Fig. 1: ASC-1 Related Myopathy phenotypical spectrum.

(A) Clinical findings in patients CIII.7 (a), DII.2 (b-f) and EII.4 (g,h). (a) Congenital presentation with neonatal hypotonia (frog position), poor limb movements and respiratory distress requiring tracheostomy and assisted ventilation. He had skin lesions, dysmorphic facial features (i.e flat face; not shown) and tapering fingers. (b-f) Patient DII.2, still ambulant at age 35 years: note severe scoliosis with dorsal lordosis and unbalanced hips (b,d), thoracic deformities (pectus excavatum) and elbow contractures (b) contrasting with prominent joint hyperlaxity (f). Dysmorphic features included large, thick neck and retrognathism and low-set ears (not shown). The skin phenotype was marked by follicular hyperkeratosis, xerosis with scratch lesions, prominent scars (but not keloid) and skin hyperelasticity (c,e). (g,h): The mildest patient (EII.4), still ambulant at 63 years, has proximal amyotrophy, pectus excavatum and dysmorphic facial features (flat face, thick neck, retrognathia). (B) Muscle imaging in two patients revealed predominant involvement of posterior thigh compartment with relative preservation of the semitendinosus muscle. (a-c): Lower limb MRI from a mild patient (BIII.1), still ambulant at age 19 years. Axial T1-weighted images showed mild muscle atrophy and fatty infiltration of glutei, iliopsoas and posterior thigh muscles with major involvement of adductor longus and relative preservation of gracillis, sartorius and semitendinosus muscles (arrows). Note marked increase in subcutaneous adipose tissue. (d-g): Muscle MRI from patient EII.4 (aged 56 years), showed the same pattern, including fatty infiltration of paravertebral muscles (d) and the posterior thigh compartment, notably gluteus maximus, adductor longus and semimembranosus (e,f). Note relative preservation of semitendinosus. Leg muscles showed diffuse involvement (g).