To present a case of a non-Native American patient diagnosed with STAC3-related congenital myopathy, carrying the recurrent variant identified in the Lumbee people.

STAC3-related congenital myopathy (STAC3-CM), originally identified in the Lumbee people as Native American myopathy, is now recognized in multiple populations worldwide. This disorder is characterized by muscle weakness, ptosis, myopathic facies, and other musculoskeletal abnormalities. Notably, the condition is associated with increased susceptibility to malignant hyperthermia. A homozygous missense variant (c.851G>C; p.Trp284Ser) in STAC3 segregates with this myopathy in Lumbee families. This variant was particularly described in South Africa. In Brazil, two other cases with this variant were reported, with a phenotype similar to that of the patient in this report.

A 14-year-old female patient from an indigenous Guarani community in southern Brazil, was referred to the Medical Genetics Service at Hospital de Clínicas de Porto Alegre for investigation of developmental delay and neonatal hypotonia. Perinatal complications included seizures and feeding problems. Other findings comprised a submucous cleft palate for which she underwent palatoplasty and experienced malignant hyperthermia, conductive hearing loss, thoracic scoliosis, and myopathic facies characterized by a long face, open mouth, and bilateral ptosis. Examination revealed global hypotrophy and proximal muscle weakness, with a positive Gowers sign. Electromyography suggested primary chronic muscle dysfunction with significant involvement of the proximal musculature. A Neuromuscular Sequencing Panel (Invitae) was performed and revealed a homozygous pathogenic variant in STAC3: c.851G>C (p.Trp284Ser). 

We reported a case of STAC3-related myopathy in a Guarani Mbya patient caused by c.851G>C variant in homozygosity. Guarani Mbya people are an inbred Indigenous population of South America, supporting that c.851G>C could have been distributed in America by ancient migrations. Further studies are needed to understand the distribution and prevalence of STAC3-CM among these populations.