Dystrophinopathies Clinical Presentation

Updated: Nov 13, 2019
  • Author: Dinesh G Nair, MD, PhD; Chief Editor: Nicholas Lorenzo, MD, CPE, MHCM, FAAPL  more...
  • Print


See the list below:

  • Stage 1 – Presymptomatic

    • Creatine kinase usually elevated

    • Positive family history

  • Stage 2- Early ambulatory

    • Waddling gait, manifesting in children aged 2-6 years; often the first clinical symptom in patients with Duchenne muscular dystrophy and is secondary to hip girdle muscle weakness

    • Inexorable progressive weakness in the proximal musculature, initially in the lower extremities, but later involving the neck flexors, shoulders, and arms

    • Because of proximal lower back and extremity weakness, parents often note that the boy pushes on his knees in order to stand; this is known as Gowers sign (see image below)

      Gowers sign. Gowers sign.
    • Possible toe-walking

    • Can climb stairs

  • Stage 3- Late ambulatory

    • More difficulty walking

    • Around age 8 years, most patients notice difficulty with ascending stairs and respiratory muscle strength begins a slow but steady decline

    • Cannot arise from the floor

    • Approximately the time that independent ambulation is most challenged, the forced vital capacity begins to gradually wane, leading to symptoms of nocturnal hypoxemia such as lethargy and early morning headaches

  • Stage 4 – Early nonambulatory

    • Can self-propel for some time

    • Able to maintain posture

    • Possible development of scoliosis

  • Stage 5 – Late nonambulatory

    • Scoliosis may progress, especially when more wheelchair dependent

    • If wheelchair bound and profoundly weak, patients develop terminal respiratory or cardiac failure, usually by the early 20s, if not sooner; poor nutritional intake can also be a serious complication in individuals with severe end-stage Duchenne muscular dystrophy

    • Contractures may develop [1]

Sometimes a young boy may come to medical attention because of elevated liver function enzymes (AST, ALT), and, in such cases, serum creatine kinase and gamma-glutamyl transferase (GGT) levels should be checked prior to considering liver biopsies.

Occasionally, a young boy may be referred for speech delay or learning issues, but he may harbor a dystrophin mutation. Most children with dystrophinopathy have IQs about 1 standard deviation lower than the general population, but certainly plenty of exceptions exist. The low intellectual skills, such as cognitive issues (learning differences, attention deficit hyperactivity disorder, obsessive-compulsive disorder, pervasive developmental disorder, mental retardation), are seen in up to 30% of patients with dystrophinopathy. Children with Duchenne or Becker muscular dystrophy perform particularly poorly on tests of verbal skills and have challenges in processing complex verbal information. [5]

In some older boys or young men, dilated cardiomyopathy findings may lead to provincial diagnoses such as viral or idiopathic cardiomyopathy when in fact a dystrophin mutation may be the underlying reason. Cardiac surveillance should be implemented at the time of diagnosis and should incorporate echocardiography plus ECG and pediatric cardiology expertise. When dystrophinopathy primarily affects cardiac muscle, the disease is referred to as X-linked dilated cardiomyopathy and patients present at age 20-40 years with congestive heart failure and dilated cardiomyopathy. It is presumed that normal skeletal muscle function in these patients increases the cardiac preload, likely accelerating the development of cardiomyopathy.

Some families and individuals become socially withdrawn, which may further affect their overall psychosocial health. Family, financial, school, community, and sibling issues can be significant.



Generally, neck flexors, wrist extensors, quadriceps, tibialis anterior, biceps, and triceps muscles are affected more than the neck extensors, wrist flexors, deltoids, hamstrings, gastrocnemii, and solei.

Deep tendon reflexes, which tend to parallel muscle fiber loss, slowly diminish and ultimately disappear.

The calf enlargement imparts the illusory appearance of strength, but, in fact, the enlarged calf muscles are caused by fatty and fibrotic infiltration of degenerated muscles. This is seen in conjunction with more prominent toe-walking. Sometimes, an apparent pseudohypertrophy is also seen in the forearms and tongue. However, another explanation may relate to compensatory hypertrophy of the calves secondary to weak tibialis anterior muscles, which tend to be affected earlier and more prominently.

By age 10 years, 70% of children are hobbled by contractures of the iliotibial bands, hip flexors, and heel cords. Most are wheelchair bound by this time, creating a vicious cycle of immobility and further formation of contractures.

Asymmetric weakening of the paraspinal muscles leads to kyphoscoliosis, which in turn further compromises pulmonary and gastrointestinal function.

Inability to generate a forceful cough underlies the development of atelectasis with attendant episodes of pneumonia.

Compared with Duchenne muscular dystrophy, the Becker phenotype manifests slower (ie, in those aged 10-20 y) and evolves over a longer period. Muscle weakness is milder than in Duchenne muscular dystrophy, and calf pseudohypertrophy and contractures are not invariant features.

In contrast to patients with Duchenne muscular dystrophy who are wheelchair bound by age 10 years, some patients with Becker muscular dystrophy are able to ambulate independently past the fourth decade of life; some are able to ambulate into the seventh decade of life.

While average life expectancy of patients with mild Becker muscular dystrophy (ie, ~40s) is diminished compared to that of the general population, survival of these individuals into the seventh or eighth decade of their lives is not unusual.



Duchenne and Becker muscular dystrophy are caused by mutations in the same gene encoding dystrophin. Mutations that result in the absence or severe reduction of the dystrophin protein generally result in Duchenne muscular dystrophy, while those that lead to a less severe reduction and/or expression of an internally truncated, semifunctional protein generally result in Becker muscular dystrophy.

The size of the mutation is not always a determining factor of severity. For example, premature stop codons may be a single DNA base change. There are correlations with the type of mutation, location, and severity. Deletions, duplications, and frame-shift mutations resulting in the absence or truncation of the protein are associated with the most severe phenotypes seen in Duchenne muscular dystrophy, while in-frame mutations generally lead to a less severe phenotype seen in Becker muscular dystrophy. Exceptions or clinical outliers defy these generalizations and researchers believe modifier genes may contribute.

Analysis of the location of deletions has shown that the amino-terminal, cysteine-rich, and carboxy-terminal domains are essential for dystrophin function, while the central rod domain can accommodate large in-frame deletions.

Larger deletions of one or more exons cause approximately 59% of Duchenne muscular dystrophy and 65% of Becker muscular dystrophy cases. Premature stop codon mutations are found in 15%, duplications in 5%, and the rest are caused by frameshift, insertions/deletions, splice site, or missense mutations.

Despite the fact that most of the cases of Duchenne and Becker muscular dystrophy are transmitted in a known X-linked manner (mother may be a known carrier), one third are the result of a spontaneous mutation with no family history.