X-linked dystrophinopathies
Duchenne muscular dystrophy
X recessive myopathy, affecting mostly boys. Rare in heterozygous women; clinical symptoms are milder and with a later onset.
Etiology: The disease associated gene is cloned and mapped on the short arm of the X-chromosome. 60% of cases, there is deletion in the dystrophin gene, in 8% duplication and in the rest there are point mutations. The phenotype expression of type Duchenne or type Becker is dependent on the mutation type.
Pathogenesis: The DMD gene is responsible for the production of the protein dystrophin, an important part of the muscle fibre cell membrane. The gene mutations result in almost complete absence of dystrophin.
Clinical picture:
- Usually the disease onset is before the age of 5. Some children start to walk late and have clumsy gait before the disease onset.
- Complain of frequent falls, difficulties climbing stairs, difficulties in standing up from a squat position. Progressive muscle weakness predominantly affecting in the proximal muscles of the lower limbs.
- A frequent symptom is the pseudo-hypertrophy of the calves. Cognitive disturbances, cardiac and nanism. The patients lose independent gait before the age of 13. Later on skeletal deformities develop, which lead to reduced respiratory capacity, recurring pneumonia and respiratory failure.
Examination:
- Creatine kinase levels increased 10 times above the norm, corresponds to the age and state of the patient.
- EMG shows generalised myopathic pattern
- ECG and echocardiography is needed for assessing the cardiac status
- Histological examination reveals atrophic and hypertrophic changes, necrotic and regenerated fibres, hyalinated fibres, increased endomysial connective and adipose tissue.
- Immunohistochemical examination shows lack of dystrophin.
- Molecular genetic analysis detects various mutations in the dystrophin gene on Xp21.
Diagnosis;
- Typical clinical picture
- X-recessive trait of inheritance
- Myopathic changes on EMG
- Elevated creatine kinase
- Results from the immunohistochemical and molecular genetic tests
Treatment: Prednisolone or deflazacort treatment is recommended. It is considered that this treatment extends the duration of walking, though side effects such as weight gain, reduced bone density, mood swings. Kinesitherapy is an important element.
Prognosis is grave. Most patient die before 25 due to cardiac and respiratory complications.