Family 1
Subjects II4 and III5 are the only affected members of a French non-consanguineous family (Figure 1). Subject II4 reported an intentional tremor during adolescence, and presented frequent falls and hand motor weakness from the age of 30 years. Over decades, the weakness has spread in the pelvic and scapular girdle, resulting in disability and wheelchair requirement by the age of 65 years. On examination, she presented severe muscular weakness in the distal lower limbs (1/5 on Medical Research Council (MRC) Scale for muscle strength) and distal upper limbs (2/5 on MRC scale). Proximal weakness was also noted, mostly in the deltoids, biceps brachialis, and psoas iliacus (2/5 on MRC scale), but also in the quadriceps and hamstring muscles (4/5 and 3/5 on MRC scale, respectively). Diffuse wasting and generalized areflexia were present. Sensory complaints were minor and characterized by a diminished vibratory sense in all four limbs. Nerve conduction studies showed severe motor and sensory axonal neuropathy (Table 1). The Creatine Kinase (CK) level was in the normal range (198 UI/L; normal >< 200 UI/L). Her son (III5) developed an intentional tremor, hand motor weakness at the age of 20 years, and had walking difficulties and distal leg weakness from the age of 23 years. Neurological examination at 46 years showed distal muscular atrophy and severe distal weakness in lower limbs. Tibialis anterior and foot extensors were rated 1/5 whereas triceps was rated 2/5 on MRC scale). Mild proximal weakness in upper limbs was also noted (deltoids and biceps brachialis rated 4/5 on MRC scale) and the intrinsic hand muscles were weaker and rated 2/5 on MRC scale. Tendon reflexes were absent. No sensory impairment was noticed. Nerve conduction studies (NCS) and electromyogram (EMG) showed motor and sensory axonal neuropathy (Table 1).