Diagnosis, treatment and follow-up of patients with Duchenne muscular dystrophy

Key points

• Duchenne muscular dystrophy (DMD) is an X-linked recessive disease affecting one in every 3800-6300 male live births and is the most frequent muscular dystrophy in children.
• In suspected DMD, serum creatine kinase (CK) is measured. A genetic study (MLPA first, then sequencing) is recommended because it may avoid a muscle biopsy.
• Corticosteroids (prednisone 0.75 mg/kg/day or deflazacort 0.9 mg/kg/day) are started when motor function reaches a stable level (4-6 years of age). Continuing them after loss of ambulation has shown benefits.
• Ataluren targets nonsense mutations (10% of cases), and eteplirsen skips exon 51.
• Care should be multidisciplinary, with regular musculoskeletal, respiratory, cardiac, nutritional and cognitive follow-up.

Overview

This consensus statement was written by a Spanish working group of neurologists, paediatric neurologists and rehabilitation specialists. It sets out how to diagnose, treat and follow up patients with DMD. The authors grade evidence with American Academy of Neurology criteria. Management should be multidisciplinary and adapted to the patient and stage of disease: corticosteroids plus gastrointestinal, respiratory, cardiac, orthopaedic and physiotherapy measures, with genetic studies playing a key role.

Disease course

Most patients are diagnosed between 3 and 5 years of age. Early signs include difficulty walking, frequent falls, difficulty climbing stairs, toe-walking and a positive Gowers sign. Motor development plateaus between 4 and 8 years and then declines. Most patients lose the ability to walk at 12-14 years, and scoliosis affects 90%. Approximately 20%-34% have intellectual disability, autism spectrum symptoms or other cognitive or behavioural alterations. Corticosteroids and better management of complications have extended survival to the third or fourth decade.

Diagnosis

CK levels in DMD are 10-100 times higher than normal. A parallel rise in transaminases may lead to an erroneous suspicion of liver disease. Deletions (approximately 60%-65%) and duplications (5%-15%) are detected by MLPA. If MLPA is negative, sequencing looks for point mutations or small deletions or duplications. A muscle biopsy is needed if no mutation is found but CK is high and the clinical picture fits. If a biopsy is done first, genetic testing should follow.

Corticosteroids and targeted drugs

Before steroids, the vaccination programme should be completed and immunity to varicella demonstrated. Prednisone may also be given on alternate days or 10 days on and 10 days off. Continuous deflazacort appears generally safer. If adverse effects are not easily manageable, the dose is reduced by 30% before withdrawal is considered. Ataluren received conditional EMA authorisation in July 2014 for ambulant patients older than 5 years with a nonsense mutation. Eteplirsen applies to some deletions (13% of cases) and was approved by the FDA.

Organ-specific follow-up

Twice-yearly musculoskeletal assessments are advised. Night-time ankle-foot orthoses are appropriate in all phases. Swimming is recommended, but high-intensity and eccentric exercise should be avoided. Forced vital capacity (FVC) is checked annually while walking and every 6 months after loss of ambulation, with sleep studies when FVC is below 60%. Electrocardiography and echocardiography are done at diagnosis, twice yearly until age 10 and annually thereafter. ACE inhibitors are first-line and are supported before signs of ventricular dysfunction appear. Intravenous anaesthetics are recommended, and depolarizing muscle relaxants are contraindicated. One-third of mothers of affected children are not carriers.

Frequently asked questions

When should corticosteroids be started?

When the child's motor function reaches a stable level, at 4-6 years of age, after completing vaccinations and confirming varicella immunity.

Is a muscle biopsy always needed?

No. A genetic study may avoid it; biopsy is used when no mutation is found but CK is high and symptoms are compatible.

Why are inhalation anaesthetics avoided?

Agents such as halothane or isoflurane carry a high risk of malignant hyperthermia and rhabdomyolysis in DMD.

Source

Nascimento Osorio A, Medina Cantillo J, Camacho Salas A, Madruga Garrido M, Vilchez Padilla JJ. Consensus on the diagnosis, treatment and follow-up of patients with Duchenne muscular dystrophy. Neurología (English Edition) 2019;34(7):469-481. DOI: 10.1016/j.nrleng.2018.01.001 (Spanish original DOI: 10.1016/j.nrl.2018.01.001). Open access. Funded by an independent research grant from PTC Therapeutics. This page is a summary prepared by Medpresso from the original publication and is not a substitute for the full text or for medical advice.