Figure 2.

Clinical Features in Kindreds Affected by DCSMA Due to BICD2 Mutations

(A) A severely affected 4-year-old member of AUS1 (IV.5) shows marked wasting of the buttocks and entire lower limb, pes planus, and calcaneovalgus foot deformities but preserved truncal and upper-limb muscle bulk. This child has a wide-based waddling gait and hyperlordotic posture and uses a wheelchair to travel distances of more than a few hundred meters.

(B) AUS1 IV.5, now aged 7 years, shows stable wasting of the lower limbs and stable preservation of upper-limb muscle bulk. His sister (IV.6) shares similar features. Both siblings have required noninvasive nocturnal ventilation since 4 years of age for obstructive sleep-disordered breathing.

(C) MRI of the 32-year-old mother of siblings IV.5 and IV.6 shows a specific pattern of muscle involvement and sparing with or without relative hypertrophy in the upper thigh and hallmark preservation of medial adductors and semitendinosus.

(D) The MRI features of the mother in (C) are identical to those of a 24-year-old male AUSTRIA1 member, who shares the same c.320C>T (p.Ser107Leu) mutation. Members of UK1 and UK2 have more severe muscle involvement, but sparing of the same subset of muscles (e.g., medial adductors and semitendinosus in the upper thigh) is still evident. The lower-limb MRI features are almost identical to those seen in individuals with DYNC1H1-associated DCSMA.