Figure 1. Distinctive clinical signs.

(A) The clinical phenotype in early childhood was recognizable by predominantly axial weakness, deltoid and inner thigh amyotrophy (“bracket-like thighs”) (A.a and A.b) and spinal rigidity identifiable upon specific examination (A.c and A.d). Axial rigidity was typically more prominent in the cervicodorsal spine (A.c and A.d), with relative or full preservation of lumbar spine flexion (A.d). (B) Typical moderate patient at ages 11 (B.a and B.b) and 14 years (B.c–B.e). Often subtle until late childhood, the full phenotype usually became apparent around puberty. Body weight decreased dramatically, leading in some cases to an apparent loss of subcutaneous adipose tissue (lower limbs in B.c and B.d) and a cachexia phenotype. Most patients developed scoliosis (B.e), which required adapted bracing to avoid thorax compression (Garchois brace, B.c and B.d). SEPN1-RM scoliosis is recognizable due to dorsal lordosis leading to pseudo-scapular winging, lateral trunk deviation with compensatory contralateral neck shift, and horizontally aligned hips. (C) Scoliosis progression despite bracing often required arthrodesis (moderately affected patient before [C.a] and after [C.b] spinal fusion).