Early onset (proximal) LGMD and dystrophinopathies
In western and central Europe, LGMD2I, LGMD2A and LGMD2B are probably the most common LGMD forms. A muscle biopsy including protein expression analysis is usually necessary to distinguish among LGMD subtypes [36, 37]. LGMDs also present with different patterns of muscle involvement on imaging that might help in the genetic diagnosis. An illustration of different muscle imaging findings in LGMD patients is provided in Fig. 4.
Fig. 4 Flowchart showing the approach to LGMD. Most LGMD patients have greater affliction of the posterior rather than the anterior thigh compartment muscles. On the other hand, patients with dystrophinopathy and sarcoglycanopathy often have significant affliction of the quadriceps muscle. Dystrophinopathy often presents with early and marked changes in the gastrocnemii muscles, while patients with sarcoglycanopathy show no affliction of these muscles. Patients with dysferlinopathy most often show posterior thigh and posterior lower leg involvement with sparing of the sartorius, gracilis and biceps femoris. However, muscle affection can be variable, but clinically calf atrophy and absence of scapular winging are commonly present. Calpain-3 and FKRP patients present with predominant posterior thigh and posterior lower leg involvement. Calpain-3 patients usually show marked involvement of the soleus and medial gastrocnemius muscles. Furthermore, calf atrophy and scapular winging are usually observed. Conversely, FKRP patients have a more diffuse involvement of the posterior lower leg muscles, while the tibial anterior muscle is often spared or even hypertrophied

FKRP-related myopathies (LGMD2I)
A few years ago, a novel gene encoding a putative glycosyltransferase, fukutin-related protein (FKRP), was found to be responsible for both a novel form of congenital muscular dystrophy (MDC1C) and for a form of limb girdle muscular dystrophy (LGMD2I) [38, 39]. Recently, we performed a systematic clinical and muscular MRI assessment in several LGMD2I patients and compared these findings with those of other patients with genetically confirmed diagnosis of other forms of autosomal recessive LGMDs or dystrophinopathies [40].
All LGMD2I patients had a characteristic muscular phenotype on MRI of the lower extremities that demonstrated marked signal changes in the adductor muscles, the posterior thigh and posterior calf muscles. Furthermore, data of patients with different clinical disease severity pointed towards a specific temporal pattern. At the pelvic level, the gluteus maximus was involved earlier and more severely than the gluteus medius. At the thigh level the earliest and most severe changes were observed in the adductor (magnus) muscles and the biceps femoris. With further progression degenerative changes were noticed in the remaining hamstring muscles and to a lesser degree in the vastus lateralis and vastus intermedius muscles. Involvement of the vastus medialis and rectus femoris was only observed in the patient with advanced disease, while the sartorius and gracilis muscles were relatively spared. In the lower legs relatively diffuse changes in the medial head of the gastrocnemius and the soleus muscle were observed early in the disease, while involvement of the anterior compartment muscles was only observed in later stages of the disease. The tibialis anterior muscle was usually spared and often hypertrophied.

Calpainopathies (LGMD2A)
Compared with LGMD2I, in patients with LGMD2A, caused by mutation in the calpain-3 gene, we observed a very similar and consistent clinical and muscle imaging phenotype. As in LGMD2I, muscle MRI images have confirmed the clinical observation that in LGMD2A there is early and predominant involvement of posterior compartment muscles such as the gluteus maximus in the pelvis, semimembranosus, biceps femoris and adductor muscles in the thigh, with relative sparing of the vastus lateralis, sartorius and gracilis. These findings were also later confirmed by others [41]. Contrary to LGMD2I, there are, however, some important differences: the vastus lateralis is spared more in LGMD2A compared with LGMD2I; the medial gastrocnemius and soleus muscles are much more selectively involved compared with the diffuse affliction seen in LGMD2I, and hypertrophy of the tibialis anterior muscle is only rarely present in LGMD2A.

Dysferlinopathies (LGMD2B)
Dysferlinopathies, which are genetically characterised by mutations in the dysferlin gene lead to LGMD 2B, distal Miyoshi myopathies and a form of distal anterior compartment myopathy [42, 43]. On MRI, symptomatic patients with dysferlinopathies present with severe dystrophic changes in the anterior and posterior compartments of the thighs with a characteristic sparing of the gracilis and sartorius muscles. In the lower legs, dysferlinopathies predominantly affect the posterior compartment with a relative sparing of the medial head of the gastrocnemius muscle [44–46]. This distinct pattern is different from muscle involvement in LGMD2I and LGMD2A patients in which dystrophic changes in the posterior thigh and posterior calf muscle can frequently be observed [40].

Dystrophinopathies (DMD/ BMD) and sarcoglycanopathies (LGMD2C, D, E and F)
While sarcoglycan deficiencies (LGMD2C, D, E and F) are relatively rare, dystrophinopathies [type Duchenne (DMD) and type Becker (BMD)] are the most common muscular dystrophies worldwide. Therefore, late onset BMD patients or sporadic symptomatic female carriers of DMD often enter the differential diagnosis in sporadic LGMD patients. Furthermore, recently published studies emphasised an overlap between LGMD2I and the group of dystrophinopathies mainly as both often have calf or generalised muscular hypertrophy, and respiratory and cardiac involvement [38, 39]. However, on muscle imaging all our patients with BMD and alpha-sarcoglycanopathy showed pronounced signal changes in the anterior rather than the posterior thigh muscles (as present in LGMD2I patients). In accordance with our results, a predominant affliction of the anterior thigh compartment has been observed in dystrophinopathy and LGMD2D [47–49]. Thus, the relation between knee extensor and flexor involvement might be useful in distinguishing dystrophinopathies and sarcoglycan deficiencies from LGMD2I on muscular MRI. Finally, alpha-sarcoglycanopathy can be differentiated from BMD patients by the greater extent of upper limb involvement [47] and by the different pattern in the lower limbs on muscular MRI [50].