Autosomal dominant distal hereditary motor neuropathy type II: a Korean family without sequence variation in HSPB1 and HSPB8

Distal hereditary motor neuropathy (dHMN) is a heterogeneous group of disorders characterized by weakness and wasting of distal limb muscles without overt sensory abnormalities. Recently, autosomal dominant dHMN has been mapped to chromosome 12q24 and 7q11-q21. We present a family with autosomal dominant adult onset dHMN type II consisting of fi ve affected individuals spanning three generations. They developed mild symmetrical distal lower limb weakness, muscle wasting, and severe foot deformity after the third decade. Genetic analysis showed no support for linkage to chromosome 12q24 and 7q11-q21 in our family. These fi ndings further demonstrate a genetic heterogeneity within dHMN type II. Neurology Asia 2012; 17(3) : 235 – 237 Address correspondence to: Sang-Soo Lee MD, Department of Neurology, Chungbuk National University College of Medicine, 52 Naesudong-ro, Cheongjusi, Chungbuk, 361-711, Korea. Phone: 82-43-269-6336, Fax: 82-43-275-7591, E-mail: [email protected] INTRODUCTION Distal hereditary motor neuropathy (dHMN), also called the spinal type of Charcot-MarieTooth disease or distal spinal muscular atrophy, represents a rare and exclusive motor neuropathy of clinically and genetically heterogeneous conditions caused by degeneration of motor neurons leading to distal muscle weakness and muscle wasting. A classifi cation in seven types based upon mode of inheritance, age at onset, and prevalent involvement of upper or lower limbs has been made. Out of seven types, dHMN type IIA is caused by mutation in the gene encoding heatshock 22-kD protein-8 (HSPB8) on chromosome 12q24 and type IIB is caused by mutation in the gene encoding heat-shock 27-kD protein-1 (HSPB1) on chromosome 7q11-q21. We report a Korean family with autosomal dominant dHMN type II in which the disease started after the age of 20 years. Gene testing had excluded mutation in HSPB1, HSPB8 and superoxide dismutase genes.