Myotonic Dystrophy

Original Editor - Kehinde Fatola
Top Contributors - Ananya Bunglae Sudindar, Kehinde Fatola and Kim Jackson

Introduction[edit | edit source]

Myotonic dystrophy also known as dystrophia myotonica or myotonia atrophica, is an autosomal dominant hereditary multisystemic (eye, heart, brain, endocrine, gastrointestinal tract, uterus, skin) disease that is chronic, slow-progressing, and very variable. They present with the core features of myotonia, muscle weakness, and early onset cataracts. [1] [2]

Myotonic dystrophy (DM) is hereditary, affecting males and females almost equally and caused due to the expansions of repetitive DNA sequences, known as trinucleotide repeats. Symptoms may surface at any time between infancy to adulthood. DM causes general weakness, usually beginning in the muscles of the hands, feet, neck, or face and it progresses gradually to involve other muscle groups, including the heart and a wide range of other organ systems as well. A severe form of DM, congenital myotonic dystrophy, may be seen in babies of mothers who have DM. Congenital Myotonic Dystrophy can also be inherited through the gene of the father, although it was reported to be relatively rare. [3][2]

Types[edit | edit source]

There are two main types of myotonic dystrophy. [4]

Type 1 (DM1), also known as Steinert disease, is due to mutations (expansion) on the cytosine-thymine-guanine (CTG) triplet repeat in the DMPK gene on the long arm of Chromosome 19 and has a severe congenital form and a less-severe childhood-onset form as well as an adult-onset form. This disease in more common in the facial muscles, levator palpebrae superioris, temporalis, sternocleidomastoids, distal muscles of the forearm, hand intrinsic muscles, and ankle dorsiflexors.

Type 2 (DM2), also known as proximal myotonic myopathy (PROMM), is rarer and generally manifests with milder signs and symptoms than DM1 The specific defect is a repeat of the cytosine-cytosine-thymine-guanosine (CCTG) tetranucleotide in the ZNF9 gene on Chromosome 3.

Pathophysiology[edit | edit source]

Both DM1 and DM2, despite having genetic differences, share a common pathogenic mechanism. There is expansion of (CTG)n in the DMPK gene in DM1 and expansion of (CCTG)n in ZNF9/CNBP in DM2 and these expanded sequences are transcribed into RNA with repeats of CUG or CCUG. The mutant RNA forms clumps called nuclear foci which trap RNA binding proteins, leading to problems in splicing of other genes resulting in a range of clinical symptoms. In addition to splicing issues, factors such as changes in gene activity, protein production and micro-RNA function also play a role in the development of the disease. [5]

Clinical Presentation[edit | edit source]

Congenital Myotonic Dystrophy (CDM)[edit | edit source]
  •    Foetal-onset muscle and CNS involvement.
  •    Reduced foetal movement, polyhydramnios (excessive accumulation of amniotic fluid in the amniotic sac during pregnancy).
  •    Characteristic tented upper lip.
  •    Dysarthria, expressive aphasia.
  •    Hypotonia, respiratory involvement.
Mild Myotonic Dystrophy[edit | edit source]
  •    Mild weakness, myotonia, cataracts.
  •    Onset: 20 to 70 years.
  •    Normal lifespans.
Classic Myotonic Dystrophy[edit | edit source]
  •    Onset: 2nd to 4th decades.
  •    Myotonia, "warm-up phenomenon" (observable improvement in muscle stiffness and myotonia (delayed relaxation of muscles after contraction) with repeated muscle activity or exercise)
  •    Distal muscle weakness, impaired fine motor tasks.
  •    Myopathic face (facial appearance characterized by specific features associated with muscle weakness and wasting)
  •    Cardiac conduction abnormalities.
  •    Reduced lifespan compared to average lifespan.
Childhood Myotonic Dystrophy[edit | edit source]
  •    Onset around age 10.
  •    Learning difficulties, psychosocial problems.
  •    Dysarthria, hand muscle myotonia.
  •    Cardiac conduction abnormalities.
Myotonic Dystrophy Type II (DM2)[edit | edit source]
  •    Onset: Adulthood (median age 48 years).
  •    Early-onset cataracts.
  •    Varying grip myotonia, muscle weakness.
  •    Hearing loss, myofascial pain.
  •    Axial, proximal muscle weakness.
  •    Pain: abdominal, musculoskeletal, exercise related.

[6]

Some of the other possible symptoms include:

  • Communication and intellectual difficulties
  • Somnolence
  • Apathy
  • Deficit in executive functions
  • Depression
  • Fatigue.
    [7]

Management / Interventions[edit | edit source]

Like most other dystrophies, there's no known cure for MD and thus, management is generally symptomatic. Physiotherapy has been indicated to improve ROM, prevent disuse atrophy, conserving energy, avoiding re-injury, and enhancing functional abilities while decreasing disability. Some of which are:

  • Range of motion / stretching exercises
  • Aerobic exercise
  • Resistive exercises
  • Balance training
  • Orthosis may be recommended if there's an indication due to weak muscles

[7]

Differential Diagnosis[edit | edit source]


The video below provides an overview on pathology, clinical features and management of Myotonic Dystrophy: [8]

References[edit | edit source]

  1. Meola G. Myotonic dystrophy type 2: the 2020 update. Acta Myologica. 2020 Dec;39(4):222.
  2. 2.0 2.1 Turner, C; Hilton-Jones D. (2010). "The myotonic dystrophies: diagnosis and management". J Neurol Neurosurg Psychiatry 81 (4): 358–367.
  3. Orphanet Report Series - Prevalence of rare diseases: Bibliographic data – January 2022
  4. Dalton, Joline C.; Ranum, Laura PW; Day, John W. (1993-01-01). Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora JH; Bird, Thomas D.; Fong, Chin-To; Mefford, Heather C., eds. Myotonic Dystrophy Type 2. Seattle (WA): University of Washington, Seattle.
  5. Meola G, Cardani R. Myotonic dystrophies: An update on clinical aspects, genetic, pathology, and molecular pathomechanisms. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2015 Apr 1;1852(4):594-606.
  6. Vydra DG, Rayi A. Myotonic dystrophy. InStatPearls [Internet] 2022 Jun 27. StatPearls Publishing.
  7. 7.0 7.1 Myotonic Dystropy Foundation. Role of Physical Therapy in the Assessment and Management of Individuals with Myotonic Dystrophy. 2020
  8. Myotonic dystrophy - signs and symptoms, pathophysiology, treatment [Internet]. YouTube; 2022 . Available from: https://www.youtube.com/watch?v=6mwqWmc2WwQ