Complexities in Genotype-Phenotype Correlation and Genetic Counseling in Collagen VI - Related Myopathy

Excerpt

To the Editor : Proband was evaluated at 12 y for difficulty in walking and progressive weight gain. He is the first born to a non-consanguineously married couple. He was born at term by vaginal delivery, weighed 2.5 kg (normal) at birth. He was found to have mild motor delay and normal intellect. He walked at 3 y. His language and social milestones were normal. Difficulty in walking was associated with swaying and frequent falls. He also had difficulty in getting up from sitting position and had recurrent respiratory tract infections. On exam, head circumference of 52 cm (normal) was noted. Facial dysmorphism constituting depressed nasal bridge, anteverted nares, downturned angle of the mouth and prognathism were observed. Wasting of small muscles of the hands, laxity, 5th fingers brachydactly and knee joint hypertrophic scarring were noted. He also had obesity, unilateral undescended testis, scoliosis, bilateral shoulder and elbow joints contractures, proximal muscle weakness and diminished deep tendon reflexes (Fig. 1). Creatine phosphokinase was elevated (628 U/L). Muscle biopsy showed dystrophic changes. Electromyography and imaging of the thigh was suggestive of collagen VI-related myopathy (Fig. 2a). A known de novo pathogenic heterozygous variation in COL6A1 gene, c.868G > A (p. Gly290Arg) (NM_001848, HGMD ID CM050215, CM053816) was picked up in exome sequencing. Validation and segregation analysis by Sanger sequencing was performed (Fig. 2b, c, d).

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