Tag Archives: Duchenne muscular dystrophy

What is the true C£$T of a rare disease?

A very interesting study from Kate Bushby and colleagues

DMD study

While rare genetic diseases are by definition individually uncommon, they represent a enormous global health burden.

In the European Union alone an estimated 30 million people are affected by a rare disease with a prevalence of less than 1 in 2,000. Rare connective tissue diseases have an overall prevalence estimated at 1/2,000, while musculoskeletal disease in general have an overall prevalence of 1/130 newborns, reflecting their great diversity.

Many inherited connective tissue diseases are congenital, chronic, life threatening and associated with substantial morbidity, extensive and expensive heath care needs and considerable physiological stress and financial burden for affected families.

While the cost burden of rare connective tissue diseases in terms of illness and economic load is not known this recent study of Duchenne Muscular Dystrophy, with a prevalence of ~1 in 5,000, reported that the mean per-patient annual direct cost of illness was estimated at between 7 to 16 times higher than the mean per-capita health expenditure. Moreover, the indirect and informal costs, along with total societal and household burden, was even higher and increased substantially with disease progression.

Download the open access paper here.

Double trouble: myopathy and dysplasia


‘Double trouble’: Diagnostic challenges in Duchenne muscular dystrophy in patients with an additional hereditary skeletal dysplasia.

An interesting paper recently published by Carsten Bonnemann’s Group @NIH:-

Three unrelated young boys presented with skeletal dysplasia, in whom an additional diagnosis of Duchenne muscular dystrophy (DMD) was later established.

  • Two of the boys had Osteogenesis Imperfecta (OI) caused by COL1A1 mutations and were later found to have mutations in the dystrophin gene (at 3 and 15 years respectively).
  • The third boy had pseudoachondroplasia caused by a COMP mutation and also found to have a dystrophin mutation at age 9.

The authors conclude that:-

“Additional series of patients with DMD and a secondary inherited condition are necessary to establish the natural history in this “double trouble” population. The recognition and accurate diagnosis of patients with two independent genetic disease processes is essential for management, prognosis, genetic risk assessment, and discussion regarding potential therapeutic interventions.”


But, what are chances of having two rare diseases like this?

DMD affects 1 in 4000-6000 live births; PSACH and OI both have a prevalence of ~1 in 15,000-20,000.

A back of an envelope calculation suggests a chance of 1 in 100 million for two de novo mutations !

Never-the-less, these ultra rare ‘digenic events’ do happen and will influence disease presentation and severity.

Note that in all three cases (not unsurprisingly) the skeletal manifestations preceded that  of the myopathy.


Finally, the authors also comment that skeletal anomalies ‘mask’ the presentation of muscle weakness and thereby delaying a diagnosis. We would agree with this and also add that muscle weakness in pseudoachondroplasia and multiple epiphyseal dysplasia is often ‘passed off’ as of no consequence, whereas it has a pathological cause and represents a true co-morbidity.

See here.