Clinical predominance of proximal upper limb weakness in CMT1A syndrome

We report an Austrian family with proximal muscle weakness and wasting pred ominantly of the shoulder girdle musculature, normal or slightly reduced di stal muscle power, mild foot deformity, absent or reduced tendon reflexes i n the lower limbs, and normal or slightly diminished sensation. Electrophys iologically, motor nerve conduction velocities were slowed to less than 33 m/s, distal latencies were prolonged, and compound motor action potentials were low. Sensory nerve conduction velocities were extremely reduced or no sensory potentials were recordable. Genetic testing in three affected indiv iduals revealed a duplication of the chromosomal region 17p11.2, In additio n, genetic testing for facioscapulohumeral muscular dystrophy (FSHD) reveal ed a 33 kb EcoRI fragment on chromosome 4q35 in one affected individual and in the clinically normal parent, whereas in a second affected person norma l DNA-sizes were observed, These clinical findings define a new phenotypic variant associated with the Charcot-Marie-Tooth 1A duplication, This may be due to a mutation in another gene contained in the 1.5 Mb duplication alth ough mutations in the peripheral myelin protein 22 gene have been excluded. Alternatively, the genetic background of other genes in the family may mod ify the phenotypic expression, as found in other inherited diseases,The unu sual phenotype cannot be explained by the concomitant presence of FSHD desp ite some evidence for coexistance in one individual. (C) 2000 John Wiley & Sons, Inc.