2.2 Laboratory investigations

muscle (a characteristic pattern called "Popeye arms." A rigid spine is also present

LGMDs represent a group of muscular conditions with autosomal dominant or autosomal recessive inheritance, characterized by a typical pattern of slowly progressive, proximal weakness which involves shoulder and pelvic girdle muscles [18, 19]. Different subtypes of LGMDs have been described, with a wide clinical spectrum affecting various age groups. LGMDs with autosomal dominant inheritance are referred as LGMDs1 and recessive forms, as LGMDs2. LGMDs1 forms have, generally, a later onset and a milder course compared with autosomal reces-

The most affected muscle groups are proximal muscles, namely, the muscles of the shoulders, upper arms, pelvis, and thighs. The clinical picture can vary among different subtypes of FSHD, even within the same family [29]. The onset of clinical features can be at any age and worsen with time. The first symptoms include abnormal gait (waddling gait, walking on the feet balls) and difficulties in running and standing up [29]. The muscle weakness slowly progresses, and, in later stage of the disease, the patients may be wheelchair bound. Other clinical features include scapular wings, lumbar lordosis, scoliosis, calf muscle hypertrophy and joint stiffness, that restrict movement of the elbows, hips, knees, and ankles [30]. Cardiomyopathy was reported in some forms of LGMD, and some patients may present respiratory difficulties which can vary from mild to severe. In some rare forms of

FSHD is a genetic muscular disorder with autosomal dominant inheritance and a

late onset; the disease has a slow progression and a high degree of phenotypic variability and side-to-side asymmetry [30]. The muscle weakness involves initial, facial, scapular, and proximal limb muscles (mimetic muscles, serratus anterior, rhomboid muscles, biceps, and triceps) [21]. The most frequent initial symptom is the inability to lift arms over shoulder height. Then, the weakness progress to lower limbs, typically the distal musculature first (tibialis anterior and gastrocnemius), and later more proximal muscles (quadriceps and hamstrings) and the pelvic girdle are involved [21]. The abdominal and paraspinal muscles can be affected, causing an exaggerated lumbar lordosis or camptocormia (bent spine syndrome) [22]. Pectus excavatum is another common feature in FSHD [22]. The risk to become wheelchair bound is high in the second decade for patients with a more severe infantile form and after the age of 50 years in about 20% of patients [23].

The respiratory involvement varies from 0 to 13% of patients with FSHD in different studies [24] and is caused by the loss of core/trunk muscles. It is present mostly in patients with pelvic girdle weakness who are wheelchair bound or with a marked paraspinal involvement or kyphoscoliosis. Between 1 and 8% of patients

Cardiac involvement is not common in FSHD. 5–10% of patients can present supraventricular arrhythmias, mostly asymptomatic [25]; an incomplete right bundle branch block has been found in approximately one-third of patients in one study

Some extramuscular manifestations have been described in patients with FSHD, almost always in the cases with the smallest number of residual D4Z4 units. They include retinal vascular changes (peripheral telangiectasia); Coats disease, a severe

causing a severe lumbar lordosis [27].

sive forms [29].

Muscular Dystrophies

2.1.3 Limb-girdle muscular dystrophies (LGMDs)

LGMD, intellectual disability has been reported [31].

2.1.4 Facioscapulohumeral muscular dystrophy (FSHD)

with FSHD require mechanical ventilation [23].

[26], with no significant progression.

12

When a muscular dystrophy is suspected, blood enzyme test and a variety of laboratory test can be used for confirmation of clinical diagnosis. The blood serum samples are used to determine the level of specific enzymes known to have a high blood serum levels when a dystrophic process is present:

i. Creatine kinase (CK) also known as creatine phosphokinase (CPK), an intracellular enzyme found with relative predominance in skeletal muscle, is considered as the most specific and sensitive marker of muscle disease. Normal reference value of CK ranges between 60 and 174 IU/L into blood serum [13, 14]. Elevated level of CK could suggest a muscle disease before symptoms of muscular dystrophy become evident [33, 34]. In early stages of the muscle disease, CK levels are 20–300 times greater than normal levels and tend to decrease with the muscle damage [15]. In male DMD patients, the serum CK level is markedly elevated due to muscle degeneration [17] with less elevation level noted in BMD patients. Recent studies show that losses of lung function in DMD patients determine the high level of CK in blood serum [35].

The level of CK has been found higher in other types of MD like limb-girdle muscular dystrophy (LGMD) [17] and could serve as useful indicator being able to discriminate between autosomal recessive and dominant types of LGMD, knowing that CK level recessive types of MD are higher than dominant ones. Also, evaluation of CK level is a useful screening tool for female DMD carrier.

It is interesting to note that not all cases of MD show a high level of CK. For example, in Ullrich congenital muscular dystrophy, Emery-Dreifuss muscular dystrophy, and Bethlem myopathy, the level of CK may be normal or slightly increased [22].

ii. Aldolase, transaminases (alanine aminotransferase ALT and aspartate aminotransferase AST), and lactate dehydrogenase (LDH) are other muscle enzymes also reported with a rise level in blood serum [18] when a muscular dystrophy is suspected.

Also, from the blood collected on anticoagulant (EDTA), total genomic DNA is isolated for further genetic tests used to confirm the diagnosis.

Other laboratory tests like electromyography, magnetic resonance imaging (MRI), combined with muscle biopsy, and genetic tests contribute for toward a diagnosis.
