Megaconial congenital muscular dystrophy: Same novel homozygous mutation in CHKB gene in two unrelated Chinese patients.

Megaconial congenital muscular dystrophy (CMD) is a rare form of congenital muscular dystrophy attributed to an autosomal recessive CHKB mutation. We report two unrelated Chinese girls with Megaconial CMD who harbored the same novel homozygous CHKB mutation but exhibited different phenotypes. Patient 1, who is now 8 years old, has autism, intellectual disabilities, mild girdle weakness, and characteristic muscle biopsy with COX-negative fibers. Patient 2, now 12 years old, has limited intelligence and marked weakness, with scoliosis, hip subluxation and early loss of ambulation. Both exhibited mildly elevated creatine kinase levels, have relative sparing of adductor longus and extensor digitorum longus on MRI leg muscles, and a c.598del (p.Gln200Argfs*11) homozygous CHKB loss-of-function mutation. Their parents are heterozygous carriers. This is the first report of Megaconial CMD in Chinese patients demonstrating the pathogenicity of the identified homozygous CHKB variant. A case review of all previously reported patients of different ethnicities is also included.