While in adults there is a higher proportion of patients with polymyositis than dermatomyositis, in children the converse is true, with dermatomyositis being by far the most common inflammatory myopathy in childhood [35, 36]. Juvenile dermatomyositis is a chronic autoimmune disease characterized by limb girdle weakness, with involvement of neck flexors and extensors muscles and pathognomonic skin rashes. It is a multisystem disorder affecting primarily the muscle and skin due to a capillary vasculopathy. There is a predominance in females that ranges from 2:1 to 5:1 [21, 35, 37].

The diagnostic criteria include symmetrical limb girdle weakness, heliotrope dermatitis and/or Gottron’s papules, increased CK (though it is important to note that some patients may have normal values), muscle biopsy consistent with diagnosis (the characteristic finding is the perimysial atrophy of muscle fibers) and an abnormal EMG [38]. In acute-subacute stages EMG shows prominent presence of fibrillation potentials and or positive sharp waves, with short small MUAPs and early recruitment. In long standing forms it is possible to find CRDs. These findings are more evident in proximal and paraspinal muscles. This last muscle group is the most sensitive and should be evaluated when there is no abnormal finding in other muscles [39]. In more chronic cases the MUAPs may have long durations and increased amplitudes, mimicking a neurogenic disorder. The NCVs are normal unless there is severe muscle atrophy in which case decreased CMAP amplitudes will be observed in conjunction with normal sensory responses.

Currently, EMG and muscle biopsy are not used as frequently for diagnosis of dermatomyositis as in the past, as they are considered invasive studies [40]. Muscle MRI has proven to be a useful method for the diagnosis of dermatomyositis and as a biomarker for treatment response, usually revealing increased T2 signals in affected muscles and subcutaneous tissues [41].

The main therapy is immunosuppressive medications such as corticosteroids, methotrexate or cyclosporine. In some patients who require prolonged corticosteroid use, a secondary proximal muscle weakness may develop, reflecting a steroid myopathy that is associated with selective type 2 fiber atrophy. EMG can be used in such cases to help differentiate among a relapse, refractory dermatomyositis, or a steroid myopathy since dermatomyositis is associated with increased spontaneous activity whereas steroid myopathy is not (see normal EDX group Fig. 22.2) [42].

DMD is the most common form of muscular dystrophy in childhood [43]. Since it is an X-linked disorder it typically affects males, with heterozygous female carriers sometimes showing mild cardiac and muscle symptoms in adulthood; exceptionally, females will have more dramatic phenotypes such as in the setting of concomitant Turner syndrome, unfavorable X-linked inactivation, or relevant chromosomal translocation [44]. DMD most commonly results from an out-of-frame deletion or duplication within the DMD gene, or less commonly, a frameshift or nonsense mutation. Patients exhibit progressive proximal muscle weakness and contractures, eventually losing independent ambulation, developing cardiomyopathy and later death from cardiorespiratory complications [43]. The diagnosis is confirmed with genetic testing. When DNA testing is negative, muscle biopsy may be required to evaluate for the possibility of a mimicking disorder [45]. Typical muscle biopsy findings include absent dystrophin staining with characteristic dystrophic changes (e.g., split fibers, increased internalized nuclei, regenerating fibers, and replacement of muscle by fat and connective tissue). In some cases, it may be necessary to extract RNA to find direct evidence for cryptic splicing defects [46]. Published databases can also guide clinicians as to whether specific mutations are or are not known to be pathogenic, and clinical genetic test reports increasingly make use of such databases to reduce the reporting of the dreaded “variants of unknown significance”. High serum CK levels (typically >20–150 × the upper limit of normal) should trigger the suspicion for this diagnosis, particularly when there is clinical onset after 1.5 years of age, toe-walking, pseudohypertrophy of the calves, and/or a positive Gowers sign [45]. EDX is rarely used in the diagnostic evaluation for Duchenne muscular dystrophy. In those rare instances when it is performed, nerve conduction studies will be normal, while needle EMG may reveal abnormal insertional activity, fibrillation potentials and PSW, with myopathic motor units and an early recruitment pattern, especially in proximal symptomatic muscles. With advancing disease, the CMAP amplitude will decrease, insertional activity will diminish, and the myopathic findings will become more apparent due to progressive muscle atrophy. In endstage muscle it may be difficult to find areas where motor units can be consistently recruited and evaluated.

Becker muscular dystrophy (BMD) also results from dystrophin mutations. However, unlike DMD, patients with BMD show some residual protein expression and activity, due to the association in most cases with in-frame deletions, duplications, and point mutations [43]. Consequently, patients have a milder symptomatology with a later onset compared to DMD.

DMD management requires a multidisciplinary approach. Corticosteroids have been used to slow disease progression, improving and preserving muscle strength and function, prolonging independent ambulation, and delaying the onset of complications such as scoliosis, respiratory decline and cardiomyopathy [45, 47]. Other therapies are emerging with the goal of improving the expression of dystrophin through novel molecular mechanisms. Such novel therapies include ones that transform an out-of-frame to an in-frame mutation via exon skipping induced by an antisense oligonucleotide that was recently provisionally approved by the US Food and Drug Administration; other novel therapies are in development [47–50].

Glycogen storage disease type II, also known as Pompe disease or acid maltase deficiency, is an autosomal recessive lysosomal glycogen storage disorder. It has two main phenotypes, an early onset form presenting during infancy and characterized by generalized hypotonia, weakness, macroglossia, cardiomegaly, hepatosplenomegaly, failure to thrive, and respiratory insufficiency [51]. The late onset form presents with progressive muscle weakness in both pediatric and adult populations that often mimics the phenotype of limb-girdle muscular dystrophy with frequent respiratory complications but usually without heart involvement [52]. The late onset patients are more difficult to recognize since the presentation can include a limb girdle muscular dystrophy pattern, an asymmetric scapular winging, ptosis, and/or asymptomatic hyperCKemia [53]. The muscle biopsy usually shows vacuoles positive for glycogen with PAS staining, but there are also atypical cases without glycogen accumulation [54, 55]. The serum CK is usually elevated, particularly in the infantile form of the disease (<10× upper limit of normal). Due to the phenotypic variability of this disease, particularly in the later onset form, EDX studies can provide important clues for the diagnosis. NCS are normal except in advanced cases with severe muscle atrophy. Needle EMG may demonstrate fibrillation potentials and PSW as well as myotonic discharges. This is seen in paraspinal muscles in half of the children and two-thirds of adults with this disease. The examination of this group of muscles is important since it may be the only site revealing abnormalities in the EDX [56]. It is important also to mention that this group of patients has electrophysiological myotonia but no clinical signs of it. The diagnosis is usually confirmed by analyzing the enzyme activity in the blood using a dried blood spot testing, followed by genetic testing [52]. The advent of enzyme replacement therapy (ERT) has changed the outcome of the infantile onset patients. Without ERT the early onset has a high mortality with death by the age of 1 year [51]. ERT has also improved symptomatology for patients with late onset Pompe [57].

The congenital muscular dystrophies (CMD) are a heterogeneous group of disorders. The diagnosis is usually made by the clinical exam, CK levels, which can range from normal to 6–10× high, brain MRI, and immunohistochemical staining in the muscle biopsy. An abnormal brain MRI may be seen in a subset of CMD patients, especially the dystroglycanopathies and merosinopathies. Muscle biopsy shows dystrophic features and may show abnormalities on immunohistochemical staining for merosin and or alpha-dystroglycan (aDG). It is the second most common reason for requests for EMG studies in floppy infants admitted to the NICU for suspected primary muscle disorders, after congenital myopathies [58]. The most common CMD subtype is MDC1A (primary merosin deficiency) [59]. The findings include generalized weakness, early contractures and respiratory insufficiency, high serum CK, diffuse white matter changes on brain MRI and deficient merosin on muscle biopsy [43, 59]. Partial merosin deficiency can be seen in some patients with LAMA2 mutations and also in the alpha-dystroglycanopathies due to abnormalities in protein glycosylation of aDG. The findings include increased CK and frequent eye and brain malformations that range from abnormalities in the posterior fossa to lissencephaly. The most severe classic phenotypes are muscle-brain-eye disease, Walker-Warburg syndrome and Fukuyama CMD [60]. Other CMDs include the rigid spine syndrome due to mutations in SEPN1 and the collagen VI related myopathies (Bethlem myopathy and Ullrich CMD). The latter is characterized by congenital hip dislocation, congenital torticollis, and joint hyperlaxity with development of early contractures and scoliosis and generalized muscle weakness [61].

Nerve conduction studies are usually normal except for patients with primary merosin deficiency. In this group there is a slowing in the conduction velocities of the motor nerves with normal amplitude and normal sensory studies [62]. Motor neuropathy is often associated with severe form of MDC1A. Also there has been a report of borderline low NCVs in a young patient with Ullrich CMD (due to mutations in COL6) [63]. EMG does not demonstrate the abnormal spontaneous activity that can be seen in other primary myopathies and more significantly in neuropathies. The typical “myopathic” potentials when demonstrated are usually present in more proximal muscles. One report describes brief repetitive decreasing discharges in distal muscles post-electrical stimulation. These were of high frequency (90–300 Hz) and short duration (median 61.5 ms) with the shape of single motor response. They were not elicited by muscle percussion and were different from myotonia due to the lack of the waxing and waning feature [63].

Congenital myopathies are a heterogeneous group of inherited muscle diseases that vary in age of onset, clinical features, morbidity and mortality. Although the classical description is of patients with onset in infancy, they can present in a wide range of ages. Signs that can help to establish the diagnosis include: lack of antigravity movements, ophthalmoplegia, ptosis, high arched palate, arthrogryposis, hip dysplasia, and lower facial muscle weakness with open tented mouth. The serum CK is typically within the normal range but can be slightly elevated. The diagnosis has been historically established by muscle biopsy, as the different types are classified according to pathological findings. As genetic testing has become more widely available there is a trend to classify them by gene, since numerous genes are now associated with multiple phenotypes and histopathological findings [2]. The different histological subtypes include:

Core myopathy. The muscle biopsy reveals areas lacking enzyme activity with oxidative stains such as SDH and NADH, hence, devoid of mitochondria. This category may further be subdivided into central core disease due to dominant mutations in the RYR1 gene (90% of cases), minicore myopathy without ophthalmoplegia due to mutations in SEPN1 and minicores with ophthalmoplegia due to recessive mutations in RYR1 [64]. Other rare causes of core myopathy including mutations in MYH7, ACTA1, and CCDC78.

Congenital fiber-type disproportion. This term refers to the presence of significantly smaller type I fibers compared with type II without features suggestive of other subtypes of congenital myopathy. A pure CFTD is associated with mutations in RYR1, SEPN1, ACTA1, TPM2 and TPM3. Clinically, CFTD overlaps with other types of congenital myopathies, but the phenotype is typically milder than the other subtypes [64].

Nemaline myopathy (NM) is diagnosed when the classic nemaline rods are observed on Gomori trichrome stain and on electron microscopy of a muscle biopsy specimen. Clinically, there is severe congenital NM, intermediate congenital NM, typical congenital NM, childhood/juvenile onset NM and adult-onset NM. There are at least 11 genes within this group. The most common are those in NEB causing a recessive disease and in ACTA1 causing a dominantly inherited NM, typically due to de novo mutations. The characteristic features in this group include bulbar muscle involvement, a myopathic face (open mouth, tented lips, excessive drooling), and a high arched palate, with preservation of extraocular movements [64].

Centronuclear myopathy (including myotubular myopathy) can be caused by mutations in six genes identified to date (MTM1, DNM2, BIN1, SPEG, TTN, and RYR1). Muscle biopsy is characterized by centralized nuclei in at least 25% of the fibers with abnormal central oxidative aggregate staining with SDH and NADH. Certain genes are associated with particular features on muscle biopsy. With DNM2 mutations there is often a “spoke on wheel” appearance with oxidative stains. BIN1 mutations tend to present with clusters of central nuclei. Necklace fibers have been related to mutations in MTM1 and correspond with internalised nuclei within a desmin positive stain ring [64].

EDX in congenital myopathies has a sensitivity of 36% in infants (<2 years of age) with a false negative rate of 25%. The presence of a “myopathic pattern” in a newborn is extremely low [20, 65]. The use of EMG in this age group has been largely replaced by muscle biopsy and genetic studies, but in some cases EMG may still yield useful diagnostic information. In patients >2 years of age there are no characteristics findings for most of the congenital myopathies. The NCS are normal with normal F-responses. The needle EMG will show MUAPs of small amplitude, short duration and polyphasic potentials with an early recruitment and no spontaneous activity [65]. Centronuclear myopathies can represent an exception since fibrillations, positive sharp waves, and more rarely complex repetitive discharges can be seen on needle EMG [13, 66]. The association of myopathic and myotonic findings have been reported in nemaline myopathy [33]. Abnormal repetitive nerve stimulation testing and other features of a NMJ disorder have been observed in cases of congenital myopathy, including those due to mutations in DNM2, MTM1, RYR1, TPM2, TPM3 and KLHL40 [67–72].

The most common is myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2) and they both share prominent clinical and electrical myotonia.

DM1 is an autosomal dominant disease caused by a CTG trinucleotide expansion in the untranslated region of the dystrophia myotonica-protein kinase (DMPK) gene on chromosome 19q13.3 [75–77]. Anticipation is characteristic in this disease with an increasing number of CTG repeats in subsequent generations, especially with maternal inheritance, with large CTG repeats of 1000–4000 typically occurring in the congenital form of DM1. Although cranial muscle weakness and wasting and predominantly distal muscles weakness and wasting are the main features of this disease along with myotonia, other systems can be involved leading to cognitive dysfunction, hypersomnia, dysphagia, cardiac arrhythmias, muscle pain, cataracts, respiratory insufficiency, insulin resistance and diabetes, and cancer [78, 79]. The childhood-onset form of DM1 can present as early as the neonatal period with muscle weakness and respiratory insufficiency and although these children improve with time, they have long term global developmental delays.