Abstract
Background: Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of genetic muscular dystrophies, involving autosomal recessive (LGMD R) and dominant (LGMD D) subtypes. The recessive forms are far more common than dominant, particularly in children. The clinical course in this group is characterized by progressive proximal weakness, initially in pelvic and after in shoulder-girdle musculature, varying from very mild to severe degree. Significant overlap of clinical phenotypes, with clinical and genetic heterogeneity, constitutes the rule for this group of diseases. Muscle biopsies are useful for histopathologic and immunolabeling studies, and DNA analysis is the gold standard to establish the specific form LGMD.
Objectives: The aim of this study was to characterize the clinical, histological and molecular aspects in children with LGMD who attend a big public neuromuscular centre in our country to determine the frequency of different forms.
Results: Thirty-nine patients were enrolled in this study and 34 were classified as LGMD. The female to male ratio was 3:1. The mean age at onset of the disease was 6 years (2-13 years). The first sign of the disease were related to a proximal muscular involvement in lower limb, including: frequent falls (22 patients), difficulty in climbing stairs (12 patients) and difficulty to rise from the floor (2 patients). In three patients, the first sign was walking on tiptoe. All patients showed normal milestones and were able to walk before 18 months of age. CK level was elevated in all cases. Of the 34 cases defined LGMD, the frequency found were: 15(44%) Sarcoglycanopathies (LGMD Sarcoglycan-related); Five (15%), Calpainopathy (LGMD Calpain3-related); Five (15%) Dysferlinopathy (LGMD Dysferlin-related) and two (6%) LGMD FKRP-related. In 7/34 patients (21%) it was not possible to define the specific subtype, despite the techniques used. Calf hypertrophy, winging of the scapula and scoliosis were the most characteristic signs in Sarcoglycanopathies. In FKRP-related forms, calf hypertrophy was also observed. Atrophy of posterior compartment of thighs is frequent in children with Dysferlinopathy and could suggest the diagnosis. In Calpainopathy winging of the scapulae and contractures in Achilles tendons were the more important findings. Muscle biopsy showed a dystrophic pattern in all cases, more intense in Sarcoglycanopathies and LGMD FKRP-related.
Conclusions: Our study on LGMD in children demonstrates that Sarcoglycanopathy is the most frequent form of LGMD, particularly in most severe forms. Because of clinical findings overlapping and unspecific pattern in muscle biopsy, for a correctly identify of the subtype, mutation screening through a myopathies panel or exome sequencing is essential.
Descriptors: 1.Muscular dystrophy; 2. Muscular dystrophy Limb-Girdle/classification; 3. Muscular dystrophy Limb-Girdle/genetic; 4.Muscular dystrophy Limb-Girdle/pathology; 5. Child; 6. Biopsy.