes, undifferentiated myofibers, and mature myofibers all mixed randomly within the same fascicles; ultrastructural evidence of maturational delay corroborates the histological and histochemical findings (42; 26; 75).
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Severe neonatal myotonic dystrophy (quadriceps femoris muscle biopsy) (1)In transverse section, myofibers are smaller than expected, with an average diameter of 5 to 12.5µm (normal mean 15µm). About 20% of fibers have central nuclei or clear central spaces if the section is between nuclei, but no myofi...
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Severe neonatal myotonic dystrophy (quadriceps femoris muscle biopsy) (2)Longitudinal section shows the centronuclear fibers have large, vesicular nuclei in a row, but they are not closely spaced, and clear spaces are seen between nuclei. These spaces contain mitochondria, as in fetal myotubes. X250. (...
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Severe neonatal myotonic dystrophy (quadriceps femoris muscle biopsy) (3)Transverse frozen section stained with NADH-TR shows strong mitochondrial oxidative enzymatic activity in the centers of many myofibers, corresponding to the clear spaces seen in some myofibers with hematoxylin and eosin stain. X2...
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Severe neonatal myotonic dystrophy (quadriceps femoris muscle biopsy) (4)Electron microscopy confirms that some small fibers have central nuclei and others have concentrations of normal mitochondria in the central core of the fiber. Myofibrils are sparse but well formed. Lipid droplets are abundant. (R...
Persistent fetal expression of vimentin and desmin intermediate filaments also is demonstrated (73). Correlation between the number of trinucleotide repeats and the severity of maturational delay in muscle is poor, however (80). Another pattern of the muscle biopsy sometimes found in congenital myotonic dystrophy is congenital muscle fiber-type disproportion, either fully or partially developed, as uniform smallness and more than 80% predominance of type I myofibers (03; 84).
The muscle in neonatal myotonic dystrophy, unlike that of X-linked myotubular myopathy, is a true maturational arrest; the appearance of the biopsies in these two diseases is different and can be distinguished histologically. The absence of degenerating and regenerating myofibers and of connective tissue proliferation distinguishes neonatal myotonic dystrophy from congenital muscular dystrophy and the other form of muscular dystrophies.
Smooth muscle also is extensively involved in myotonic dystrophy and causes problems with gastrointestinal motility in the neonate and abnormal uterine contractures during labor in the pregnant mother (74).
Epidemiology
The reported incidence of congenital myotonic dystrophy ranges from 1 in 3500 to 100,000 live births (91; 13). All ethnic and racial groups are affected.
Prevention
Genetic counselling should be offered to individuals with a family history of myotonic dystrophy, and especially to those with confirmed DMPK mutation (41). Prenatal diagnosis is available from chorionic villus samples and cultured amniocytes, from which DNA analysis can be performed during the first half of gestation at 8 to 20 weeks. Fetal cord blood may be obtained in older fetuses and genetic studies performed on leukocytes. The analysis of DNA from these samples shows accuracy in CTG repeat size, and when combined with DNA methylation studies can help predict severe neonatal disease (70; 89). Trinucleotide repeats contraction is a pitfall to be aware of in the interpretation of genetic testing for prenatal diagnosis (01; 54). The frequency of contractions may be higher in DM1 families with variant (non-CTG) expansion repeats; long-read sequencing with assessments of the expansion size, the degree of somatic instability, as well as the pattern of variant repeats and DNA methylation may provide a more comprehensive understanding of disease severity in patients with myotonic dystrophy type 1 (65).
Differential diagnosis
Confusing conditions
The neonatal form of myotonic dystrophy should be differentiated from congenital muscular dystrophy, congenital myasthenia gravis, spinal muscular atrophy, mitochondrial cytopathy, severe congenital myopathies, amyoplasia, and other causes of arthrogryposis multiplex congenita.
Diagnostic workup
Neurologic examination of the parents, particularly of the mother, is essential. The single most important confirmatory diagnostic test is the molecular genetic marker in the blood for myotonic dystrophy type 1, which will also provide the number of trinucleotide repeats (93).
EMG is not helpful because myotonia is not yet developed at birth, and the findings are nonspecific. Muscle biopsy is now rarely indicated.
Roentgenograms of the chest and abdomen are used to help determine the status of diaphragmatic and gastrointestinal functions. Thin ribs are frequently demonstrated, as in other severe neuromuscular diseases beginning in fetal life. Ultrasound or fluoroscopy may be needed to further define diaphragmatic hemiparesis. A swallow study may be indicated for infants with feeding difficulties; close monitoring is required to detect early respiratory insufficiency. An electrocardiogram (EKG) should also be performed for all infants with myotonic dystrophy, even if asymptomatic; echocardiography and Holter monitoring may be required in subsequent follow up evaluations (88; 11). Brain MRI often reveals white matter disease, enlarged ventricles, cortical atrophy, and other nonspecific brain abnormalities (19; 31; 62; 17).
The eyes should be examined with a slit-lamp for congenital cataracts; standard direct ophthalmoscopy is not adequate. Endocrine evaluations, including serum cortisol, thyroid function, HgA1C, blood glucose, and lipid profile, should be performed periodically. Serum creatine kinase is nondiagnostic and may be normal.
Management
In the neonatal period, the most immediate needs are for respiratory and feeding support. The diagnosis must be confirmed. Attention to cardiac status and GI motility are important. Ventriculomegaly is common, but most cases will not require shunting (60). Arthrogryposis may require surgical correction of the most severe contractures, and physiotherapy should be started early. Early speech therapy referral is indicated to help with communication challenges (40; 76). Gastrointestinal and urological symptoms are common and often require treatment (39; 51). A multidisciplinary approach including psychosocial therapy is necessary to optimize the health outcomes of these children and prepare them for transition to adult services (29; 36; 05; 35; 39).
Emerging treatments including gene therapy are being evaluated for adults with myotonic dystrophy type 1 (44; 31; 67; 83; 53; 34). AMO-02, an inhibitor of an intracellular regulatory kinase GSK3B, was reported to have a favorable clinical profile in a clinical trial involving adolescents and adults with congenital and childhood-onset myotonic dystrophy type 1; further trial is on-going (38). Future therapies will hopefully ameliorate both the muscular and extramuscular manifestations of this disease (63).
Special considerations
Pregnancy
A high rate of fetal loss occurs due to spontaneous abortion, and premature delivery is frequent. In fetuses carried to term, fetal movements are reported by mothers to be less than in her other pregnancies with nonaffected infants. Maternal complications of abnormal labor due to poor uterine contractions, placenta previa, and retained placenta are several times more frequent in mothers with myotonic dystrophy than in the normal population (74; 92). Mothers with a known or suspected diagnosis of myotonic dystrophy type 1 should receive prenatal care by a high-risk obstetrician familiar with these potential complications. As well, a pediatrician or neonatologist should be present at delivery to provide necessary supportive care (39).
Anesthesia
There are no specific contraindications, but as with any congenital myopathy, the risk is high for apnea and respiratory failure after the anesthetic. Careful perioperative planning is required to minimize complications (87; 71; 85).
Media
References
- 01
- Amiel J, Raclin V, Jouannic JM, et al. Trinucleotide repeat contraction: a pitfall in prenatal diagnosis of myotonic dystrophy. J Med Genet 2001;38:850-2. PMID 11768387
- 02
- André LM, Ausems CRM, Wansink DG, Wieringa B. Abnormalities in skeletal muscle myogenesis, growth, and regeneration in myotonic dystrophy. Front Neurol 2018;9:368. PMID 29892259
- 03
- Argov Z, Gardner-Medwin D, Johnson MA, Mastaglia FL. Congenital myotonic dystrophy: fiber type abnormalities in two cases. Arch Neurol 1980;37:693-6. PMID 7436809
- 04
- Ashizawa T, Anvret M, Baiget M. Characteristics of intergenerational contractions of the CTG repeat in myotonic dystrophy. Am J Hum Genet 1994;54:414-23. PMID 8116611
- 05
- Baldanzi S, Ricci G, Simoncini C, Cosci O Di Coscio M, Siciliano G. Hard ways towards adulthood: the transition phase in young people with myotonic dystrophy. Acta Myol 2016;35(3):145-9. PMID 28484315
- 06
- Barbe L, Lanni S, López-Castel A, et al. CpG methylation, a parent-of-origin effect for maternal-biased transmission of congenital myotonic dystrophy. Am J Hum Genet 2017;100(3):488-505. PMID 28257691
- 07
- Bell DB, Smith DW. Myotonic dystrophy in the neonate. J Pediatr 1972;81:83-6. PMID 5034872
- 08
- Berggren KN, Hung M, Dixon MM, et al. Orofacial strength, dysarthria, and dysphagia in congenital myotonic dystrophy. Muscle Nerve 2018;58(3):413-7. PMID 29901230
- 09
- Bossen EH, Shelbourne JD, Verkauf BS. Respiratory muscle involvement in infantile myotonic dystrophy. Arch Pathol 1974;97:250-2. PMID 4814710
- 10
- Brook JD, McCurrach ME, Harley HG, et al. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3’ end of a transcript encoding a protein kinase family member. Cell 1992;68:799-808. PMID 1310900
- 11
- Brunet Garcia L, Hajra A, Field E, et al. Cardiac manifestations of myotonic dystrophy in a pediatric cohort. Front Pediatr 2022;10:910660. PMID 35757141
- 12
- Bugiardini E, Meola G, DM-CNS Group. Consensus on cerebral involvement in myotonic dystrophy: Workshop report: May 24-27, 2013, Ferrere (AT), Italy. Neuromuscul Disord 2014;2(5)4:445-52. PMID 24613228
- 13
- Campbell C, Levin S, Siu VM, Venance S, Jacob P. Congenital myotonic dystrophy: Canadian population-based surveillance study. J Pediatr 2013;163(1):120-5.e1-3. PMID 23415617
- 14
- Campbell C, Sherlock R, Jacob P, Blayney M. Congenital myotonic dystrophy: assisted ventilation duration and outcome. Pediatrics 2004;113:811-6. PMID 15060232
- 15
- Chau A, Kalsotra A. Developmental insights into the pathology of and therapeutic strategies for DM1: Back to the basics. Dev Dyn 2015;244:377-90. PMID 25504326
- 16
- De Antonio M, Dogan C, Hamroun D, et al. Unravelling the myotonic dystrophy type 1 clinical spectrum: a systematic registry-based study with implications for disease classification. Rev Neurol (Paris) 2016;172(10):572-80. PMID 27665240
- 17
- De Serres-Berard T, Pierre M, Chahine M, Puymirat J. Deciphering the mechanisms underlying brain alterations and cognitive impairment in congenital myotonic dystrophy. Neurobiol Dis 2021;160:105532. PMID 34655747
- 18
- Di Costanzo A, de Cristofaro M, Di Iorio G, Daniele A, Bonavita S, Tedeschi G. Paternally inherited case of congenital DM1: brain MRI and review of literature. Brain Dev 2009;31(1):79-82. PMID 18541397
- 19
- Di Costanzo A, Santoro L, de Cristofaro M, Manganelli F, Di Salle F, Tedeschi G. Familial aggregation of white matter lesions in myotonic dystrophy type 1. Neuromuscul Disord 2008;18:299-305. PMID 18337099
- 20
- Dodge PR, Gamstorp I, Byers RK, Russell P. Myotonic dystrophy in infancy and childhood. Pediatrics 1965;35:3-19. PMID 14223223
- 21
- Douniol M, Jacquette A, Guilé JM, et al. Psychiatric and cognitive phenotype in children and adolescents with myotonic dystrophy. Eur Child Adolesc Psychiatry 2009;18(12):705-15. PMID 19543792
- 22
- Dyken PR, Harper PS. Congenital dystrophia myotonica. Neurology 1973;24:465-73. PMID 4735462
- 23
- Echenne B, Rideau A, Roubertie A, Sebire G, Rivier F, Lemieux B. Myotonic dystrophy type I in childhood Long-term evolution in patients surviving the neonatal period. Eur J Paediatri Neurol 2008;12:210-23. PMID 17892958
- 24
- Ekstrom AB, Hakenas-Plate L, Samuelsson L, Tulinius M, Wentz E. Autism spectrum conditions in myotonic dystrophy type 1: a study on 57 individuals with congenital and childhood forms. Am J Med Genet B Neuropsychiatr Genet 2008;147B:918-26. PMID 18228241
- 25
- Eriksson BM, Ekström AB, Peny-Dahlstrand M. Daily activity performance in congenital and childhood forms of myotonic dystrophy type 1: a population-based study. Dev Med Child Neurol 2020;62(6):723-8. PMID 31701525
- 26
- Farkas E, Tomé FM, Fardeau M, Arsénio-Nunes ML, Dreyfus P, Diebler MF. Histochemical and ultrastructural study of muscle biopsies in three cases of dystrophia myotonica in the newborn child. J Neurol Sci 1974;21:273-88. PMID 4150367
- 27
- Fu YH, Pizzuti A, Fenwick RG Jr, et al. An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science 1992;255:1256-8. PMID 1546326
- 28
- Gagnon C, Kierkegaard M, Blackburn C, et al. Participation restriction in childhood phenotype of myotonic dystrophy type 1: a systematic retrospective chart review. Dev Med Child Neurol 2017;59(3):291-6. PMID 27671786
- 29
- Gagnon C, Noreau L, Moxley RT, et al. Towards an integrative approach to the management of myotonic dystrophy type 1. J Neurol Neurosurg Psychiatry 2007;78(8):800-6. PMID 17449544
- 30
- Gardiner CF. A case of myotonia congenita. Arch Pediatr 1901;18:925.
- 31
- Gourdon G, Meola G. Myotonic dystrophies: state of the art of new therapeutic developments for the CNS. Front Cell Neurosci 2017;11:101. PMID 28473756
- 32
- Hale MA, Bates K, Provenzano M, Johnson NE. Dynamics and variability of transcriptomic dysregulation in congenital myotonic dystrophy during pediatric development. Hum Mol Genet 2022;32(9):1413-28. PMID 36222125
- 33
- Harper PS. Congenital myotonic dystrophy in Britain: I. Clinical aspects. Arch Dis Child 1975;50(7):505-13. PMID 1101835
- 34
- Heatwole C, Luebbe E, Rosero S, et al. Mexiletine in myotonic dystrophy type 1: A randomized, double-blind, placebo-controlled trial. Neurology 2021;96(2):e228-40. PMID 33046619
- 35
- Ho G, Carey KA, Cardamone M, Farrar MA. Myotonic dystrophy type 1: clinical manifestations in children and adolescents. Arch Dis Child 2019;104(1):48-52. PMID 29871899
- 36
- Ho G, Cardamone M, Farrar M. Congenital and childhood myotonic dystrophy: Current aspects of disease and future directions. World J Clin Pediatr 2015;4(4):66-80. PMID 26566479
- 37
- Howe SJ, Ladipus D, Hull M, Yeaw J, Stevenson T, Sampson JB. Healthcare resource utilization, total costs, and comorbidities among patients with myotonic dystrophy using U.S. insurance claims data from 2012 to 2019. Orphanet J Rare Dis 2022;17(1):79. PMID 35197080
- 38
- Horrigan J, Gomes TB, Snape M, et al. A phase 2 study of AMO-02 (tideglusib) in congenital and childhood-onset myotonic dystrophy type 1 (DM1). Pediatr Neurol 2020;112:84-93. PMID 32942085
- 39
- Johnson NE, Aldana EZ, Angeard N, et al. Consensus-based care recommendations for congenital and childhood-onset myotonic dystrophy type 1. Neurol Clin Pract 2019;9(5):443-54. PMID 31750030
- 40
- Johnson NE, Butterfield R, Berggren K, et al. Disease burden and functional outcomes in congenital myotonic dystrophy: a cross-sectional study. Neurology 2016a;87(2):160-7. PMID 27306634
- 41
- Joosten IBT, Hellebrekers DMEI, de Greef BTA, et al. Parental repeat length instability in myotonic dystrophy type 1 pre- and protomutations. Eur J Hum Genet 2020;28(7):956-62. PMID 32203199
- 42
- Karpati G, Carpenter S, Watters GV. Infantile myotonic dystrophy: histochemical and electron microscopic features in skeletal muscle. Neurology 1973;23:1066-77. PMID 4795420
- 43
- Kim HN, Cho YK, Cho JH, Yang EM, Song ES, Choi YY. Transient complete atrioventricular block in a preterm neonate with congenital myotonic dystrophy: Case report. J Korean Med Sci 2014;29:879-83. PMID 24932094
- 44
- Klein AF, Dastidar S, Furling D, Chuah MK. Therapeutic approaches for dominant muscle diseases: highlight on myotonic dystrophy. Curr Gene Ther 2015;15(4):329-37. PMID 26122101
- 45
- Kroksmark AK, Stridh ML, Ekström AB. Long-term follow-up of motor function and muscle strength in the congenital and childhood forms of myotonic dystrophy type 1. Neuromuscul Disord 2017;27(9):826-35. PMID 28673557
- 46
- Kuo HC, Hsiao KM, Chen CJ, Hsieh YC, Huang CC. Brain magnetic resonance image changes in a family with congenital and classic myotonic dystrophy. Brain Dev 2005;27:291-6. PMID 15862193
- 47
- Lagrue E, Dogan C, De Antonio M, et al. A large multicenter study of pediatric myotonic dystrophy type 1 for evidence-based management. Neurology 2019;92(8):e852-65. PMID 30659139
- 48
- Lanni S, Pearson CE. Molecular genetics of congenital myotonic dystrophy. Neurobiol Dis 2019;132:104533. PMID 31326502
- 49
- Lindeblad G, Kroksmark AK, Ekström AB. Cognitive and adaptive functioning in congenital and childhood forms of myotonic dystrophy type 1: a longitudinal study. Dev Med Child Neurol 2019;61(10):1214-20. PMID 30706460
- 50
- López-Martínez A, Soblechero-Martín P, De-La-puente-ovejero L, Nogales-Gadea G, Arechavala-Gomeza V. An overview of alternative splicing defects implicated in myotonic dystrophy type i. Genes (Basel) 2020;11(9):1-27. PMID 32971903
- 51
- Maagdenberg SJM, Klinkenberg S, van den Berg JS, et al. Impact of gastrointestinal and urological symptoms in children with myotonic dystrophy type 1. Neuromuscul Disord 2024;35:1-7. PMID 38184901
- 52
- Mahadevan M, Tsilfidis C, Sabourin L, et al. Myotonic dystrophy mutation: an unstable CTG repeat in the 3’ untranslated region of the gene. Science 1992;255:1253-5. PMID 1546325
- 53
- Marsh S, Hanson B, Wood MJA, Varela MA, Roberts TC. Application of CRISPR-Cas9-mediated genome editing for the treatment of myotonic dystrophy type 1. Mol Ther 2020;28(12):2527-39. PMID 33171139
- 54
- Martorell L, Cobo AM, Baiget M, Naudo M, Poza JJ, Parra J. Prenatal diagnosis in myotonic dystrophy type 1. Thirteen years of experience: implications for reproductive counseling in DM1 families. Prenat Diagn 2007;27(1):68-72. PMID 17154336
- 55
- Mateos-Aierdi AJ, Goicoechea M, Aiastui A, et al. Muscle wasting in myotonic dystrophies: a model of premature aging. Front Aging Neurosci 2015;7:125. PMID 26217220
- 56
- Meola G, Cardani R. Myotonic dystrophies: an update on clinical aspects, genetic, pathology, and molecular pathomechanisms. Biochim Biophys Acta 2015;1852:594-606. PMID 24882752
- 57
- Morales F, Corrales E, Zhang B, et al. Myotonic dystrophy type 1 (DM1) clinical subtypes and CTCF site methylation status flanking the CTG expansion are mutant allele length-dependent. Hum Mol Genet 2022;31(2):262–74. PMID 34432028
- 58
- Morales F, Vásquez M, Cuenca P, et al. Parental age effects, but no evidence for an intrauterine effect in the transmission of myotonic dystrophy type 1. Eur J Hum Genet 2015;23(5):646-53. PMID 25052313
- 59
- Moxley RT. Myotonic disorders in childhood: diagnosis and treatment. J Child Neurol 1997;12:116-29. PMID 9075021
- 60
- Mutchnick IS, Thatikunta MA, Gump WC, Stewart DL, Moriarty TM. Congenital myotonic dystrophy: ventriculomegaly and shunt considerations for the pediatric neurosurgeon. Childs Nerv Syst 2016;32(4):609-16. PMID 26747623
- 61
- Nakamori M, Shimizu H, Ogawa K, et al. Cell type-specific abnormalities of central nervous system in myotonic dystrophy type 1. Brain Commun 2022;4(3):fcac154. PMID 35770133
- 62
- Okkersen K, Monckton DG, Le N, Tuladhar AM, Raaphorst J, van Engelen BGM. Brain imaging in myotonic dystrophy type 1: a systematic review. Neurology 2017;89(9):960-9. PMID 28768849
- 63
- Pascual-Gilabert M, López-Castel A, Artero R. Myotonic dystrophy type 1 drug development: A pipeline toward the market. Drug Discov Today 2021;26(7):1765-72. PMID 33798646
- 64
- Patel N, Berggren KN, Hung M, et al. Neurobehavioral phenotype of children with congenital myotonic dystrophy. Neurology 2024;102(5):e208115. PMID 38359368
- 65
- Peric S, Pesovic J, Savic-Pavicevic D, Stojanovic VR, Meola G. Molecular and clinical implications of variant repeats in myotonic dystrophy type 1. Int J Mol Sci 2022;23(1):354. PMID 35008780
- 66
- Pettersson OJ, Aagaard L, Jensen TG, Damgaard CK. Molecular mechanisms in DM1 - a focus on foci. Nucleic Acids Res 2015;43(4):2433-41. PMID 25605794
- 67
- Provenzano C, Cappella M, Valaperta R, et al. CRISPR/cas9-mediated deletion of CTG expansions recovers normal phenotype in myogenic cells derived from myotonic dystrophy 1 patients. Mol Ther Nucleic Acids 2017;9:337-48. PMID 29246312
- 68
- Pruzanski W. Variants of myotonic dystrophy in pre-adolescent life: The syndrome of myotonic dysembryoplasia. Brain 1966;89:563-8. PMID 5950778
- 69
- Quigg KH, Berggren KN, McIntyre M, et al. 12-month progression of motor and functional outcomes in congenital myotonic dystrophy. Muscle Nerve 2020:384-91. PMID 33341951
- 70
- Redman JB, Fenwick RG Jr, Fu YH, Pizzuti A, Caskey CT. Relationship between parental trinucleotide CTG repeat length and severity of myotonic dystrophy in the offspring. JAMA 1993;269:1960-5. PMID 8464127
- 71
- Romigi A. Clinical guide for the diagnosis and follow-up of myotonic dystrophy type 1, MD1 or Steinert’s disease: sleepiness and role of Epworth Sleepiness Scale. Neurologia 2020;35(3). PMID 32693949
- 72
- Saito Y, Matsumura K, Kageyama M, et al. Impact of prematurity and the CTG repeat length on outcomes in congenital myotonic dystrophy. BMC Res Notes 2020;13(1):4-9. PMID 32703309
- 73
- Sarnat HB. Vimentin and desmin in maturing skeletal muscle and developmental myopathies. Neurology 1992;42:1616-24. PMID 1641160
- 74
- Sarnat HB, O’Connor T, Byrne PA. Clinical effects of myotonic dystrophy on pregnancy and the neonate. Arch Neurol 1976;33:459-65. PMID 779728
- 75
- Sarnat HB, Silbert SW. Maturational arrest of fetal muscle in neonatal myotonic dystrophy. A Pathologic study of four cases. Arch Neurol 1976;33:466-74. PMID 132914
- 76
- Sjögreen L, Mårtensson Å, Ekström AB. Speech characteristics in the congenital and childhood-onset forms of myotonic dystrophy type 1. Int J Lang Commun Disord 2018;53(3):576-83. PMID 29327796
- 77
- Sumi M, Kusumoto T, Tagawa M, et al. Two infantile cases of congenital myotonic dystrophy with cholelithiasis/cholestasis. Pediatr Int 2005;47:586-8. PMID 16190971
- 78
- Sweere DJJ, Moelands SVL, Klinkenberg S, Leenen L, Hendriksen JGM, Braakman HMH. Cognitive phenotype of childhood myotonic dystrophy type 1: a multicenter pooled analysis. Muscle Nerve 2023;68(1):57-64. PMID 371294357
- 79
- Swift TR, Ignacio OJ, Dyken PR. Neonatal dystrophia myotonica: electrophysiologic studies. Am J Dis Child 1975;129:734-7. PMID 808120
- 80
- Tachi N, Kozuka N, Ohya K, Chiba S, Kikuchi K. CTG repeat size and histologic findings of skeletal muscle from patients with congenital myotonic dystrophy. J Child Neurol 1996;11:430-2. PMID 9120218
- 81
- Tanaka Y, Suzuki Y, Shimozawa N, Nanba E, Kondo N. Congenital myotonic dystrophy: report of paternal transmission. Brain Dev 2000;22:132-4. PMID 10722967
- 82
- Thomas JD, Sznajder ŁJ, Bardhi O, et al. Disrupted prenatal RNA processing and myogenesis in congenital myotonic dystrophy. Genes Dev 2017;31(11):1122-33. PMID 28698297
- 83
- Thornton CA, Wang E, Carrell EM. Myotonic dystrophy: approach to therapy. Curr Opin Genet Dev 2017;44:135-40. PMID 28376341
- 84
- Tominaga K, Hayashi YK, Goto K, et al. Congenital myotonic dystrophy can show congenital fiber type disproportion pathology. Acta Neuropathol 2010;119(4):481-6. PMID 20179953
- 85
- van den Bersselaar LR, Heytens L, Silva HCA, et al. European Neuromuscular Centre consensus statement on anaesthesia in patients with neuromuscular disorders. Eur J Neurol 2022;29(12):3486–507. PMID 35971866
- 86
- Vanier TM. Dystrophia myotonica in childhood. Br Med J 1960;2:1284-8. PMID 13780165
- 87
- Veyckemans F, Scholtes JL. Myotonic dystrophies type 1 and 2: anesthetic care. Paediatr Anaesth. 2013 Sep;23(9):794-803. PMID 23384336
- 88
- Vinereanu D, Bajaj BP, Fenton-May J, Rogers MT, Madler CF, Fraser AG. Subclinical cardiac involvement in myotonic dystrophy manifesting as decreased myocardial Doppler velocities. Neuromuscul Disord 2004;14:188-94. PMID 15036328
- 89
- Visconti VV, Centofanti F, Fittipaldi S, Macrì E, Novelli G, Botta A. Epigenetics of myotonic dystrophies: A minireview. Int J Mol Sci 2021;22(22):12594. PMID 34830473
- 90
- Watters GV, Williams TW. Early onset myotonic dystrophy. Arch Neurol 1967;17:137-52. PMID 6028243
- 91
- Wesstrom G, Bensch J, Schollin J. Congenital myotonic dystrophy. Incidence, clinical aspects and early prognosis. Acta Pediatr Scand 1986;75:849-54. PMID 3564952
- 92
- Yee C, Choi SJ, Oh SY, Ki CS, Roh CR, Kim JH. Clinical characteristics of pregnancies complicated by congenital myotonic dystrophy. Obstet Gynecol Sci 2017;60(4):323-8. PMID 28791262
- 93
- Yum K, Wang ET, Kalsotra A. Myotonic dystrophy: disease repeat range, penetrance, age of onset, and relationship between repeat size and phenotypes. Curr Opin Genet Dev 2017;44:30-7. PMID 28213156
- 94
- Zeesman S, Carson N, Whelan DT. Paternal transmission of the congenital form of myotonic dystrophy type 1: a new case and review of the literature. Am J Med Genet 2002;107:222-6. PMID 11807903
Contributors
All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.
Author
-
Jean K Mah MD
Dr. Mah of the University of Calgary has no relevant financial relationships to disclose.
See Profile
Editor
-
Harvey B Sarnat MD FRCPC MS
Dr. Sarnat of the University of Calgary has no relevant financial relationships to disclose.
See Profile
Former Authors
- Harvey B Sarnat MD FRCPC MS
Patient Profile
- Age range of presentation
-
- 0 to 01 month
- Sex preponderance
-
- male=female
- Heredity
-
- autosomal dominant trait
- Population groups selectively affected
-
- none selectively affected
- Occupation groups selectively affected
-
- none selectively affected
ICD & OMIM codes
- ICD-11
-
- Myotonic dystrophy: 8C71.0
- Myotonia congenita: 8C71.2
- OMIM
-
- Dystrophia myotonica 1: #160900
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