Myotonic Dystrophies Type 1 and 2: A Summary on Current Aspects

doi:10.1016/j.spen.2006.06.002

Seminars in Pediatric Neurology

Volume 13, Issue 2, June 2006, Pages 71-79

https://doi.org/10.1016/j.spen.2006.06.002 Get rights and content

Myotonic dystrophies (DMs) encompass at least 2 forms: myotonic dystrophy type 1 and 2. In general, DMs are late-onset autosomal dominant disorders characterized by a variety of multisystemic features including myotonia, muscular dystrophy, cardiac conduction defects, dilated cardiomyopathy, posterior iridescent cataracts, frontal balding, insulin-resistance and disease-specific serological abnormalities such as gamma-glutamyltransferase and creatine kinase elevations, hyperglycemia, hypotestosteronism, and reduced immunoglobulin (Ig) G and IgM levels. Beyond the adult forms, in the classic DM1, a congenital form and an early-onset form is recognized. Here we summarize current aspects of the myotonic dystrophy pathogenesis and review the core features of both types of myotonic dystrophies, including the congenital DM1.

Section snippets

Molecular Genetics of DM Type 1

In 1992, DM type 1 (DM1) on chromosome 19 was shown to be caused by an expanded CTG repeat in the 3′ untranslated region of the dystrophia myotonica-protein kinase (DMPK) gene.3, 4, 12, 13, 14, 15 The incidence of DM1 is 13:100,000; the prevalence is 2 to 5/100,000 in the congenital form 1: 3500.3, 4 The CTG expansions in DM1 differ from 80 to more than 4,000 repeats in affected patients, with clinically unaffected patients having repeats of 50 to 100 CTGs. Somatic instability has been reported

DM1

Manifestation varies from the pre-/postnatal period to adulthood: within the broad spectrum of clinical symptoms, there are some distinct phenotypes according to the age of onset and the number of CTG repeats. Genotype phenotype correlations revealed a slight increase of CTG repeats in the juvenile-adult form, a stronger increase in patients with childhood onset, and the largest CTG repeats (>1,500) in congenital myotonic dystrophy.3, 4, 25 Clinicians should be able to recognize these different

Monitoring and Therapy of All Types of DM

Monitoring should include conduction studies, ultrasound of the heart, and respiratory function analysis. Although there is no causative therapy available so far, symptomatic therapy should include the following.39, 40, 41, 42

In congenital DM1, symptomatic therapy should include (1) stabilization of respiratory and feeding difficulties, (2) orthopedic surgery if necessary, (3) physiotherapy, (4) pulmonary and cardiac investigations, (5) treatment of motor and mental handicaps, and (6)

Outlook

Although myotonic dystrophy was noticed around 100 years ago, we still become aware of new aspects and types of this puzzling multisystemic disorder. By further uncovering the RNA pathomechanism and creating new RNA therapy strategies, specific tools may be found for treatment of these disorders.

References (42)

B. Udd et al.
Proximal myotonic dystrophy—A family with autosomal dominant muscular dystrophy, cataracts, hearing loss and hypogonadism: Heterogeneity of proximal myotonic syndromes?
Neuromuscul Disord
(1997)
J.W. Day et al.
Clinical and genetic characteristics of a five-generation family with a novel form of myotonic dystrophy (DM2)
Neuromuscul Disord
(1999)
J.W. Day et al.
RNA pathogenesis of the myotonic dystrophies
Neuromuscul Disord
(2005)
L.L. Bachinski et al.
Confirmation of DM2 (CCTG)n expansion mutation in PROMM/PDM patients of different European origins: A single shared haplotype indicates ancestral founder effects
Am J Hum Genet
(2003)
C.L. Liquori et al.
Myotonic dystrophy type 2: Human founder haplotype and evolutionary conservation of the repeat tract
Am J Hum Genet
(2003)
K. Rais-Bahrami et al.
Persistent pulmonary hypertension in newborn infants with congenital myotonic dystrophy
J Pediatr
(1994)
B.G. van Engelen et al.
123rd ENMC international workshop: Management and Therapy in Myotonic Dystrophy, 6-8 February 2004, Naarden, The Netherlands
Neuromuscul Disord
(2005)
B. Udd et al.
140th ENMC International Workshop: Myotonic Dystrophy DM2/PROMM and other myotonic dystrophies with guidelines on management
Neuromuscul Disord
(2006)
H. Steinert
Myopathologische Beiträge 1. Über das klinische und anatomische Bild des Muskelschwunds der Myotoniker
Dtsch Zeitschr Nervenheilk
(1909)
F.E. Batten et al.
Myotonia atrophica
Brain
(1909)

P.S. Harper

Major problems in neurology, in Myotonic Dystrophy

(2001)

P.S. Harper et al.

Myotonic dystrophy

H. Curschmann

Über familiäre atrophische Myotonie

Dtsch Zeitschr Nervenheilk

(1912)

H. Curschmann

Myotonische Dystrophie (atrophische myotonie)

B. Fleischer

Über myotonische Dystrophie mit Katarakt

Graefes Arch Klin Ophthalmol

(1918)

K. Ricker et al.

Proximal myotonic myopathy: A new dominant disorder with myotonia, muscle weakness, and cataracts

Neurology

(1994)

C.A. Thornton et al.

Myotonic dystrophy with no trinucleotide repeat expansion

Ann Neurol

(1994)

C. Aslanidis et al.

Cloning of the essential myotonic dystrophy region and mapping of the putative defect

Nature

(1992)

J. Buxton et al.

Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy

Nature

(1992)

H.G. Harley et al.

Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy

Nature

(1992)

M. Mahadevan et al.

Myotonic dystrophy mutation: An unstable CTG repeat in the 3′ untranslated region of the gene

Science

(1992)

Cited by (105)

Orthopedic Surgery in Neuromuscular Disorders
2021, Neuromuscular Disorders: Treatment and Management
Patients with neuromuscular disorders often have associated musculoskeletal conditions that affect the spine and the upper and lower extremities, and orthopedic treatment often is needed to allow improved function and prevention of deformities. Patients with any of the muscular dystrophies often need treatment of scoliosis and lower extremity contractures. Treatment with steroids has resulted in decreased bone mineral density resulting in fractures of both the extremities and spine. Patients with Charcot-Marie-Tooth disease often develop cavovarus foot deformities that may need treatment to allow continued ambulation. This chapter discusses the most common musculoskeletal deformities in children with neuromuscular disorders and the recommended orthopedic treatment.
Lesion distribution and substrate of white matter damage in myotonic dystrophy type 1: Comparison with multiple sclerosis
2021, NeuroImage: Clinical
Myotonic Dystrophy type 1 (DM1) is an autosomal dominant condition caused by expansion of the CTG triplet repeats within the myotonic dystrophy protein of the kinase (DMPK) gene. The central nervous system is involved in the disease, with multiple symptoms including cognitive impairment. A typical feature of DM1 is the presence of widespread white matter (WM) lesions, whose total volume is associated with CTG triplet expansion. The aim of this study was to characterize the distribution and pathological substrate of these lesions as well as the normal appearing WM (NAWM) using quantitative magnetization transfer (qMT) MRI, and comparing data from DM1 patients with those from patients with multiple sclerosis (MS). Twenty-eight patients with DM1, 29 patients with relapsing-remitting MS, and 15 healthy controls had an MRI scan, including conventional and qMT imaging. The average pool size ratio (F), a proxy of myelination, was computed within lesions and NAWM for every participant. The lesion masks were warped into MNI space and lesion probability maps were obtained for each patient group. The lesion distribution, total lesion load and the tissue-specific mean F were compared between groups. The supratentorial distribution of lesions was similar in the 2 patient groups, although mean lesion volume was higher in MS than DM1. DM1 presented higher prevalence of anterior temporal lobe lesions, but none in the cerebellum and brainstem. Significantly reduced F values were found within DM1 lesions, suggesting a loss of myelin density. While F was reduced in the NAWM of MS patients, it did not differ between DM1 and controls. Our results provide further evidence for a need to compare histology and imaging using new MRI techniques in DM1 patients, in order to further our understanding of the underlying disease process contributing to WM disease.
Clinical guide for the diagnosis and follow-up of myotonic dystrophy type 1, MD1 or Steinert's disease
2020, Neurologia
La enfermedad de Steinert o distrofia miotónica tipo 1 (DM1), (OMIM 160900) es la miopatía más prevalente en el adulto. Es una enfermedad multisistémica con alteración de prácticamente todos los órganos y tejidos y una variabilidad fenotípica muy amplia, lo que implica que deba ser atendida por diferentes especialistas que dominen las alteraciones más importantes. En los últimos años se ha avanzado de manera exponencial en el conocimiento de la enfermedad y en su manejo. El objetivo de la guía es establecer recomendaciones para el diagnóstico, el pronóstico, el seguimiento y el tratamiento de las diferentes alteraciones de la DM1.
Esta guía de consenso se ha realizado de manera multidisciplinar. Se ha contado con neurólogos, neumólogos, cardiólogos, endocrinólogos, neuropediatras y genetistas que han realizado una revisión sistemática de la literatura.
Se recomienda realizar un diagnóstico genético con cuantificación precisa de tripletes CTG. Los pacientes con DM1 deben seguir control cardiológico y neumológico de por vida. Antes de cualquier cirugía con anestesia general debe realizarse una evaluación respiratoria. Debe monitorizarse la presencia de síntomas de disfagia periódicamente. Debe ofrecerse consejo genético a los pacientes con DM1 y a sus familiares.
La DM1 es una enfermedad multisistémica que requiere un seguimiento en unidades especializadas multidisciplinares.
Steinert's disease or myotonic dystrophy type 1 (MD1), (OMIM 160900), is the most prevalent myopathy in adults. It is a multisystemic disorder with dysfunction of virtually all organs and tissues and a great phenotypical variability, which implies that it has to be addressed by different specialities with experience in the disease. The knowledge of the disease and its management has changed dramatically in recent years. This guide tries to establish recommendations for the diagnosis, prognosis, follow-up and treatment of the complications of MD1.
Consensus guide developed through a multidisciplinary approach with a systematic literature review. Neurologists, pulmonologists, cardiologists, endocrinologists, neuropaediatricians and geneticists have participated in the guide.
The genetic diagnosis should quantify the number of CTG repetitions. MD1 patients need cardiac and respiratory lifetime follow-up. Before any surgery under general anaesthesia, a respiratory evaluation must be done. Dysphagia must be screened periodically. Genetic counselling must be offered to patients and relatives.
MD1 is a multisystemic disease that requires specialised multidisciplinary follow-up.
Clinical guide for the diagnosis and follow-up of myotonic dystrophy type 1, MD1 or Steinert's disease
2019, Medicina Clinica
La enfermedad de Steinert o distrofia miotónica tipo 1 (DM1), (OMIM 160900) es la miopatía más prevalente en el adulto. Es una enfermedad multisistémica con alteración de prácticamente todos los órganos y tejidos y una variabilidad fenotípica muy amplia, lo que implica que deba ser atendida por diferentes especialistas que dominen las alteraciones más importantes. En los últimos años se ha avanzado de manera exponencial en el conocimiento de la enfermedad y en su manejo. El objetivo de la guía es establecer recomendaciones para el diagnóstico, el pronóstico, el seguimiento y el tratamiento de las diferentes alteraciones de la DM1.
Esta guía de consenso se ha realizado de manera multidisciplinar. Se ha contado con neurólogos, neumólogos, cardiólogos, endocrinólogos, neuropediatras y genetistas que han realizado una revisión sistemática de la literatura.
Se recomienda realizar un diagnóstico genético con cuantificación precisa de tripletes CTG. Los pacientes con DM1 deben seguir control cardiológico y neumológico de por vida. Antes de cualquier cirugía con anestesia general debe realizarse una evaluación respiratoria. Debe monitorizarse la presencia de síntomas de disfagia periódicamente. Debe ofrecerse consejo genético a los pacientes con DM1 y a sus familiares.
La DM1 es una enfermedad multisistémica que requiere un seguimiento en unidades especializadas multidisciplinares.
Steinert's disease or myotonic dystrophy type 1 (MD1), (OMIM 160900), is the most prevalent myopathy in adults. It is a multisystemic disorder with dysfunction of virtually all organs and tissues and a great phenotypical variability, which implies that it has to be addressed by different specialities with experience in the disease. The knowledge of the disease and its management has changed dramatically in recent years. This guide tries to establish recommendations for the diagnosis, prognosis, follow-up and treatment of the complications of MD1.
Consensus guide developed through a multidisciplinary approach with a systematic literature review. Neurologists, pulmonologists, cardiologists, endocrinologists, neuropaediatricians and geneticists have participated in the guide.
The genetic diagnosis should quantify the number of CTG repetitions. MD1 patients need cardiac and respiratory lifetime follow-up. Before any surgery under general anaesthesia, a respiratory evaluation must be done. Dysphagia must be screened periodically. Genetic counselling must be offered to patients and relatives.
MD1 is a multisystemic disease that requires specialised multidisciplinary follow-up.
Hypotonic syndrome manifestation of neuromuscular hereditary disease in infants
2018, Revista Medica Clinica Las Condes
La hipotonía es un signo no específico definido como una disminución de la resistencia al movimiento pasivo de las articulaciones, la cual comprende un grupo amplio y heterogéneo de condiciones que afectan tanto al sistema nervioso central como periférico. En la orientación clínica sigue siendo crucial distinguir pacientes con o sin debilidad asociada y la diferenciación entre hipotonía central, periférica y mixta. A través de la historia clínica y examen físico es posible lograr esta distinción en cerca de la mitad de los casos, siendo las centrales las más frecuentes. Este artículo tiene como objetivo realizar una puesta al día en síndrome hipotónico del recién nacido y lactante menor (<2 años), con énfasis en las causas de origen neuromuscular hereditario, fundamentalmente en la evaluación clínica y enfoque diagnóstico.
Hypotonia is a non-specific sign defined as decrease resistence to passive joint's movement, wich comprises a broad and heterogeneous group of conditions that affect the central or peripheral nervous system. in the first clinical orientation it is still crucial to distinguish patients with oy without associated weakness and the differentiation between central, peripheral and mixed hypotonia. Through clinical history and physical examination it is possible to achieve this distinction in about half of the cases, with central causes being the most frequent. The objetive of this article is to make an update hypotonic syndrome in newborns and infants (less than 2 years), with emphasis on hereditary neuromuscular causes, focused on clinical evaluation and diagnosis approach.
Myopathies
2018, Essentials of Physical Medicine and Rehabilitation: Musculoskeletal Disorders, Pain, and Rehabilitation
Myopathy refers to diseases derived from the muscle. Myopathies have different causes and may have acute, subacute, or chronic clinical presentations. They are progressive but have different time courses and affect proximal or distal muscle groups; some of them also affect heart muscle, leading to cardiomyopathy. In an increasing number of myopathies, the genetic background and the abnormal or missing muscle proteins have been identified and are cornerstones for the diagnosis. Other important diagnostic features are high CK values and abnormalities on electrophysiologic examination and muscle biopsy. In a few myopathies—for example, inflammatory myopathies and lipid storage myopathies—specific pharmacologic treatment is available. Rehabilitation of patients with myopathy includes physical and occupational therapy as well as assistive and orthotic devices. Different exercise training can be recommended in all patients with myopathy.

View all citing articles on Scopus

: Supported in part by the German Network on Muscular Dystrophies (MD-NET, 01GM0302) funded by the German Ministry of Education and Research (BMBF, Bonn, Germany).

View full text

Myotonic Dystrophies Type 1 and 2: A Summary on Current Aspects

Section snippets

Molecular Genetics of DM Type 1

DM1

Monitoring and Therapy of All Types of DM

Outlook

Neuromuscul Disord

Neuromuscul Disord

Neuromuscul Disord

Am J Hum Genet

Am J Hum Genet

J Pediatr

Neuromuscul Disord

Neuromuscul Disord

Myopathologische Beiträge 1. Über das klinische und anatomische Bild des Muskelschwunds der Myotoniker

Dtsch Zeitschr Nervenheilk

Myotonia atrophica

Brain

Major problems in neurology, in Myotonic Dystrophy

Myotonic dystrophy

Über familiäre atrophische Myotonie

Dtsch Zeitschr Nervenheilk

Myotonische Dystrophie (atrophische myotonie)

Über myotonische Dystrophie mit Katarakt

Graefes Arch Klin Ophthalmol

Proximal myotonic myopathy: A new dominant disorder with myotonia, muscle weakness, and cataracts

Neurology

Myotonic dystrophy with no trinucleotide repeat expansion

Ann Neurol

Cloning of the essential myotonic dystrophy region and mapping of the putative defect

Nature

Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy

Nature

Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy

Nature

Myotonic dystrophy mutation: An unstable CTG repeat in the 3′ untranslated region of the gene

Science