Dear Editor,
I read with interest the article by Radziwonik-Frączyk et al. [1] about a 20-year-old man with muscular dystrophy who was clinically characterized by gross motor delays, gait disturbances, and difficulty walking and running. Notably, he has been unable to walk on heels, jump or squat since the age of eight. These symptoms worsened again at puberty when he became unable to climb stairs and developed a waddling gait [1]. Genetic testing revealed the homozygous variant c.550delA (p.Thr184Arg) in CAPN3 and a heterozygous CCTG expansion in the CNBP gene [1]. The patient was diagnosed with myotonic dystrophy type 2 (MD2) and calpainopathy [1]. The study is impressive, but some points should be discussed further.
The first point is that the exact length of the CCTG expansion was not recorded [1]. The diagnosis of MD2 requires the documentation of the exact expansion size, not only for an assessment of disease progression, but also for genetic counselling. The exact expansion size is also required to determine the genotype-phenotype correlation. Determination of the exact expansion size should be possible by a combination of routine polymerase chain reaction (PCR), Southern blot analysis and PCR repeat primed assay [2].
The second point is that the findings of electromyography, muscle biopsy and muscle imaging could also be explained by the CAPN3 mutation. Walking difficulties, myalgia, hypotonia could also be due to the calpainopathy. Therefore, it remains questionable whether the index patient indeed had clinical manifestations of MD2.
The third point is that the index patient was not prospectively screened for subclinical or mild multisystem manifestations. As MD2 is a multisystem disease that either occurs early in the course of the disease or becomes a multisystem disease during the course of the disease [3], the index patient should be screened for central nervous system, otologic, ophthalmologic, endocrine, gastrointestinal or renal involvement. Knowing which organs are affected is crucial for the timely initiation of symptomatic treatment. In particular, it is crucial to know whether the patent had cardiac involvement, as this can strongly influence the outcome for MD2 patients.
The fourth point is that it remained unclear why the diagnoses were made so late. Was it due to unavailability of resources or the lack of parental consent?
To summarize, this interesting study has limitations that put the results and their interpretation into perspective. Addressing these limitations could strengthen the conclusions and corroborate the results of the study. The diagnosis of MD2 requires not only a typical phenotype, but also the genotype with the exact number of CCTG repeats.
