2.1.3 Limb-girdle muscular dystrophies (LGMDs)

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 recessive forms [29].

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 LGMD, intellectual disability has been reported [31].

## 2.1.4 Facioscapulohumeral muscular dystrophy (FSHD)

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 with FSHD require mechanical ventilation [23].

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 [26], with no significant progression.

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

retinal vasculopathy characterized by aneurysmal dilatations and exudation, which can cause retinal detachment or blindness; loss of high-frequency hearing, usually asymptomatic; hearing loss; and intellectual disability and seizures in infants with FSHD [32, 33].

A careful, complete, and thorough clinical examination along with laboratory investigations provides more information necessary for management of patients with muscular dystrophy, differentiates between the type of muscular dystrophy, and directs to subsequent analyses.
