AANEM PRACTICE PARAMETER ABSTRACT: Distal symmetric polyneuropathy (DSP) is the most common variety of neuropathy. Since the evaluation of this disorder is not standard- ized, the available literature was reviewed to provide evidence-based guide- lines regarding the role of laboratory and genetic tests for the assessment of DSP. A literature review using MEDLINE, EMBASE, Science Citation Index, and Current Contents was performed to identify the best evidence regarding the evaluation of polyneuropathy published between 1980 and March 2007. Articles were classified according to a four-tiered level of evidence scheme and recommendations were based on the level of evidence. (1) Screening laboratory tests may be considered for all patients with polyneuropathy (Level C). Those tests that provide the highest yield of abnormality are blood glucose, serum B 12 with metabolites (methylmalonic acid with or without homocysteine), and serum protein immunofixation electrophoresis (Level C). If there is no definite evidence of diabetes mellitus by routine testing of blood glucose, testing for impaired glucose tolerance may be considered in distal symmetric sensory polyneuropathy (Level C). (2) Genetic testing is established as useful for the accurate diagnosis and classification of hered- itary neuropathies (Level A). Genetic testing may be considered in patients with cryptogenic polyneuropathy who exhibit a hereditary neuropathy phe- notype (Level C). Initial genetic testing should be guided by the clinical phenotype, inheritance pattern, and electrodiagnostic (EDX) features and should focus on the most common abnormalities, which are CMT1A dupli- cation/HNPP deletion, Cx32 (GJB1), and MFN2 mutation screening. There is insufficient evidence to determine the usefulness of routine genetic testing in patients with cryptogenic polyneuropathy who do not exhibit a hereditary neuropathy phenotype (Level U). Muscle Nerve 39: 116 –125, 2009 EVALUATION OF DISTAL SYMMETRIC POLYNEUROPATHY: THE ROLE OF LABORATORY AND GENETIC TESTING (AN EVIDENCE-BASED REVIEW) J.D. ENGLAND, MD, 1 G.S. GRONSETH, MD, 2 G. FRANKLIN, MD, 3 G.T. CARTER, MD, 4 L.J. KINSELLA, MD, 5 J.A. COHEN, MD, 6 A.K. ASBURY, MD, 7 K. SZIGETI, MD, PHD, 8 J.R. LUPSKI, MD, PHD, 9 N. LATOV, MD, 10 R.A. LEWIS, MD, 11 P.A. LOW, MD, 12 M.A. FISHER, MD, 13 D. HERRMANN, MD, 14 J.F. HOWARD, MD, 15 G. LAURIA, MD, 16 R.G. MILLER, MD, 17 M. POLYDEFKIS, MD, 18 A.J. SUMNER, MD 19 Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation 1 Louisiana State University Health Sciences Center, Baton Rouge, Louisiana, USA 2 University of Kansas, Lawrence, Kansas, USA 3 University of Washington, Seattle, Washington, USA 4 Providence Health System, Southwest Washington, Seattle, Washington, USA 5 Tenet-Forest Park Hospital, St. Louis, Missouri, USA 6 Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, USA 7 University of Pennsylvania Hospital, Philadelphia, Pennsylvania, USA 8 Baylor College of Medicine, Houston, Texas, USA 9 Baylor College of Medicine, Houston, Texas, USA Abbreviations: AAN, American Academy of Neurology; AANEM, American Academy of Neuromuscular and Electrodiagnostic Medicine; AAPM&R, American Academy of Physical Medicine and Rehabilitation; CMT, Charcot–Marie–Tooth; CPG, clinical practice guideline; CSF, cerebrospinal fluid; DSP, distal symmetric polyneuropathy; EDX, electrodiagnostic; GTT, glucose tolerance testing; immunofixation electrophoresis; QSS, Quality Standards Subcommittee; SPEP, serum protein electrophoresis Key words: prospective studies; evaluation; distal symmetric polyneuropathy Correspondence to: American Association of Neuromuscular & Electrodiagnostic Medicine, 2621 Superior Drive NW, Rochester, MN 55901; e-mail: aanem@aanem.org © 2008 Wiley Periodicals, Inc. Published online 15 December 2008 in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mus.21226 116 AANEM Practice Parameter MUSCLE & NERVE January 2009