HEREDITARY PERIPHERAL NEUROPATHIESA UNIQUE APPROACH TO IMPROVING DIAGNOSTIC YIELD & VALUE IN NEUROPATHY EVALUATION

CMTCharcot-Marie-Tooth

HMSNHereditary Motor & Sensory Neuropathy

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.

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

METABHereditary Metabolic

Neuropathy

HSANHereditary Sensory and Autonomic Neuropathy

HSNHereditary Sensory

Neuropathy

EXTENT OF DISEASE AND OVERLAP

HSPHereditary

Spastic Paraplegia

HMNHereditary

Motor Neuropathy

MEANINGFUL RESULTS THROUGH A MULTI-DISCIPLINARY APPROACH

At Mayo Clinic, we integrate comprehensive genetic testing with a multidisciplinary team of clinical peripheral neuropathy experts, laboratory scientists, and genetic counselors to provide the highest standard for mutation detection.

Our targeted approach allows for optimal mutation detection and interpretation though targeted capture techniques and unique reporting methods. This process eliminates the risk of false negative results compared to whole-exome sequencing and other capture techniques, which provides physicians with the confidence that disease-specific mutations have not been missed.

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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)

HSNP HMSNP HSPP HMNP MSNP

SENSORY MOTOR üAUTONOMIC

HEREDITARY SENSORY & AUTONOMIC NEUROPATHY

HEREDITARY MOTOR & SENSORY NEUROPATHY

HEREDITARY SPASTIC PARAPLEGIA WITH NEUROPATHY

DISTAL HEREDITARY MOTOR NEUROPATHY

METABOLIC OR SYNDROMIC NEUROPATHY

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TESTING FOR THE DIAGNOSIS OF HEREDITARY NEUROPATHIES

MAYO TEST ID TEST NAME TURNAROUND TIME

PNPAN Peripheral Neuropathy Expanded Panel by Next-Generation Sequencing 10 weeks

PMP22 PMP22, Peripheral Neuropathy, FISH (Deletion/Duplication) 7 days

HMSNP Hereditary Motor and Sensory Neuropathy Panel by Next-Generation Sequencing (NGS) 10 weeks

HMNP Hereditary Motor Neuropathy Panel by Next-Generation Sequencing (NGS) 10 weeks

HSNP Hereditary Sensory/Autonomic Neuropathy Panel by Next-Generation Sequencing (NGS) 10 weeks

HSPP Hereditary Spastic Paraplegia Neuropathy Panel by Next-Generation Sequencing (NGS) 10 weeks

MSNP Metabolic or Syndromic Neuropathy Panel by Next-Generation Sequencing (NGS) 10 weeks

COMPREHENSIVE EVALUATION

PHENOTYPE-SPECIFIC EVALUATIONS

MC2775-99rev0417

@mayocliniclabs/mayocliniclabsnews.mayomedicallaboratories.commayomedicallaboratories.com

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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 MATTHEW FERBER, PH.D.2 KEVIN HALLING, M.D., PH.D.3 LINDA HASADSRI, M.D., PH.D.4 W. EDWARD HIGHSMITH, JR., PH.D.5 CRISTIANE IDA, M.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.

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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.