Introduction

Myotonic dystrophy is a genetic, multisystem disorder characterized by a debilitating loss of muscle mass and affecting skeletal and smooth muscles, the heart, brain, eyes, and other organs.^1,2

Types of myotonic dystrophy (DM1 and DM2)

Based on their clinical and molecular characteristics, two distinct subtypes of myotonic dystrophy (DM) have been identified.

The two known subtypes of myotonic dystrophy, type 1 (DM1), also known as Steinert disease, and type 2 (DM2), are both autosomal dormant and are caused by unstable repeat expansions of (CTG)n in the dystrophia myotonica protein kinase (DMPK) gene and (CCTG)n in the zinc finger protein 9 (ZNF9) gene, respectively.³

DM is characterised by marked variability in clinical presentation and disease progression both within families and between different families, highlighting the complex nature of this genetic disorder.³ These expansions occurring in the noncoding regions of the gene lead to the production of toxic RNA, which disrupts normal cellular function. With each successive generation, these repeated expansions increase in size, leading to an earlier onset and greater severity of the disease.⁴

DM can be clinically classified based on age of onset into congenital, infantile/juvenile, adult-onset, and late-onset forms.⁵

Prevalence and significance of the condition in children

DM type 1 usually affects children from birth, whereas DM type 2 typically affects adults. The actual global prevalence is unclear; however, children with CDM account for 10%-30% of the total DM1 population.⁶
The prevalence of DM1 is relatively high, with about 4.76 cases per 10,000 births, which equates to approximately 1 in every 2,100 births.⁷ Mortality during the neonatal period can be as high as 40%.⁸

Those with 150 to 1,000 repeats typically have a young adult onset, while individuals with over 1,000 repeats face a more severe course, often beginning in childhood or infancy. Premutation carriers, with 35 to 49 repeats, risk expansion in future generations, particularly when passed from mother to child.⁷ 

Types of myotonic dystrophy in children

Congenital myotonic dystrophy (CMD)

Age of onset

It typically affects infants from birth.

Description and specific characteristics

Congenital myotonic dystrophy (CDM) is the most severe form of DM1.⁹ CDM is a rare neuromuscular and also neurodevelopmental disorder marked by significant hypotonia and muscle weakness at birth, with symptoms generally improving as the individual ages.¹⁰

Infants with Congenital DM1 exhibit significant brain structure abnormalities from birth.¹¹ A characteristic feature observed in patients with Congenital DM1 is the "fish-shaped" upper lip, characterized by an inverted V-shaped appearance resulting from significant facial weakness. This condition leads to a weak cry and challenges with sucking.¹²

In Congenital Myotonic Dystrophy (CDM), children typically exhibit a range of neurobehavioral characteristics, including lower IQ, challenges in adaptive skills and executive functioning, poor sleep quality, and symptoms resembling autism with altered social functioning.¹³

Childhood and juvenile myotonic dystrophy

Age of onset

The childhood form of DM1 typically begins between ages one and ten, while the juvenile form begins between ages 11 and 20.¹⁴ 

Description and specific characteristics

In cases of childhood DM, there are often specific cognitive deficits that primarily affect working memory, attention, and visuospatial functions.¹⁵ Personality changes and behavioural problems have been predominantly observed in juveniles.¹⁶

Symptoms and clinical manifestations

Symptoms at presentation vary, and the size of repeat expansions does not always correlate directly with the severity of symptoms.¹⁷

 Congenital myotonic dystrophy

• Hypotonia
• Respiratory problems 
• Gastrointestinal and feeding difficulties
• Facial weakness is common in both CDM and juvenile DM patients. These patients often exhibit impaired facial expressions, with some having their mouths partially open, while a few have their tongues stuck between their teeth¹⁸
• Developmental delays
• Arthrogryposis (congenital joint contractures) affecting the ankles results in clubfoot. 
• Cognitive impairment

Childhood and juvenile myotonic dystrophy

The symptoms associated with this condition may include;¹⁹

• Muscle weakness and wasting
• Myotonia
• Cardiac issues
• Endocrine abnormalities
• Children and adolescents diagnosed with DM1 exhibit a variety of visual function abnormalities, including hyperopia and astigmatism²⁰

Diagnosis

When doctors physically examine patients with DM1, the distinctive physical traits, combined with additional diagnostic tests, help make the diagnosis more straightforward.

Detailed patient history

DM1 diagnosis should be considered in children with a family history of the disease or symptoms such as oral motor weakness, distal muscle weakness in fingers and wrists without joint stiffness, neck muscle weakness, myotonia (muscle stiffness), autistic traits or social communication difficulties, attention deficit disorder, anxiety, and other behavioural issues. These signs indicate potential DM1 and require further evaluation for diagnosis.⁶

Physical examination

The respiratory rate and heart rate, as well as the head circumference, weight, and height of the patients, are measured. A thorough examination is done to check for scoliosis, dysmorphic features, and contractures. The cardiac and pulmonary systems are evaluated for abnormal chest rises and murmurs, while abdominal exams are for organomegaly.⁸

Genetic testing

Identification of the DMPK gene mutation (DM1)

DM1 is diagnosed by identifying a specific genetic mutation associated with the disease. This involves detecting an expansion of the CTG triplet repeat in the 3' untranslated region of the DMPK gene, located on the long arm of chromosome 19 (19q13.3).

Detection of the CTG expansion is performed using a 10 ml blood sample in EDTA. 

Polymerase chain reaction (PCR) can detect expansions of up to 180 CTG repeats, while southern blot analysis identifies CTG repeats above 180.²¹

Other tests done are:

1. Electromyography is an electrodiagnostic test that is a vital screening tool for identifying myotonic dystrophy type 1 (DM1) and assesses muscle electrical activity
2. Muscle biopsy
3. Brain MRI

Management and treatment

Multidisciplinary approach

A multidisciplinary team approach is essential for providing comprehensive care to manage symptoms, prevent complications, optimise function, and conduct health monitoring. This team typically includes genetic counsellors, nurses, educators, physiotherapists, speech therapists, occupational therapists, social workers, dietitians, and various medical specialists.²²

Management 

1. Physiotherapy
2. Occupational therapy
3. Strength training, aerobic exercise programs, or a combination of both can help optimise muscle and cardiorespiratory function while preventing additional disuse atrophy and deconditioning²³
4. The use of ankle-foot orthoses, wheelchairs, or other assistive devices
5. Medications. There is no known cure for DM, but drugs are used to manage symptoms and improve patient quality of life. An example of a drug is methylphenidate, a stimulant that can be used in children aged 5 and older, as well as teenagers, to improve symptoms of Attention Deficit Hyperactivity Disorder (ADHD)

Genetic counselling

DM1 is inherited in an autosomal dominant manner, with the offspring of affected individuals having a 50% chance of inheriting the expanded allele. The lengthening of pathogenic alleles during gametogenesis can lead to earlier onset and more severe symptoms in subsequent generations. Prenatal and preimplantation genetic testing are available options once DM1 has been confirmed through molecular genetic testing in affected family members.²⁴

Research and future directions

The pathophysiology of DM has spurred the development of early therapeutic strategies, with efforts focused on targeting the toxic RNA (CUGexp/CCUGexp) structure. This involves preventing its formation, promoting its degradation, or blocking it using various molecules and technologies. Despite these efforts, an effective treatment for DM patients remains elusive, with only a few drugs showing limited success in various stages of clinical trials.²⁵

Summary 

Myotonic dystrophy (DM) is a genetic, multisystem disorder characterised by a debilitating loss of muscle mass and affecting skeletal and smooth muscles, the heart, brain, eyes, and other organs. 

There are two types of myotonic dystrophy: myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2). DM1 affects children, while DM2 is more common among adults DM type 1 can affect children at any age from birth (congenital DM) and can develop during childhood. DM is caused by mutations in the genes involved in the structure and functioning of the muscle, resulting in muscle weakness and wasting.

Symptoms vary among individuals. Hypotonia, myotonia, facial weakness, cognitive impairments, respiratory problems, and gastrointestinal and feeding difficulties are symptoms associated with the condition in children.

Doctors experienced in neuromuscular disorders can often diagnose type 1 myotonic dystrophy (DM1) easily. By observing a person's appearance, taking a patient history, and conducting an examination, they can quickly suspect DM1. DM1 is diagnosed by identifying a specific genetic mutation associated with the disease.

Management of DM1 requires a comprehensive approach to care, involving a multidisciplinary team working together to address symptoms, prevent complications, enhance function, and monitor health effectively.