Dystrophinopathies
Dystrophin found in skeletal, cardiac and smooth muscle, as well as CNS tissue (static encephalopathy)
Duchennes
Genetics
HPC
Prognosis
Beckwith
Dx
Rx
Issues
Supports
Ex
Duchennes
Genetics
- X-Linked recessive (2/3 de novo)
HPC
- GM delay / regression, proximal weakness, waddling gait, difficulty with stairs, continue to gain skills until 6yo, wheel chair by 12y untreated
- Respiratory impairment
- Dilated cardiomyopathy
Prognosis
- life expectancy 30s
Beckwith
- presents later with more severe cardiomyopathy ? due to better skeletal exercise tolerance
Dx
- Muscle panel
- CGH array
- Next gen sequencing
- Muscle Biopsy
Rx
- Steroids usually started at the point of plateau of motor milestone gains. but trend towards starting earlier
- prednisolone 0.75mg/kg/day
- immunosuppressive, myogenic, reduced apoptosis
- SE: weight gain, reduced linear growth, pubertal delay, Cushingoid features, hypertension, osteoporosis with consequent long bone and vertebral compression fractures, hyperglycaemia, easy bruising and usually transient behavioural problems
Issues
- Genetics
- Prenatal testing available via CVS / Amniocentesis
- Family genetic counselling
- Carrier females can be affected
- Respiratory / sleep: Physio, cough assist (neg pressure exsufflation), NIV, monitor PFTs
- Respiratory failure: 6/12 PFTs (FVC = diaphragmatic strength, PIP/PEP = chestwall/ abdominal muscle strength)
- FVC <50%, CO2 >45, O2 <88 for 5mins > NIV (untreated hypercapnia fatal within 1 year)
- Initially at night, then 24 hours
- Once 24 hours, consider tracheostomy to prevent pressure injury from straps
- Reduces LRTI
- Sleep hypoventilation, REM hypoxia, OSA
- LRTI: bronchodilators, ABs, Mycolytics,
- Hypoxia > inc Pulmonary vascular resistance > Cor pulmonale (RHF)
- Avoid smoke
- Immunisation including pneumococcal/fluvax
- Respiratory failure: 6/12 PFTs (FVC = diaphragmatic strength, PIP/PEP = chestwall/ abdominal muscle strength)
- Cardiac (with introduction of steroids and NIV, is now the life limiting complication)
- myopathy > ECG/ECHO q2y until 10 then annually
- Rx Ejection fraction <55% /dilation with ACEi (perindopril) or AT2RB (losartan) or beta blocker (metoprolol)
- in failure digoxin / diuretics
- Heart transplant
- arrhythmia: ectopics or sinus tachycardia ECG/Holter
- Cor pulmonale
- (NB CARRIERS CAN DEVELOP CARDIAC DISEASE WITHOUT WEAKNESS)
- myopathy > ECG/ECHO q2y until 10 then annually
- GIT
- Dentition (OT for brushing appliance)
- Dysphagia: Barium ?gastrostomy
- GOR/vomiting
- Conspitation, incontinence
- Incontinence due to ?Myopathic bladder
- ?Oxybutinin to reduce contractions
- Scoliosis
- 12monthly if cobb <15
- 6monthly if cobb >15
- Contractures
- Prevention
- Stretching (Physio)
- Serial casting / AFO (OT/orthoptist)
- Wrist splints (OT/orthoptist)
- Treatment
- Surgery: balance risk of anaesthetic/immobility with gain of ROM when weakness rather than contracture usually the limiting factor with mobility
- Prevention
- Bone health (immobility / steroids)
- Annual: CMP, ALP, 25-hydroxyvitamin D, PTH, Urine (calcium for hypercalciuria; sodium; creatinine)
- 30mins standing wt bearing if able
- ADLS > Allied health
- Mobility
- Manual wheel chair from ~9yo
- Powereds from ~11yo
- Home mods (no steps, wide doors)
- Mobility
- Behaviour ASD / ADHD more common
- Depression / anxiety
- Complications of Steroid side-effects / sick day stress cover
- Pubertal delay
- LH, FSH, Testosterone
- Rx Testosterone in consultation with an endocrinologist
- improves bone density, linear growth, and psychology
- Pubertal delay
- Medic alert
- Steroids (Immunosuppression/Adrenal suppression)
- Risk of malignant hypertension (muscle contraction/rhabdo/hyperK/fever) like reaction with anaesthetics
Supports
- DMD Family Support Group provided by the Muscular Dystrophy Association
- SW / psychologist with diagnosis / deterioration to deal with grief reaction
Ex
- Mood, intelligence, communication
- Reduced muscle bulk
- Lumbar lordosis
- Scoliosis
- Internal rotation of hips
- Pseudohypertrophy calves (thigh wasting)
- Reduced power, reflexes intact sensation
- Knee-locking (early locking of knee) gait for stability
- Waddling trendelenberg gait
- Using Gowers manoeuvre
- Tachycardia (early), failure (late)
- ASD / ADHD