Central Core Disease: Facial Weakness Differentiating Biallelic from Monoallelic Forms

Abstract

Central Core Disease (CCD) is a genetic neuromuscular disorder characterized by the presence of cores in muscle biopsy. The inheritance has been described as predominantly autosomal dominant (AD), and the disease may present as severe neonatal or mild adult forms. Here we report clinical and molecular data on a large cohort of Brazilian CCD patients, including a retrospective clinical analysis and molecular screening for RYR1 variants using Next-Generation Sequencing (NGS). We analyzed 27 patients from 19 unrelated families: four families (11 patients) with autosomal dominant inheritance (AD), two families (3 patients) with autosomal recessive (AR), and 13 sporadic cases. Biallelic RYR1 variants were found in six families (two AR and four sporadic cases) of the 14 molecularly analyzed families (~43%), suggesting a higher frequency of AR inheritance than expected. None of these cases presented a severe phenotype. Facial weakness was more common in biallelic than in monoallelic patients (p = 0.0043) and might be a marker for AR forms. NGS is highly effective for the identification of RYR1 variants in CCD patients, allowing the discovery of a higher proportion of AR cases with biallelic mutations. These data have important implications for the genetic counseling of the families.

A case report of central core disease with repeated foaming at the mouth as the initial symptom

“…[5] Advanced sequencing techniques have proven highly effective in identifying RYR1 mutations in patients with CCD. [6] 2. Clinical material Chen, a 42-day-old male infant, was brought to our hospital on March 1, 2023.…”

“…[ 5 ] Advanced sequencing techniques have proven highly effective in identifying RYR1 mutations in patients with CCD. [ 6 ]…”

Editorial for the Genetics of Muscular Dystrophies from the Pathogenesis to Gene Therapy Special Issue

“…Cotta and co-workers [ 1 ] described clinical and molecular data on a large cohort of Brazilian central core disease (CCD) patients, including a retrospective clinical analysis and molecular screening for RYR1 variants using next-generation sequencing (NGS). The authors analyzed 27 patients from 19 unrelated families, of which 4 had autosomal dominant (AD) and 2 had autosomal recessive (AR) inheritance.…”

“…They also highlight that it is not only important for a complete and precise diagnosis [ 3 , 5 ] to propose timely personalized and pathogenic therapies [ 4 , 8 ], but also to consider potential genetic modifiers [ 6 , 7 ]. We anticipate that this Special Issue will help researchers dismiss concepts that are no longer applicable, such as the presence of homogeneous phenotypes [ 1 , 9 , 10 ] and the concepts of “one gene = one phenotype” to overcome the “single-dimension” paradigm traditionally used to describe genotype–phenotype relationships [ 2 ]…”