Bethlem myopathy 1 (BTHLM1; MIM 158810) and Ullrich congenital muscular dystrophy 1 (UCMD2; MIM 254090) are two related disorders caused by mutations in the COL6A1, COL6A2 or COL6A3 gene. Bethlem myopathy 2 (BTHLM2; MIM 616471) and Ullrich congenital muscular dystrophy 2 (UCMD2; MIM 616470) are caused by mutations in the COL12A1 gene.

Bethlem myopathy is an autosomal dominant disorder characterized by mild to moderate proximal muscular weakness and mild muscle atrophy. Contractures of the elbows, ankles, and flexion contractures of the last four fingers are present and range in severity. There may be moderate weakness of the trunk muscles and diaphragm. The age of onset ranges from birth to adulthood. The disorder is slowly progressive and about one half of the patients require ambulatory support after the fifth decade.

Ullrich congenital muscular dystrophy was originally described as an autosomal recessive disorder but heterozygous dominant negative mutations have also been described. Ullrich congenital muscular dystrophy is more severe than Bethlem myopathy and is characterized by neonatal hypotonia, severe muscular weakness, and generalized muscular atrophy. Patients with Ullrich congenital muscular dystrophy have delayed motor milestones and difficulty with ambulation. Patients also present with proximal joint contractures, spinal rigidity, scoliosis, kyphosis, and distal joint laxity. Weakness of the trunk muscles and diaphragm can lead to respiratory insufficiency. Ullrich congenital muscular dystrophy is progressive and many patients lose the ability to ambulate.

The Bethlem myopathy and Ullrich congenital muscular dystrophy NGS panel consists of four genes: COL6A1, COL6A2, COL6A3 and COL12A1.

Copy number variation (CNV) analysis of the Bethlem myopathy and Ullrich congenital muscular dystrophy genes is also offered as a panel. Additionally, CTGT offers a comprehensive test (both NGS and CNV panels) for these genes. Panel genes are also offered as individual sequencing and deletion/duplication tests unless otherwise indicated.