Congenital Myopathy as a Phenotypic Expression of CACNA1S Gene Mutation: Case Report and Systematic Review of the Literature

Figures

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  Figure 1. PRISMA flowchart of review.

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  Figure 2. (A). The CACNA1S human gene extends over 73 kb and contains 44 exons (each vertical black line denotes one exon). The position of the start codon (ATG) is indicated. (B). The corresponding protein domains are represented according to the Protein Families (PFAM) database (C). Schematic view of the CACNA1S mutations of patients described in the present work with related grade (mild, moderate, and severe) of phenotype and position (transmembrane, extracellular, or cytoplasmatic) according to UNIPROT (https://www.uniprot.org/uniprotkb/Q13698/entry accessed on 7 June 2023) (D). Schematic view of the CACNA1S-encoded α 1 sub-unit of DHPR. The subunit has a total of four transmembrane domains (I–IV) composed by six segments (1–6) and three intracellular loop domains (loops I–II, loops II–III, and loops III–IV). Patient mutations are indicated with a cross and respective number.

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  Figure 3. Left biceps brachialis muscle biopsy revealed fiber size variability, occasional internal nuclei, and disorganization of intermyofibrillar network (Hematoxylin-Eosin (A), NADH (B), stainings: 200×).

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  Figure 4. Muscle MRI images of axial T1 (I) and Ideal FSE (II) sequences of pelvis (A), thighs (B), and legs (C). MRI images showed: hypotrophy of pelvis muscles with adipose infiltration of gluteus muscles (A.I—white arrows) and tensor fasciae latae muscles (A.I—white arrow heads); hypotrophy of thigh with major involvement of medio-posterior muscles and an adipose infiltration of semitendinosus (B.I and B.II—white arrow heads) and sartorius muscles (B.I and B.II—white arrows); and mild adipose infiltration of peroneus (C.I and C.II—white arrow) and postero tibialis muscles (C.I and C.II—white arrow heads) in legs.

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  Figure 5. Graphic representation of symptoms in all patients and in different phenotypic groups. Muscle weakness: “Mild” indicates proximal and axial muscle weakness while “Severe” indicates generalized muscle weakness. Ophalmoplegia, Scoliosis, ID (Intellectual Disability): “Mild” indicates presence.