Central Core Disease: Facial Weakness Differentiating Biallelic from Monoallelic Forms

Area of Science:

• Genetics
• Neuromuscular Disorders
• Molecular Biology

Background:

• Central Core Disease (CCD) is a genetic neuromuscular disorder.
• Typically characterized by cores on muscle biopsy and predominantly autosomal dominant (AD) inheritance.
• Disease presentation varies from severe neonatal to mild adult forms.

Purpose of the Study:

• To analyze clinical and molecular data from a large cohort of Brazilian CCD patients.
• To screen for RYR1 variants using Next-Generation Sequencing (NGS).
• To investigate the frequency of autosomal recessive (AR) inheritance in CCD.

Main Methods:

• Retrospective clinical analysis of 27 patients from 19 unrelated families.
• Molecular screening for RYR1 variants via Next-Generation Sequencing (NGS).
• Analysis of inheritance patterns: autosomal dominant (AD), autosomal recessive (AR), and sporadic cases.

Main Results:

• Biallelic RYR1 variants were identified in approximately 43% of analyzed families (6 out of 14).
• This suggests a higher frequency of AR inheritance than previously expected.
• Facial weakness was significantly more common in biallelic (AR) than monoallelic (AD) patients (p=0.0043), potentially indicating AR forms.

Conclusions:

• Next-Generation Sequencing (NGS) is highly effective for identifying RYR1 variants in CCD.
• The study identified a higher proportion of AR CCD cases with biallelic mutations.
• Findings have significant implications for genetic counseling in CCD families.