Collagen VI-related myopathy with scoliosis alone: A case report and literature review

Abstract

Background: Scoliosis is a complex three-dimensional deformity of spine and one of the common complications of collagen VI-related myopathy, caused by mutations in collagen type VI alpha 1 chain (COL6A1), COL6A2, and COL6A3 genes. The typical clinical presentations of collagen VI-related myopathy include weakness, hypotonia, laxity of distal joints, contractures of proximal joints, and skeletal deformities.

Case summary: A 28-year-old female presented with scoliosis for 28 years without weakness, hypotonia, laxity of distal joints, and contracture of proximal joints. Computed tomography and magnetic resonance imaging revealed hemivertebra, butterfly vertebra, and the missing vertebral space. Patients underwent orthopedic surgery and paravertebral muscle biopsy. The Cobb angle dropped from 103.4° to 52.9°. However, the muscle biopsy showed neurogenic muscular atrophy with myogenic lesions, suggesting congenital muscular dystrophy. Gene analysis indicated that mutations in COL6A1 (c.1612-10G>A) and COL6A2 (c.115+10G>T, c.2749G>A). Immunohistochemistry staining for collagen VI displayed shallow and discontinuous. Eventually, the patient was diagnosed as collagen VI-related myopathy.

Conclusion: This newly found subtype of collagen VI-related myopathy has no typical manifestations; however, it is characterized by severe scoliosis and congenital vertebral deformity.

Keywords: Case report; Collagen VI-related myopathy; Genetic testing; Neuromuscular diseases; Paravertebral pathology; Scoliosis.

Figure 1

Preoperative imaging examination. A: X-ray of the scoliosis - AP view; B: X-ray of the scoliosis - Perfil view; C: Computed tomography three-dimensional reconstruction of the patient; D: Magnetic resonance imaging of the patient’s entire spine.

Figure 2

Multifidus biopsy results of hematoxylin and eosin staining. A few muscles were slightly reduced in size, round in shape, bundles scattered, widened fiber gap and shrink nuclei, with occasional muscle fissure and connective tissue hyperplasia (orange arrows) (hematoxylin & eosin staining, × 40).

Figure 3

Multifidus biopsy results of dystrophin. A: Positive dystrophin 1 staining of sarcolemma (immunohistochemistry [IHC]: dystrophin-1 staining, × 40); B: Partial sarcolemma dystrophin 2 staining was uneven (IHC: dystrophin-2 staining, × 40); C: Partial muscle sarcolemma dystrophin 3 stained unevenly (IHC: dystrophin-3, × 40).

Figure 4

Multifidus biopsy results of cluster of differentiation 4. A few cluster of differentiation 4 (CD4)-positive staining were seen in the wall and stroma of focal small blood vessels (orange arrows) (CD4 staining, × 40).

Figure 5

Electron microscopy results. A: Some sarcolemma is corrugated, and extracellular matrix arrangement is slightly disordered (orange arrows) (× 6000); B: The inner myofibril arrangement is orderly, but band A is unclear (orange arrows) (× 15000).

Figure 6

Gene mutations in COL6A1, COL6A2. A: Sequencing of collagen type VI alpha 1 chain (COL6A1) gene revealed splicing mutations; B: Sequencing of COL6A2 gene revealed missense mutations; C: Sequencing of COL6A2 gene revealed splicing mutations.

Figure 7

Collagen VI immunohistochemistry. A: This patient muscle membrane stained shallow, broaden and discontinuous (immunohistochemistry [IHC]: collagen type VI alpha (COL6A staining, × 40); B: Another myopathy patient (non-scoliosis) matched by age and sex, staining continuous and dense (IHC: COL6A staining, × 40).

Figure 8

Imaging of halo-pelvic distraction. A: Postoperative X-ray of the spine (AP view); B: Postoperative X-ray of the spine (Perfil view).

Figure 9

Postoperative imaging examination. A: Postoperative X-ray of the spine (AP view); B: Postoperative X-ray of the spine (Perfil view).