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Familial Asymmetric Distal Upper Limb Amyotrophy (Hirayama Disease): Report of a Greek Family

Andreadou, Elisabeth MD*; Christodoulou, Kyproula PhD; Manta, Panagiota MD*; Karandreas, Nicos MD*; Loukaidis, Panagiotis MD*; Sfagos, Constantinos MD*; Vassilopoulos, Demetrios MD, PhD*

doi: 10.1097/NRL.0b013e31818d6717
Clinical Report

Introduction: Hirayama disease is a rare nonprogressive, predominantly unilateral, juvenile distal upper limb amyotrophy that involves C7, C8, and Th1 innervated muscles. The etiology and pathogenesis of this focal amyotrophy is presently unknown. There is a debate as to whether Hirayama disease is an unusual neck flexion induced cervical myelopathy or an intrinsic motor neuron disease. Despite being a sporadic disorder, familial forms have been occasionally described, with either autosomal recessive or dominant inheritance.

Case Series: We describe a 3-generation Greek family, with 4 members affected by a benign distal upper limb amyotrophy of long duration, reminiscent of Hirayama disease, suggesting an autosomal dominant inheritance pattern. Hypothesizing that this familial amyotrophy might be related to autosomal dominant distal spinal muscular atrophy type V(dSMA-V) that is characterized by prominent involvement of the distal upper extremities, we tested the index case for glycyl tRNA synthetase and Berardinelli-Seip congenital lipodystrophy (BSCL2) N88S and S90L gene mutations (by direct sequencing) that are involved in the development of dSMA-V phenotype. Despite the phenotypical similarity of this familial amyotrophy to dSMA-V, no missense mutation in the genes presently associated with it was detected.

Conclusion: The reported family is the first in the literature with occurrence of Hirayama amyotrophy in 3 generations of a family. Considering that familial forms of Hirayama amyotrophy are uncommon, it could be assumed that they might represent a different subtype of the same disease having the same clinical features but different pathogenesis.

From the *Department of Neurology, Athens National University, Aeginition Hospital, Athens, Greece; and †Molecular Genetics Department D, Neurogenetics Laboratory, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.

This work was supported in part by the Muscular Dystrophy Association of the United States (grant MDA3401) (to K. C).

Reprints: Elisabeth Andreadou, MD, Department of Neurology, Aeginition Hospital, 74 Vas. Sophia’s Ave., 11528 Athens, Greece. E-mail:

© 2009 Lippincott Williams & Wilkins, Inc.