Contrary to RYR1- and collagen 6A-related disorders, which have marked affliction of the anterior thigh, in most other CM forms the posterior rather than anterior thigh compartment muscles are affected. SEPN1 patients, often presenting as a rigid spine (multi-minicore) myopathy, typically show a selective affliction of the sartorius and posterior compartment muscles and a relative sparing of the quadriceps and the gracilis muscle [25]. In patients with dynamin 2-related autosomal dominant centronuclear myopathy (DNM2-CNM), muscle imaging shows predominantly distal lower leg muscle affliction (medial head of the gastrocnemius, soleus), milder involvement of the posterior thigh compartment (mostly the biceps femoris and semimembranosus muscles) and the gluteus minimus muscle. The sartorius and gracilis are often spared [65]. Congenital (nemaline) myopathies related to ACTA1 gene mutations show predominantly distal anterior lower leg and mild diffuse thigh compartment involvement. On the other hand, nebulin gene-associated nemaline myopathies often spare the thigh muscles and show selective distal involvement of the soleus and tibial anterior muscles [66]. A useful flowchart for the differential diagnosis of CM using muscle imaging is provided in Fig. 7.
Fig. 7 Flowchart showing a useful approach to the differential diagnosis of congenital myopathies. We highly recommend systematically analysing muscle imaging findings beginning with the thigh muscles. The first distinction should be made according to the relation of posterior to anterior thigh muscle involvement. Most CMs show greater affliction of the posterior rather than the anterior thigh muscles. In the second step, the same relation should be assessed in the lower legs. Predominant posterior thigh and posterior lower leg involvement with sparing of the gracilis and sartorius but marked affliction of the soleus and medial gastrocnemius is observed in DNM2-CNM. Predominantly posterior thigh with marked affliction of the sartorius and predominantly diffuse posterior lower leg involvement are typical findings of SEPN1-related CM. Posterior thigh but anterior leg involvement was observed in CM patients with ACTA1 mutations. On the other hand, marked anterior thigh affliction is seen in RYR1- and collagen 6A-related CM. In addition, RYR1 patients show sparing of the rectus femoris, gracilis and biceps femoris and often marked affliction of the soleus muscle, while patients with a collagen 6A defect show a special rim with the beginning of degeneration within the rectus femoris muscle and a degenerative rim between the soleus und gastrocnemius muscles. Typical muscle imaging findings of patients with proven mutations in the DNM2, SEPN1, ACTA1, RYR1 and collagen 6A1 are provided