Orofacial Muscle Weakening in Facioscapulohumeral Muscular Dystrophy (FSHD) Patients.

Dimitrios Konstantonis,Maria Svingou,Kyriaki Kekou,Petros Papaefthymiou,Nikoleta Konstantoni,Anastasia Margariti,Heleni Vastardis,Maria Athanasiou,Angeliki Panousopoulou

doi:10.3390/children9010096

Abstract

Background: Facioscapulohumeral muscular dystrophy is the third most commonly found type of muscular dystrophy. The aim of this study was to correlate the D4Z4 repeat array fragment size to the orofacial muscle weakening exhibited in a group of patients with a genetically supported diagnosis of FSHD. Methods: Molecular genetic analysis was performed for 52 patients (27 female and 25 male) from a group that consisted of 36 patients with autosomal dominant pedigrees and 16 patients with either sporadic or unknown family status. The patients were tested with the southern blotting technique, using EcoRI/Avrll double digestion, and fragments were detected by a p13E-11 telomeric probe. Spearman’s correlation was used to compare the fragment size with the degree of muscle weakening found in the forehead, periocular and perioral muscles. Results: A positive non-significant correlation between the DNA fragment size and severity of muscle weakness was found for the forehead (r = 0.27; p = 0187), the periocular (r = 0.24; p = 0.232) and the left and right perioral (r = 0.29; p = 0.122), (r = 0.32; p = 0.085) muscles. Conclusions: Although FSHD patients exhibited a decrease in muscular activity related to the forehead, perioral, and periocular muscles the genotype–phenotype associations confirmed a weak to moderate non-significant correlation between repeat size and the severity of muscle weakness. Orofacial muscle weakening and its association with a D4Z4 contraction alone may not have the significance to serve as a prognostic biomarker, due to the weak to moderate association. Further studies with larger sample sizes are needed to determine the degree of genetic involvement in the facial growth in FSHD patients.

Highlights

Facioscapulohumeral Muscular Dystrophy (FSHD, MIM#158900) is one of the most common types of muscular dystrophy, which is inherited in autosomal dominant pattern.FSHD has an estimated prevalence of 1:20,000, an insidious onset, and is characterized by the progressive weakness of the facial, shoulder girdle and foot extensor muscles [1].FSHD is the third most common type of inherited muscle disease after Duchenne muscular dystrophy and myotonic dystrophy [2]
Patients with FSHD phenotype were examined by two neurologists, familiar with the diagnosis of FSHD.Σθβ
We excluded patients with the typical facioscapulohumeral phenotype without FSHD 4q35 deletion as we considered them to have limb-girdle muscular dystrophy, facial sparing scapulohumeral dystrophy or classical FSHD2 phenotype without an EcoRI/BlnI-fragment smaller than 40 kb

Summary

Introduction

Facioscapulohumeral Muscular Dystrophy (FSHD, MIM#158900) is one of the most common types of muscular dystrophy, which is inherited in autosomal dominant pattern.FSHD has an estimated prevalence of 1:20,000, an insidious onset, and is characterized by the progressive weakness of the facial, shoulder girdle and foot extensor muscles [1].FSHD is the third most common type of inherited muscle disease after Duchenne muscular dystrophy and myotonic dystrophy [2]. Facioscapulohumeral Muscular Dystrophy (FSHD, MIM#158900) is one of the most common types of muscular dystrophy, which is inherited in autosomal dominant pattern. FSHD has an estimated prevalence of 1:20,000, an insidious onset, and is characterized by the progressive weakness of the facial, shoulder girdle and foot extensor muscles [1]. FSHD is the third most common type of inherited muscle disease after Duchenne muscular dystrophy and myotonic dystrophy [2]. There are several estimations about the epidemiology of the FSHD with recent studies suggesting a prevalence of approximately 1 in 15,000 people. According to recently conducted studies, large phenotypic variability is connected with heterozygote subjects carrying D4Z4 alleles of different sizes [4,5,6]. FSHD has a variable age of onset that can occur from infancy to adult life along with a rather benign course and a strong penetrance

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