Myotonic Dystrophy

Key Points:

  • Myotonia and weakness are the most common findings
  • Congenital and adult onset forms (DM1 & DM2)
  • Autosomal Dominant inheritance

Description:

  Myotonic dystrophies (dystrophia myotonica, DM) are a set of diseases that are inherited in an autosomal dominant pattern and can affect multiple organ systems. The classic clinical presentation includes myotonia, muscular dystrophy, cardiac conduction abnormalities, cataracts and endocrine disorders (Meola, 2014). There are two types within the “classic”, type 1 DM, also known as Steinert’s disease. There is significant variability in the presentation of DM1 with nearly 75% of patients not having any symptoms until adulthood but a subset of DM1 patients may present with the severe congenital form (Thornton, 2014). DM2 is a much milder form with typical onset in adulthood. 

Epidemiology:

  Wide varieties of incidence have been reported and the true incidence is difficult to determine due to the fact that widespread screening has not been performed and clinical presentation varies. The reported values range from 1:3500 to 1:16000 (Karol, 2014; Canavese, 2009). Canavese et al. found an equal male to female ratio in their population. 

Clinical Findings:

  Presentation of DM1 can range from relatively asymptomatic individuals with adult onset myotonia to a severe life threatening congenital form (Turner, 2014). Myotonia, the failure of voluntary muscle to relax when stimulation is withdrawn, is the most common symptom. Grip myotonia is often the initial finding (Turner, 2014) but it often also affects the muscles of the face, tongue and limbs (Karol, 2014). Significant hypotonia in the severe congenital cases can lead to respiratory weakness that requires ventilator support at birth (Canavese, 2009).

  Many individuals will have delayed onset of ambulation due to either weakness or deformities such as talipes equinovarus (clubfoot) that can be present. Canavese et al. reported scoliosis to be present in 30% of patients that they reviewed but noted that it may be more prevalent in older patient populations they did not examine. (Figure 1)  Cervical lordosis due to weakness of the sternocleidomastoid musculature may also be present. 
  
  The faces of patients with this condition are often described as expressionless and have ptosis and significant temporal narrowing. Often times these individuals resemble each other more than family members (Canavese 2009). In the severe congenital form there is often significant cognitive impairment. Patients may have daytime hypersomnolence and generalized disruption of their sleep cycle (Thornton, 2014). Other systemic abnormalities include insulin resistance, GI disturbance, hypogonadism, and abnormal liver function. 

  Cataracts before the age of 55 with any signs of muscle weakness should be a red flag for DM work up. 

Imaging Studies:

  Routine radiographic evaluation is unnecessary unless there is clinical concern for a specific deformity. PA and lateral thoracolumbar spine films are indicated if there is concern for scoliosis. Periodic monitoring of scoliosis is necessary as it may progress given the neuromuscular origin.

Etiology:

  The genetic defect that leads to DM1 is a CTG trinucleotide repeat of the myotonic dystrophy protein kinase gene on chromosome 19 which codes for myosin kinase expressed on skeletal muscle (Meola, 2014). The number of repeats corresponds to the phenotypic severity of the disease. Genetic anticipation is often seen in this condition with the number of repeats increasing by up to 200 when transmitted from mother to child (Thornton, 2014). 

  Type 2 is characterized by a CCTG repeat on chromosome 3 and does not have a severe congenital form (Karol, 2014). Additionally, genetic anticipation does not appear to occur in this population (Thornton, 2014). 

Treatment:

  Bracing can be helpful as a temporizing means to assist with treatment of scoliosis until children are older, however are less efficacious than bracing in idiopathic scoliosis. Additionally, given the fact that this is a neuromuscular scoliosis they are best served ultimately with a posterior spinal fusion for large, progressive curves (Themistocleous, 2009). 

  Canavese et al. reported that they treated all of their clubfeet surgically without any attempt at casting and had 1 recurrence (Canavese, 2009). Surgical intervention was noted to improve the ability to ambulate.  

  Medical treatment for weakness, including DHEA, IGF-1 or creatine has not been found to be effective. Routine exercise is not harmful and is often recommended Some anti-myotonia drugs like mexiletine have been found to be helpful (Turner, 2014). Routine evaluation by patient’s primary physician is important to monitor for cardiac and endocrine disturbances. 

  Gene therapies are being developed to target the known defects in myotonic dystrophy but human studies are lagging behind animal models (Turner, 2014; Thornton, 2014).

Complications:

  Respiratory failure is the most common cause of death in this population and results from severe hypotonia. It is responsible for up to 40% of early mortalities (Turner, 2014). Cardiac arrhythmias are also relatively common and can lead to sudden cardiac death. 

  Care must be taken to avoid aggravation of respiratory depression or cardiac abnormalities during surgical intervention and the anesthesia team must plan accordingly (Themistocleous, 2004; Canavese, 2009).

References:

  1. Canavese F, Sussman M. Orthopaedic Manifestations of Congenital Myotonic Dystrophy During Childhood and Adolescence. J Pediatr Orthop. 2009; 29: 208-213. 
  2. Karol L. In: Herring JA, ed. Tachdjian’s Pediatric Orthopaedics. 5th ed. Philadelphia, PA: Elsevier; 2014: 308-327.
  3. Meola G, Cardani R. Myotonic dystrophies: An update on clinical aspects, genetic, pathology, and molecular pathomechanisms. Biochemica et Biophysica Acta. 2015; 594-606. 
  4. Themistocleous G, Sapkas G, Papagelopoulos P, et al. Scoliosis in Steinert syndrome: a case report.  The Spine Journal. 2005; 5: 212-216. 
  5. Thornton C. Myotonic Dystrophy. Neurologic Clinics. 2014; 32(3): 705-719. 
  6. Turner C, Hilton-Jones D. Myotonic dystrophy: diagnosis, management and new therapies. Current Opinions in Neurology. 2014; 27: 599-606.

Figures and Tables:


Figure 1: A 15-month-old with myotonic dystrophy was treated for clubfoot deformity and then returned to clinic with scoliosis.  A casting and bracing program was then initiated to manage the scoliosis. (Image courtesy of Jeff Martus MD)

Top Contributors:

Vince Prusick MD
Jeff Martus MD