Why breathing is such an issue with Congenital Myotonic Dystrophy

Breathing is a huge and life threatening issue in myotonic dystrophy. An article recently shed some light on the reasons for this. Because of ethical issues its difficult to do live tests on humans. However, our fine researchers have created mice that have the congenital form of myotonic dystrophy. Through detailed analysis of the mice and there breathing they have isolated the issue to the neuropathology of several body systems. That means its not only the muscle issues but there are some nerve conduction issues involved as well. This information will help the drug companies as they design drugs to help not only the muscle issues but the nerves that serve to coordinate the breathing mechanisms. As a drug is introduced testing it on these mice would see if it will help the respiratory function.

Results from the Study
Because it is not feasible to take biopsies of the nervous system from
patients with DM1 for histological examinations, animal models are
indispensable for the study of the mechanisms underlying respiratory
failure in this disease. In this study, the authors test the respiratory function
and analyze the structures involved in respiratory function in DMSXL
transgenic mice, an established animal model for congenital DM1 (the severest
form of the disease, which develops at birth) that carries a very long CTG
repeat in the DMPK gene. Statistical analysis of breathing function
measurements shows that DMSXL mice have impaired respiratory function.
Histological and morphometric analyses reveal pathological changes in the
diaphragmatic neuromuscular junctions and muscle fibers of DMSXL mice and
a significant decrease in the number of unmyelinated phrenic afferents. By
contrast, DMSXL mice exhibit no significant neuronopathy in either cervical
phrenic motor neurons or brainstem respiratory neurons.
Implications and future directions
By shedding new light on the cellular mechanisms of respiratory failure in
DM1, these findings improve understanding of the main cause of death in
congenital DM1. The denervation and the pathological changes of the
diaphragmatic neuromuscular junctions observed in DMSXL mice suggest that
a breakdown in communication between the diaphragmatic muscle fibers and
the nerve endings might be the main cause of respiratory failure; the loss of
phrenic unmyelinated afferents suggests that altered regulation of breathing is
also involved. As well as contributing towards the understanding of respiratory
failure in DM1, these findings suggest that the evaluation of respiratory
parameters in DMSXL mice by non-invasive pressure plethysmography could
be used to evaluate the effect of potential therapies. Moreover, future analyses
of gene expression in DMSXL mice might contribute to our understanding of
the molecular mechanisms involved in respiratory impairment.


What causes the Congenital Form of Myotonic Dystrophy

This has always been a puzzle. Most cases of the congenital form of myotonic dystrophy come from the mother having myotonic dystrophy. This recent information has helped with our understanding of this separate disease.


Lecture on consensus based care for patients with myotonic dystrophy

On May 10th 2019 at the American Academy for Neurology a talk on consensus based care for Myotonic Dystrophy Type 1 will b given at 10am. Dr, Johnson has considerable experience with this disease.

Nicholas E. Johnson, MD, FAAN, is an assistant professor of neurology, pediatrics, and pathology at the University of Utah with a focus in inherited neuromuscular disorders. He received his undergraduate degree in molecular and cellular biology and psychology at the University of Arizona. He then obtained his medical degree at the University of Arizona. He completed his neurology residency and combined fellowship in neuromuscular medicine and experimental therapeutics at the University of Rochester.

His laboratory is focused on identifying the pathogenesis of myotonic dystrophy and facioscapulohumeral muscular dystrophy and identifying appropriate clinical endpoints for these conditions. Johnson conducts therapeutic trials in many other inherited nerve and muscle disorders. He also serves as deputy editor of Neurology® Genetics.

Johnson serves as chair of the Government Relations Committee for the American Academy of Neurology. He is also a member of the American Academy of Neurology’s delegation to the American Medical Association. In these roles, Johnson advocates for improving the practice of neurology for neurologists and their patients.

Here is a link to the information on the talk http://tools.aan.com/annualmeeting/search/index.cfm?fuseaction=home.detail&id=7616&keyword=&81,81,81,81,81,81,81,81,81,81,81,81,81&type=all.

Care Recommendations for families with Congential Myotonic Dystrophy

This is a new consensus based article. It was written by 11 experts in the field of myotonic dystrophy and gives a good basic review of how to approach the families that have congenital myotonic dystrophy.


Bone Problems in children with myotonic dystrophy

Editors Note: Clubfoot is a well know manifestation of congenital myotonic dystrophy. Other orthopedic issues are discussed in this article as well.


Orthopaedic Manifestations of Congenital Myotonic Dystrophy During Childhood and Adolescence

Canavese, Federico MD; Sussman, Michael D. MD

Journal of Pediatric Orthopaedics: March 2009 – Volume 29 – Issue 2 – p 208-213
doi: 10.1097/BPO.0b013e3181982bf6
Selected Topics

Congenital myotonic dystrophy (CMD) is a dominantly inherited disorder manifested in childhood by muscle weakness which can be profound at birth, but which progressively improves over the first few years. Congenital myotonic dystrophy represents the severe end of the spectrum of myotonic dystrophy, which in milder cases may not be diagnosed until adulthood. The goal of the study was to identify and quantitate the musculoskeletal deformities which may significantly affect the function of children with CMD.

Methods: A retrospective chart and radiograph review was performed after Institutional Review Board approval for all cases of myotonic dystrophy from 1987 to 2004 followed at a children‘s specialty orthopaedic hospital. Inclusion criteria were either a conclusive testing for CMD by gene testing, electromyography, and/or muscle biopsy in the child or parent and the presence of a typical clinical picture. Skeletal manifestations were classified by body segment (upper extremity, hand, spine, hip, lower extremity, foot) and by the type of deformity. Surgical procedures and outcomes were also documented.

Results: Thirty children and adolescents met the inclusion criteria. The male/female ratio was 1 (15 boys and 15 girls). In 27 cases, the mother transmitted the disease, and in 2 cases, the father transmitted the disease; in one case, it was impossible to reconstitute the family history of the child who was adopted. The mean age at onset of gait was 29 months. Twenty-two (73%) out of 30 children underwent surgery for lower extremity-, foot-, or spinal-related deformities. The mean follow-up was 11.4 years (range, 3-20 years).

No contractures or deformities were observed in the upper extremities. Spinal deformities affected 9 patients (30%), and 3 of these required surgery. These spinal deformities when present usually had an early onset and included thoracolumbar scoliosis as well as kyphoscoliosis. Problems at the level of the hips and knee were infrequent and included only 2 patients who had unilateral hip abduction contracture and 1 patient who had significant fixed knee flexion contracture. Congenital clubfoot occurred in 5 patients (17%) and generally responded well after posteromedial release and recurrence occurred in only one case. Developmental equinusand equinovarus exclusive of clubfoot affected 7 patients (23%), 70% of whom required surgery. Outcome after Achilles tendon lengthening was positive, and many of the children began walking soon after the Achilles lengthening, and recurrence did not occur.

Conclusions: Child with CMD are at high risk for musculoskeletal deformities of the spine and lower extremities. In our experience, correction and improved function were likely after surgery.

Level of Evidence: Retrospective study; level IV

© 2009 Lippincott Williams & Wilkins, Inc.