Ophthalmology – Myotonic Dystrophy

Basics

Description

Myotonic dystrophy is an inherited multisystem disorder characterized by:

• Myotonia
• Progressive muscle weakness
• Cataract formation
• Cardiac conduction disease
• Respiratory dysfunction
• Endocrine abnormalities
• Gastrointestinal dysmotility
• Variable cognitive and behavioral manifestations

It is the most common muscular dystrophy of adulthood.

Two major forms are recognized:

Type 1 – DM1

Also called Steinert disease.

Features include:

• Approximately 98% of classic cases
• Onset from childhood to adulthood
• Distal and facial weakness are common
• Can occur in a severe congenital form
• More prominent multisystem involvement

Type 2 – DM2

Also called proximal myotonic myopathy.

Features include:

• Usually milder than DM1
• Typically adult onset
• More proximal muscle weakness
• Muscle pain is relatively common
• Congenital form is not typical

Epidemiology

Myotonic dystrophy affects men and women equally.

Typical age ranges include:

• DM1: childhood to approximately 40 years
• DM2: approximately 20–60 years

Prevalence varies considerably by population and geographic region.

A commonly cited overall prevalence is approximately:

1 in 8,000

although modern estimates vary.

Genetics

Myotonic dystrophy is inherited in an:

Autosomal dominant pattern

Both forms are caused by unstable nucleotide-repeat expansions.

DM1 Genetics

DM1 results from expansion of a:

CTG trinucleotide repeat

in the:

DMPK gene on chromosome 19

The number of repeats often increases between generations.

DM2 Genetics

DM2 results from expansion of a:

CCTG tetranucleotide repeat

in the:

CNBP gene on chromosome 3

This gene was historically called ZNF9.

Anticipation

Myotonic dystrophy demonstrates anticipation, particularly DM1.

This means:

• Symptoms may appear earlier in successive generations
• Disease severity may increase
• Repeat expansion tends to enlarge during transmission

Severe congenital DM1 is particularly associated with maternal transmission.

General Prevention

The disease itself cannot currently be prevented, but reproductive counseling may include:

• Genetic counseling
• Prenatal diagnosis
• Preimplantation genetic testing

Pathophysiology

The expanded nucleotide repeats are transcribed into abnormal RNA.

These abnormal RNA molecules:

• Accumulate within the nucleus
• Bind RNA-splicing proteins
• Disrupt normal messenger RNA processing
• Cause widespread abnormalities in multiple tissues

Important affected pathways include:

• Skeletal muscle chloride channels
• Insulin receptors
• Cardiac conduction proteins
• Troponin pathways

This explains the multisystem nature of the disorder.

Mechanism of Myotonia

Abnormal splicing of skeletal muscle chloride-channel RNA reduces normal chloride conductance.

This produces:

Delayed muscle relaxation after contraction

which is the hallmark of myotonia.

Ophthalmic Features

The most important ocular abnormalities include:

• Cataract
• Ptosis
• Orbicularis weakness
• Delayed eyelid opening after forceful closure
• Slow saccades
• Progressive external ophthalmoplegia
• Low intraocular pressure
• Pigmentary retinal abnormalities

Cataract

Cataract is the most common ocular manifestation.

The classic early finding is the:

Christmas tree cataract

characterized by:

• Multicolored
• Iridescent
• Crystalline
• Polychromatic lens opacities

They may appear:

• Red
• Green
• Blue
• Gold

under slit-lamp illumination.

Later Cataract Changes

As disease progresses, patients may develop:

• Stellate posterior cortical cataract
• Posterior subcapsular opacity
• More generalized visually significant cataract

Cataract may eventually become a major cause of visual impairment.

Eyelid Findings

Ptosis

Ptosis occurs because of weakness of:

• Levator palpebrae
• Facial musculature

Ptosis may be bilateral and progressive.

Orbicularis Weakness

Orbicularis oculi weakness may cause:

• Incomplete forceful eyelid closure
• Exposure symptoms
• Reduced blink strength

Eyelid Myotonia

After forceful eyelid closure, patients may have:

Delayed reopening of the eyes

because of myotonia of the orbicularis muscle.

Ocular Motility

Patients may develop:

• Slow saccades
• Mild external ophthalmoplegia
• Reduced ductions

Despite motility abnormalities:

Diplopia is often surprisingly uncommon

because weakness progresses slowly and is frequently symmetric.

Intraocular Pressure

Low intraocular pressure has been reported.

This generally does not cause symptoms but may reflect reduced ciliary body or ocular muscle function.

Retinal Findings

A pigmentary retinopathy may occur.

Possible findings include:

• RPE mottling
• Peripheral pigmentary change
• Retinal degeneration resembling mitochondrial retinopathy in some cases

The retinal findings are usually less clinically important than cataract and systemic disease.

History

Important symptoms include:

• Delayed relaxation after gripping
• Difficulty releasing a handshake
• Muscle stiffness
• Progressive muscle weakness
• Dysphagia
• Dysarthria
• Muscle pain, particularly in DM2
• Daytime somnolence
• Disturbed sleep
• Hypoventilation
• Constipation
• Abdominal discomfort
• Urinary or fecal incontinence
• Infertility
• Palpitations
• Syncope
• Blackouts
• Cognitive or behavioral changes

Women may also have:

• Pregnancy complications
• Difficult labor
• Increased obstetric risk

Physical Examination

Characteristic findings include:

• Myotonia
• Facial muscle weakness
• Temporal wasting
• Masseter wasting
• Frontal balding
• Long, thin facial appearance
• Slack mouth
• Neck flexor weakness
• Limb-muscle wasting

The characteristic facial appearance has historically been described as a:

“Hatchet face.”

Handshake Myotonia

When the patient grips the examiner’s hand firmly, they may have difficulty releasing it promptly.

This is a classic demonstration of:

Grip myotonia

Percussion Myotonia

Tapping certain muscles may cause:

• Sustained contraction
• Delayed relaxation

This can be demonstrated over muscles such as:

• Thenar eminence
• Tongue

Bulbar and Speech Findings

Patients may develop:

• Nasal speech
• Monotonous voice
• Dysarthria
• Dysphagia

Bulbar dysfunction increases aspiration risk.

Respiratory Findings

Respiratory involvement may include:

• Hypoventilation
• Sleep-disordered breathing
• Respiratory muscle weakness
• Excessive daytime sleepiness

Respiratory complications are an important cause of morbidity.

Cardiac Findings

Cardiac manifestations are particularly important because they can cause sudden death.

Possible abnormalities include:

• Sinus bradycardia
• AV block
• Bundle branch block
• Atrial arrhythmias
• Ventricular arrhythmias
• Cardiomyopathy

Patients may report:

• Palpitations
• Syncope
• Presyncope

Endocrine Findings

Possible endocrine abnormalities include:

• Insulin resistance
• Diabetes mellitus
• Testicular atrophy
• Infertility
• Thyroid dysfunction

Gastrointestinal Findings

Patients may experience:

• Dysphagia
• Constipation
• Abdominal pain
• Gastrointestinal dysmotility

Diagnostic Testing

Molecular Genetic Testing

The gold standard is molecular confirmation of the repeat expansion.

Testing includes:

• DMPK CTG expansion testing for DM1
• CNBP CCTG expansion testing for DM2

This usually confirms the diagnosis without the need for muscle biopsy.

Electromyography

EMG may demonstrate:

Myotonic discharges

often described acoustically as a waxing-and-waning “dive-bomber” pattern.

EMG can support the diagnosis when the phenotype is uncertain.

Laboratory Testing

Possible abnormalities include:

• Mildly elevated creatine kinase
• Insulin resistance
• Glucose intolerance

Immunoglobulin studies may occasionally show:

• Reduced IgG
• Reduced IgM

These findings are not diagnostic.

Brain MRI

MRI may demonstrate:

• Bilateral white-matter hyperintensities
• Frontal predominance
• Temporal or insular predominance

These abnormalities are more relevant in patients with cognitive or neurologic symptoms.

Slit-Lamp Examination

Slit-lamp examination is important because the characteristic:

Christmas tree cataract

may be highly suggestive of myotonic dystrophy, particularly in a young adult.

Electrocardiography

ECG may show:

• Prolonged PR interval
• Widened QRS complex
• AV conduction delay
• Intraventricular conduction abnormalities

Because conduction disease may be asymptomatic, regular cardiac surveillance is essential.

Additional Cardiac Testing

Depending on symptoms and disease severity, monitoring may include:

• Holter monitoring
• Event monitor
• Echocardiography
• Electrophysiologic studies

Pulmonary Testing

Assessment may include:

• Forced vital capacity
• Sleep study
• Overnight oximetry
• Blood gas testing in selected patients

These help detect respiratory muscle weakness and nocturnal hypoventilation.

Swallowing Assessment

Formal swallowing evaluation may be needed in patients with:

• Choking
• Aspiration
• Recurrent chest infections
• Dysphagia

Muscle Biopsy

Muscle biopsy is rarely needed now because genetic testing is definitive.

Histologic findings may include:

• Central nuclei
• Fiber-size variability
• Disruption of myofibrils
• Sarcoplasmic abnormalities
• Mitochondrial changes

Differential Diagnosis

Important differential diagnoses include:

• Other muscular dystrophies
• Other myotonic disorders
• Myotonia congenita
• Paramyotonia congenita
• Mitochondrial disease
• Chronic progressive external ophthalmoplegia
• Polymyositis
• Stiff-person syndrome
• Mild tetanus

Treatment

There is currently no curative treatment that reverses the genetic defect.

Management is:

• Multidisciplinary
• Preventive
• Supportive
• Directed at organ-specific complications

Muscle Weakness

Management may include:

• Regular low-to-moderate intensity exercise
• Physical therapy
• Occupational therapy
• Ankle-foot orthoses for foot drop

Excessive fatigue should be avoided.

Myotonia

Myotonia does not always require treatment.

When clinically troublesome, selected medications may be used by neurology.

Treatment depends on:

• Functional limitation
• Cardiac status
• Drug tolerance

Daytime Sleepiness

Management may include:

• Evaluation for sleep-disordered breathing
• Noninvasive ventilation
• CPAP or BiPAP when indicated
• Wake-promoting medications in selected patients

Modafinil may be considered in selected individuals.

Respiratory Support

Patients with nocturnal hypoventilation may benefit from:

• Noninvasive positive-pressure ventilation
• BiPAP

Respiratory status should be monitored longitudinally.

Cardiac Treatment

Conduction disease may require:

• Pacemaker
• Implantable cardioverter-defibrillator in selected patients

Cardiology follow-up is essential.

Cataract Surgery

Visually significant cataracts can be treated with:

Cataract extraction and intraocular lens implantation

Visual prognosis is generally good if there is no significant retinal or optic nerve disease.

Ptosis Surgery

Ptosis repair may be considered when ptosis:

• Obstructs the visual axis
• Causes significant functional impairment

However, surgery should be performed cautiously because:

• Orbicularis weakness may impair eyelid closure
• Overcorrection can cause lagophthalmos
• Exposure keratopathy may result

Ophthalmic Follow-Up

Regular ophthalmic examinations should monitor for:

• Cataract progression
• Visual acuity changes
• Ptosis
• Exposure keratopathy
• Ocular motility abnormalities
• Retinal changes

Multidisciplinary Follow-Up

Patients may require ongoing care from:

• Ophthalmology
• Neurology
• Cardiology
• Pulmonology
• Physical therapy
• Endocrinology
• Gastroenterology
• Genetics
• Sleep medicine

Genetic Counseling

Genetic counseling is important because inheritance is:

Autosomal dominant

Each affected individual generally has a 50% chance of transmitting the mutation to each child.

Anticipation should be discussed, particularly in DM1.

Anesthesia Considerations

Patients with myotonic dystrophy have an increased risk of complications during general anesthesia.

Potential problems include:

• Respiratory depression
• Aspiration
• Cardiac arrhythmias
• Prolonged ventilatory failure
• Abnormal sensitivity to sedatives and neuromuscular medications

The anesthesia team should always be informed of the diagnosis before surgery.

Prognosis

DM1

DM1 may significantly reduce life expectancy, particularly when there is:

• Severe cardiac disease
• Respiratory failure
• Congenital disease

DM2

DM2 is generally milder, and life expectancy is often near normal.

Complications

Major complications include:

• Cataract
• Ptosis
• Exposure keratopathy
• Progressive muscle weakness
• Respiratory insufficiency
• Aspiration
• Sleep-disordered breathing
• Cardiac conduction block
• Arrhythmia
• Sudden cardiac death
• Diabetes and insulin resistance
• Infertility
• Gastrointestinal dysmotility
• Increased perioperative and anesthesia risk

Ophthalmology Pearls

• Christmas tree cataract is the classic ocular finding of myotonic dystrophy.
• It consists of multicolored, iridescent crystalline lens opacities.
• Bilateral early cataract in a young adult should prompt consideration of a systemic neuromuscular disorder.
• Delayed eyelid opening after forceful closure is due to orbicularis myotonia.
• Ptosis results from progressive levator weakness.
• Ocular motility may be reduced, but diplopia is often uncommon because the ophthalmoplegia is slow and relatively symmetric.
• Ptosis surgery requires caution because orbicularis weakness can lead to exposure keratopathy.
• The most dangerous systemic manifestations are cardiac conduction abnormalities and respiratory failure.
• Genetic testing for DMPK in DM1 or CNBP in DM2 confirms the diagnosis.
• Any patient undergoing ocular surgery requires careful preoperative assessment because myotonic dystrophy carries a significant anesthetic and cardiopulmonary risk.