Congenital and childhood myotonic dystrophy: Current aspects of disease and future directions

Table 1 Myotonic dystrophy type 1 clinical phenotypes

Phenotype	Clinical characteristics	CTG repeat length	Age of onset (yr)
Premutation	Not applicable	38-49	Not applicable
Mild/late onset adult	Mild myotonia	50-100	20 to 70
	Cataracts
Classical adult	Myotonia	50-1000	10 to 30 (median 20 to 25)
	Muscle weakness
	Cataracts
	Conduction defects
	Insulin resistance
	Respiratory failure
Childhood onset	Facial weakness	> 800	1-10
	Cognitive defects
	Psychosocial issues
	Incontinence
Congenital	Hypotonia	> 1000	Birth
	Respiratory distress
	Cognitive defects
	Motor and developmental delay
	Feeding difficulties

Table 2 Summary of the clinical manifestations in congenital and childhood-onset/juvenile myotonic dystrophy type 1

System	Congenital (CDM)	Childhood-onset/juvenile onset
Prenatal	Polyhydramnios	Not applicable
	Reduced foetal movements
	Preterm delivery
Muscular	Hypotonia at birth	Facial dysmorphia (may be subtle)
	Talipes	Generalised muscle weakness
	Contractures	Myotonia, usually after 1st decade
	Scoliosis, lordosis, kyphosis	Muscle atrophy
	Arthrogryposis	Brisk reflexes
	Characteristic facial dysmorphia	Mild talipes and contractures Motor delay
	Hyporeflexia
	Generalised muscle weakness (distal > proximal)
	Muscle atrophy
	Motor delay
Vision	Visual impairment	Visual impairment
	Strabismus	Strabismus
	Reduced visual acuity	Reduced visual acuity
	Lens pathology	Lens pathology
Respiratory	Respiratory distress at birth	Recurrent infections (weak cough)
	Raised right hemi-diaphragm	Sleep apnoea and sleep disordered breathing
	Pulmonary hypoplasia
	Bronchopulmonary dysplasia
	Aspiration pneumonia
	Sleep apnoea and sleep disordered breathing
	Pneumothorax
	Recurrent infections
	Impaired central respiratory control
Gastrointestinal and feeding	Sucking difficulties from birth	Recurrent abdominal pain
	Gastroparesis
	Gastroesophageal reflux and aspiration
	Constipation
	Recurrent diarrhoea
	Faecal incontinence
	Anal dilatation
	Persistent abdominal pain
CNS	Increased sensitivity to anaesthesia	Hypersomnolence and fatigue
	Neuroendocrine disturbance	Periodic limb movements
	Psychiatric disorders (ADHD, anxiety, depression)	Psychiatric disorders
	Autism	Autism
	Hypersomnolence and fatigue
Cognitive function	Lower IQ	Lower IQ
	Full scale ranges between 40-80	Full scale ranges from 42 to 114
	Mean less than 70	Mean between 70 and 80
Cardiac	Conduction disturbances	Conduction disturbances
	Structural abnormality, valve defects (most commonly mitral)	Structural abnormality, valve defects
		(More common in older patients)
Endocrine	Testicular atrophy	Testicular atrophy
	Hormone abnormalities: growth hormone, hypothyroidism (late teens)	Later onset: hormone abnormalities
Hearing	Recurrent otitis media	Recurrent otitis media (less common)
Oral health	Dental caries, plaque, gingivitis decay/trauma	Dental caries, plaque, gingivitis decay/trauma
Speech and language	Nasal voice and dysarthria	Speech delay
	Speech delay	Nasal voice and dysarthria
Life expectancy	30%-40% death rate within neonatal period	Mortality similar to adult-onset
	Mean life expectancy: 45 yr	Mean life expectancy: approximately 60 yr

CDM: Congenital myotonic dystrophy; ADHD: Attention-deficit/hyperactivity disorder; CNS: Central nervous system; IQ: Intelligence quotient.

Table 3 Sleep disorders in myotonic dystrophy type 1 that contribute to hypersomnolence

Sleep disorder	Description and components
Excessive daytime sleepiness	Greater susceptibility to falling asleep, especially when in situations requiring less attention
	Naps are long, frequent and unrefreshing
Long night time sleep	Sleep often does not feel sufficient or restorative
	Sleep fragmentation and frequent arousals
Sleep related breathing disorders	Sleep apnoea or hypopnoea: Obstructive and/or central
	Hypercapnoea and hypoxemia in both day and night time
RLS and PLM	RLS refers to the urge to move limbs while both awake and asleep, while PLM refers to uncontrolled limb movements during sleep. Both commonly co-exist
REM sleep dysregulation	Abnormal periods of SOREMPs during MSLTs
	Increased density and frequency of REM sleep nocturnally

RLS: Restless leg syndrome; PLM: Periodic limb movements; SOREMPs: Sleep-onset REM periods; MSLTs: Multiple sleep latency tests; REM: Rapid eye movement.

Table 4 Current management strategies in congenital and childhood myotonic dystrophy type 1

Clinical problem	Management strategies
Muscle weakness
General	Exercise and physical therapy
	Possible drug therapy (DHEA, IGF-1, BP3, Creatinine use has shown possible benefits but this is not routinely done)
Talipes, foot drop, osteopenia, contractures	Orthopaedic surgery (e.g., tendon transfer, if required)
	Mobility aids
	Physiotherapy, ankle foot orthoses, splints
(Scoliosis, kyphosis)	Optimise vitamin D and calcium
	Physiotherapy, stretches and splints
Speech (dysarthria)	Orthopaedic surgery
Swallowing/feeding	Speech therapy
	Speech therapy
	Modification of food consistency
	Physiotherapy to enhance swallowing
Myotonia	Occupational therapy – adaptive devices
	Drug therapy (Mexiletine, anti-epileptics, amino acids, antidepressants)
Respiratory
Chest wall weakness and respiratory function	Regular surveillance screening with a symptom checklist including:
	Orthopnoea, dyspnoea with ADLs, sleep disturbances, morning headaches, apnoea, reduced cognition, EDS, fatigue, recent chest infections
	Respiratory function tests including
	Regular forced vital capacity, FEV1, pulse oximetry and peak expiratory cough flow
	Elective monitoring also includes mean inspiratory and
	expiratory pressures, and arterial blood gas analysis
	Imaging may include chest radiography or ultrasound for detection of motion abnormalities and
	thinning of diaphragm
	Nocturnal non-invasive ventilation: BiPAP or CPAP (in more obstructive cases)
Weak cough	CDM: Intubation and ventilation during neonatal period
Greater	Physiotherapy incorporating airway clearing techniques, manual assisted cough and postural drainage of secretions
Susceptibility to infections/recurrent infections	Antibiotics for management of acute infections
	Prophylactic vaccinations
	Respiratory physician consultation
	Prophylactic antibiotics
Cardiac
Conduction disorders	Annual surveillance with ECG and echocardiography
	Holter monitoring
	Pacemaker or defibrillator insertion if indicated
Sleep
Sleep related breathing disorders	Respiratory function testing
	Overnight pulse oximetry
	Polysomnography
	Non-invasive ventilation
Upper airway obstruction/apnoea	Total tonsillectomy or adenoidectomy may be beneficial
Periodic limb movements	Assessment of serum iron and ferritin
	Consider dopaminergic agents
Excessive daytime somnolence	Thorough assessment (questionnaires, actigraphy)
	Drug therapy/psychostimulants (Modafanil)
Hearing	Regular assessment
	Antibiotics for otitis media
	Grommets for recurrent otitis media
Gastrointestinal
Nutrition	Monitoring growth
	Assessment of micronutrients (e.g., iron and vitamin D) and supplementation as needed
	Dietician consultation
Irritable bowel syndrome type symptoms	Antibiotics to counteract bacterial overgrowth
Diarrhoea	Antibiotics (erythromycin)
	Drug therapy (cholestyramine)
Constipation	Stool softeners
	Laxatives/stimulating agents
	Regular toileting routine assisted by bulking agents and laxatives
Faecal incontinence	Cholestyramine
(Anal dilatation)	Colostomy (last resort)
Abdominal Pain	Pain medication (NSAIDs)
	Cholestyramine
Anaesthesia
Hypersensitivity with risk of respiratory depression	Detailed anaesthetic work up and assessment that may include ultrasound examination of gastric volume for risk of aspiration
	Establish airway: modified rapid induction, tracheal tube/supra-glottic device
Increased risk of intraoperative myotonia	Avoid opioid infusions and intravenous administrations
	Consider local anaesthetia as an alternative (Caudal, spinal and epidural)
	Extensive post-operative monitoring and support
	Paracetamol and NSAIDs
Poor oral health	Regular dental hygiene
	Regular visits to general and specialist dental clinics
	Good home care techniques: cleaning, plaque removal
Vision	Early and regular screening
	Prevention of amblyopia
	Early correction of hyperopia and astigmatism
Psychological
Cognitive deficits and mental retardation	Cognitive assessment
	Planning of appropriate education environment and support
Neuropsychiatric comorbidities	Psychotherapy, social skills training
(Attention deficit, personality disorders)	Drug therapy (e.g., stimulants for ADHD)
Social issues	Specialised school or special arrangements

DHEA: Dehydroepiandrosterone; IGF: Insulin-like growth factor; EDS: Excessive daytime sleepiness; BiPAP: Bi-level positive airway pressure; CPAP: Continuous positive airway pressure; CDM: Congenital myotonic dystrophy; NSAIDs: Non-steroidal anti-inflammatory drugs; BP3: Binding protein 3; ADL: Activities of daily living; FEV1: Forced expiratory volume in 1 s; ECG: Electrocardiogram; NSAIDS: Non-steroidal inflammatory drugs; ADHD: Attention deficit hyperactivity disorder.