BACKGROUND
While genetic testing panels are currently done earlier as a part of the diagnostic workup when genetic myopathy is suspected, they don’t always yield a definite genetic diagnosis. In these cases, pathological correlation may be helpful in determining the significance of detected genetic variants.
AIM
We present a case of hereditary myopathy with inconclusive genetic testing and final diagnosis clarified by a muscle biopsy.
CASE DESCRIPTION
A 56-year-old female reported slowly progressive difficulties with climbing stairs and standing up from a seated position starting 5 years prior to presentation. She also endorsed milder difficulties with overhead movements while using her arms. No ocular, bulbar, or respiratory symptoms were reported. Family history was notable for a son who passed away at the age of 4 due to a congenital myopathy of unknown nature. On examination, she had mild weakness of bilateral shoulder abduction, elbow extension, hip flexion, and extension, with normal bulk, tone, reflexes, and sensation.
RESULTS
CK was normal (72 U/L). Electromyogram revealed a myopathic process. Genetic testing revealed a pathogenic heterozygous variant in TPM3 gene [c.857A>C (p.*286Serext*57)] and a variant of uncertain significance in BIN1 [c.221C>T (p.Ala74Val)] gene. The significance of the reported BIN1 variant is currently unknown but it is predicted to be disruptible. While TPM3 mutations can cause autosomal dominant myopathies, this specific TPM3 variant is reported in autosomal recessive cases. Mutations in either gene can cause congenital myopathy. A muscle biopsy was done and demonstrated nemaline rods with type I fiber predominance without central nuclei, consistent with the diagnosis of autosomal dominant nemaline myopathy due to TPM3 mutation.
CONCLUSIONS
We emphasize the diagnostic importance of muscle biopsies when the genetic test findings do not reveal a definite answer. We also report that the TPM3 variant [c.857A>C (p.*286Serext*57)] may cause an autosomal dominant myopathy, not just an autosomal recessive one.