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Título

CHALLENGES IN THE DIAGNOSIS OF COLLAGEN VI-RELATED DYSTROPHIES: A CASE REPORT

Apresentação do caso único

An 8-years-old boy, presented with a history of hypotonia since he was 3 months old, started sitting without support with 1 year old and walked at 3 years old. He had normal cognitive development, no other comorbidities, non-consanguineous parents and no family history. Physical examination showed several keloid scars, frequent falls, and grade 4 flaccid and areflexia tetraparesis, predominantly proximal and crural. Initial investigation demonstrated normal CPK and ENMG with myopathic pattern. Muscular dystrophy genetic panel with NGS analysis of 10 genes was collected without changes. Muscle biopsy showed dystrophic histological changes, with normal immunohistochemical. A new NGS panel was tested for muscular dystrophies, myopathies and myasthenias, with a heterozygous variant, probably pathogenic, in the COL6A1 gene, c.806G>A:p.(Gly269Glu); confirming the diagnosis of collagen VI-related dystrophy.

Discussão

Collagen VI-related dystrophies are caused by dominant or recessive mutations in the COL6A1, COL6A2 and COL6A3 genes, with two classic phenotypes: Ullrich, more early and severe (motor symptoms severe onset in adolescence and respiratory muscle weakness appearing in mid-teenage years); and Bethlem, with later and milder presentation (a variable degree of muscle weakness, affecting the legs especially, slowly progresses over time with
respiratory muscles mildly affected, and problems related to respiratory insufficiency very rare and limited to the late adult years). Some tips for clinical suspicion of COL6 deficiency are presence of skin changes; distal hyperextensibility and history of congenital hip dislocation. Previous studies indicate that CK levels are normal in most patients and histological findings are varied and uninformative. A characteristic that helps in the diagnosis is the finding of the “sandwich” sign on muscle MRI. The diagnosis is confirmed by genetic sequencing, which a diagnostic yield of 60% in neuromuscular diseases. Our patient is in an age range that is still undefined in the Ullrich and Bethlem spectrum.

Comentários finais

Nowadays, with clinical and radiological suspicion of collagen VI-related dystrophies, appropriate genetic test can confirm the diagnosis.

Referências

Foley AR, Mohassel P, Donkervoort S, et al. Collagen VIRelated Dystrophies. 2004 Jun 25 [Updated 2021 Mar 11]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews®️ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024.
Kwong AK et al. Collagen VI-related myopathies: clinical variability, phenotype-genotype correlation and exploratory transcriptome study. Neuromuscul Disord. 2023 May;33(5):371-381. doi: 10.1016/j.nmd.2023.03.003.
Zanoteli E et al. Clinical features of collagen VI-related dystrophies: A large Brazilian cohort. Clin Neurol Neurosurg. 2020 May;192:105734. doi: 10.1016/j.clineuro.2020.105734.

Palavras Chave

Collagen VI-related dystrophies; Congenital Muscular Dystrophy; neuromuscular