About Congenital Myotonic Dystrophy

Congenital DM1 (or CDM) is the most severe form of Myotonic Dystrophy Type 1 (DM1), a rare and serious multi-systemic neuromuscular disorder (a form of muscular dystrophy) that affects skeletal and smooth muscle as well as the heart, lungs, eyes, skin, gastrointestinal tract, and endocrine, reproductive, immune and central nervous systems.

Birth
The rarity of Congenital DM1 and its complex and variable presentation at birth makes it challenging to diagnose. Children born with Congenital DM1 can present with life-threatening symptoms including respiratory insufficiency (often requiring ventilator support), low muscle tone ('floppy baby syndrome'), feeding challenges (including the inability to suck and swallow), clubfeet (often requiring surgery and orthotic support), and slow motility of the gastrointestinal system.

Developmental Years
Newborns that survive their critical early challenges often begin to improve, gain strength, and meet many milestones with frequent and intensive, medical, educational, and therapeutic support. They will benefit from ongoing clinical, educational, and familial support throughout their developmental years and beyond.

Although children born with Congenital DM1 deal with severe challenges starting at birth, most parents describe their children as loving, generally happy, funny, smart, brave, and especially resilient.

Congenital DM1 symptoms may include the following:

Cardiac/Heart

1. Conduction (electrical) problems including arrhythmias (bradycardia, ventricular tachycardia, A-fib, A-flutter heart block, etc.), low blood pressure, Raynaud's syndrome, clots/DVTs, heart muscle problems (less common).

Respiratory/Lungs

1. Poor airway clearance, sleep apnea, Co2 retention, hypoventilation, frequent pneumonia, lung collapse, interstitial lung disease.

CNS/Brain

1. Cognitive impacts affecting decision-making and executive function, working memory, focus and attention, problem-solving, follow-through, apathy, organization and emotional regulation and behavior. Extreme fatigue, sleepiness, and autistic-like features or a dual diagnosis of autism. Diminished self- and community-awareness, impacting social interactions. A narrow scope of interest, perseveration, and sensory challenges.

Musculoskeletal

1. Weakness, hypotonia (floppy), muscle wasting/atrophy (arms/legs/shoulders/neck), poor head control, myotonia/contractures, scoliosis, foot abnormalities such as foot drop causing tripping and falling, impaired mobility, muscle pain.

Gastrointestinal

1. Poor/slow motility, constipation and/or diarrhea, poor bowel control/encopresis, gut pain, esophageal myotonia.

Oral Musculature - Speech/Communication

1. Weak oral musculature (mouth and facial muscles), feeding/swallowing issues, choking/aspiration risk, open (tented) lips and poor lip closure, reduced/poor intelligibility, diminished facial expression/affect (easy to misunderstand), increased secretions, abnormally high pallet, teeth problems.

Vision/Eyes

1. Esotropia, hyperopia, amblyopia, strabismus, ptosis, cataracts (more common in adults).

Immune System

1. Low antibodies.

Endocrine and Reproductive System

1. Increased incidence of thyroid, parathyroid, and gonadal dysfunction, including small testes, low sperm count, premature balding, and low testosterone. Abnormal menses (premature, delayed, short (polymenorrhagia), irregular periods). Metabolic-associated liver disease and insulin resistance.

Skin

1. Higher risk of benign skin tumors (pilomatrixomas).

Diagnosis is confirmed though a diagnostic evaluation or genetic test.

There are currently no approved therapies for CDM1 and patients are typically treated with drugs to address different symptoms of the disease. Many patients also receive support through special education and speech and physical therapy.

Our clinical development program in congenital myotonic dystrophy

AMO-02, one of AMO Pharma's lead investigational drugs, is in development for the treatment of congenital myotonic dystrophy, (myotonic dystrophy is the most common form of muscular dystrophy (DM1). It is caused by a mutation in the DMPK gene. Congenital myotonic dystrophy symptoms include muscle weakness and intellectual, sleepiness and developmental impairment.

The safety and efficacy profiles of this therapy and its demonstrated mechanism of action provide strong support for its development in this indication and for potential use in the treatment of certain other orphan and non-orphan diseases.

A phase 2 proof-of-concept study found AMO-02 provided clinical benefit to the majority of subjects after 12 weeks of treatment. Improvements were most evident in cognitive functioning, fatigue and ability to perform activities of daily living, as well as in certain neuromuscular symptoms. In addition, co-occurring autism symptoms improved in several subjects. AMO is now advancing AMO-02 to a Phase 2/3 registration-caliber study in children and adolescents with congenital myotonic dystrophy. The study is intended to commence later this year, conducted at multiple sites across North America and in the UK.

Resources for more information about myotonic dystrophy

There are several organizations available to provide information about myotonic dystrophy and the services available to help families:

Myotonic Dystrophy Foundation
http://www.myotonic.org

Myotonic Dystrophy Support Group
http://www.myotonicdystrophysupportgroup.org

Muscular Dystrophy Association
http://www.mda.org

Muscular Dystrophy Association UK
http://www.musculardystrophyuk.org

Congenital Myotonic Dystrophy
http://congenitalmyotonicdystrophy.org

In addition, many countries now have patient registries for myotonic dystrophy. For additional information on resources and to access a DM family and patient registry, please visit:
https://myotonicregistry.patientcrossroads.org.

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