HEREDITARY PERIPHERAL NEUROPATHIESIMPROVING DIAGNOSTIC YIELD AND VALUE IN NEUROPATHY EVALUATION

N E U R O L O G Y A T M A Y O C L I N I C

M A Y O M E D I C A L L A B O R A T O R I E S . C O M / H P N

WHY SHOULD I ORDER A COMPREHENSIVE EVALUATION?

Hereditary peripheral neuropathies are quite varied in their presentations and even more diverse in terms of their specific genetic causes. While they can sometimes be framed in terms of the extent of weakness, sensory involvement, and/or autonomic involvements, it is difficult to discern the appropriate test for many patients. A comprehensive testing approach with next-generation sequencing has been studied to show greater value in testing, and is therefore recommended.

Furthermore, previous testing approaches required testing a huge list of etiologies for acquired possibilities, while at the same time, trying to guess what individual gene may be most likely responsible. Those methods are extremely challenging, provide a low diagnostic yield, and result in high costs.

A simplified algorithm of evaluations (see insert) can be considered, especially among those younger than 40 years of age or with a family history.

WHAT ARE HEREDITARY PERIPHERAL NEUROPATHIES?Hereditary peripheral neuropathies are a relatively common diverse group of disorders with heterogeneous genetic causes. Due to the considerable overlap in the clinical phenotypes of various neuropathies, it is often difficult to distinguish these specific inherited disorders from sporadic, idiopathic, or acquired forms of neuropathy without genetic testing.

MAJOR CATEGORIES OF HEREDITARY PERIPHERAL NEUROPATHIES

1 Hereditary motor and sensory neuropathy (HMSN), also referred to as Charcot-Marie-Tooth (CMT)

2 Hereditary sensory and autonomic neuropathy (HSAN), or hereditary sensory neuropathy (HSN), if autonomic dysfunction is absent

3 Distal hereditary motor neuropathy (dHMN)

4 Hereditary spastic paraplegia (HSP) with neuropathy (complicated form, also referred to as HSMN type 5)

5 Syndromic or metabolic disorders with diverse organ involvements including nerve, some with available or evolving therapies

CONSULT WITH MAYO CLINIC GENETIC COUNSELORS ABOUT TESTING OPTIONS

Genetic counselors bring real value to proper test utilization by ensuring the most appropriate test has been ordered. On average, Mayo Clinic genetic counselors modify 8% of all reviewed genetic test orders1, reducing health care costs and benefiting patient care.

Mayo Clinic genetic counselors are available to:

} Support the ordering process.

} Provide additional information about testing options.

} Offer results interpretation.

} Assist with case review and coordination.

1. Kotzer KE, Riley JD, Conta JH, et al. Genetic testing utilization and the role of the laboratory genetic counselor. Clin Chim Acta 2014;427:193-195.

CMTCharcot-Marie-Tooth

HMSNHereditary Motor & Sensory Neuropathy

C U S T O M E R S E R V I C E F O R C L I N I C A L S P E C I A L I S T S / 8 5 5 - 5 1 6 - 8 4 0 4

H E R E D I T A R Y P E R I P H E R A L N E U R O P A T H I E S

WHICH TEST SHOULD I ORDER?} Peripheral Neuropathy Expanded Panel by Next-Generation Sequencing (Mayo ID: PNPAN)

USEFUL FOR

} Diagnosis of hereditary peripheral neuropathies with isolated nerve involvement or associated with other organ system or associated with metabolic syndromes with known causal genes.

} Serving as a second-tier test for patients in which previous targeted gene mutation analyses for specific hereditary peripheral neuropathy-related genes were negative.

} Identifying mutations within genes known to be associated with hereditary peripheral neuropathy, allowing for predictive testing of at-risk family members.

ADDITIONAL TESTING USEFUL FOR THE DIAGNOSIS OF HEREDITARY NEUROPATHIES

} PMP22, Peripheral Neuropathy, FISH (Deletion/Duplication) (Mayo ID: PMP22)} Hereditary Motor and Sensory Neuropathy Panel by Next-Generation Sequencing (NGS) (Mayo ID: HMSNP)} Hereditary Motor Neuropathy Panel by Next-Generation Sequencing (NGS) (Mayo ID: HMNP)} Hereditary Sensory/Autonomic Neuropathy Panel by Next-Generation Sequencing (NGS) (Mayo ID: HSNP)} Hereditary Spastic Paraplegia Neuropathy Panel by Next-Generation Sequencing (NGS) (Mayo ID: HSPP)} Metabolic or Syndromic Neuropathy Panel by Next-Generation Sequencing (NGS) (Mayo ID: MSNP)

METABHereditary Metabolic

Neuropathy

HSANHereditary Sensory and Autonomic Neuropathy

HSNHereditary Sensory

Neuropathy

BENEFITS OF A DEFINITIVE DIAGNOSIS

Based on age and family history and specific phenotype, this testing can now be harnessed in an algorithmic approach, to:

} Establish treatment and surveillance options.

} Avoid unnecessary diagnostic procedures.

} Eliminate expensive and unnecessary treatments such as IVIG.

} Provide prognosis and counseling.

} Accurately assess risk for family members.

EXTENT OF DISEASE AND OVERLAP

HSPHereditary

Spastic Paraplegia

HMNHereditary

Motor Neuropathy

MC2775-99rev0316

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16 EXPERTISE AT MAYO CLINIC

Our boardcertified laboratory directors in

collaboration with clinical neurologists and

genetic counselors at Mayo Clinic provide

expertise in molecular genetic testing for

inherited peripheral neuropathies.

FOR MORE INFORMATION ABOUT HEREDITARY PERIPHERAL NEUROPATHIES, VISITMayoMedicalLaboratories.com/HPN

CO-DIRECTORS1 D. BRIAN DAWSON, PH.D.2 MATTHEW FERBER, PH.D.3 KEVIN HALLING, M.D., PH.D.4 LINDA HASADSRI, M.D., PH.D.5 W. EDWARD HIGHSMITH, JR., PH.D.6 SARAH KERR, M.D.7 BENJAMIN KIPP, PH.D.8 ZHIYV NIU, PH.D.9 ANDE RUMILLA, M.D.10 STEPHEN THIBODEAU, PH.D.

CONSULTANT11 CHRISTOPHER KLEIN, M.D.

GENETIC COUNSELORS12 JESSICA BALCOM, M.S., CGC13 MARISSA ELLINGSON, M.S., CGC14 CHRISTY KOELLNER, M.S. CGC15 CARRIE LAHNER, M.S., CGC16 EMILY LAUER, CGC17 ANGELA PICKART, M.S., CGC18 KRISTEN RASMUSSEN, CGC19 ELIZABETH SELNER, M.S., CGC20 BRITTANY THOMAS, M.S., CGC21 LINDSEY WALTMAN, CGC

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