Management of Charcot–Marie–Tooth disease: improving long-term care with a multidisciplinary approach

Figures & data

Table 1 Overview of CMT clinical type and genetic subtypes

Type	Pathology/phenotype	Inheritance	% of CMT	Subtype and gene
CMT1	– Myelin abnormalities	AD	50–80	CMT1A	PMP22
	– Distal weakness, atrophy, and sensory loss			CMT1B	MPZ
				CMT1C	LITAF
	– Onset: ~5–~20 years			CMT1D	EGR2
	– Motor NCV <38 m/s			CMT1E	PMP22
				CMT1F/2E	NEFL
CMT2	– Axonal degeneration	AD	10–15	CMT2A	MFN2
	– Distal weakness and atrophy, variable sensory involvement			CMT2B	RAB7A
				CMT2C	TRPV4
	– Complicated and severe			CMT2D	GARS
	cases described			CMT2E/1F	NEFL
	– Motor NCV >38 m/s			CMT2F	HSPB1
	– Onset: variable			CMT2G	12q12-q13
				CMT2H/2K	GDAP1
				CMT2I/2J	MPZ
				CMT2L	HSPB8
				CMT2N	AARS
				CMT2M	DMN
				CMT2O	DYNC1H1
				CMT2P	LRSAM1
				CMT2S	IGHMBP2
				CMT2T	DNAJB2
				CMT2U	MARS
Intermediate form	– Myelinopathy and axonal	AD	<4	DI-CMTA	Unknown
	– Motor NCV >25 m/s and <38 m/s			DI-CMTB	DNM2
				DI-CMTC	YARS
				DI-CMTD	MPZ
				DI-CMTF	GNB4
CMT4	– Demyelinating	AR	Rare	CMT4A	GDAP1
	– Recessive			CMT4B1	MTMR2
	– V ariable presentations/phenotypes			CMT4B2	SBF2
				CMT4B3	SBF1
				CMT4C	SH3TC2
				CMT4D	NDRG1
				CMT4E	EGR2
				CMT4F	PRX
				CMT4G	HK1
				CMT4H	FGD4
				CMT4J	FIG4
				CMT2B1	LMNA
				CMT2B2	MED25
CMTX	– Axonal degeneration with myelin abnormalities	XL	10–15	CMTX1	GJB1
				CMTX2	Xp22.2
				CMTX3	Unknown
				CMTX4	AIFM1
				CMTX5	PRPS1
				CMTX6	PDK3

Abbreviations: CMT, Charcot–Marie–Tooth; NCV, nerve conduction velocity; AR, autosomal recessive; AD, autosomal dominant; XL, X-linked.

Figure 1 Flow of multidisciplinary care in diagnosis and management of CMT.

Notes: ^aA simplification of published strategies of genetic testing in CMT as described by Saporta et al¹⁰⁶ and Miller et al.¹⁰⁷ The order of genetic testing (1, 2, 3) is guided by electrodiagnostic findings and inheritance pattern. Please refer to Saporta et al¹⁰⁶ and Miller et al¹⁰⁷ for more detailed recommendations on strategies of cost conscious sequential genetic testing.
Abbreviations: CMT, Charcot–Marie–Tooth; dup, duplication; NCS, nerve conduction studies; EMG, electromyography; MDA, Muscular Dystrophy Association; AD, autosomal dominant; AR, autosomal recessive.

Table 2 Multidisciplinary members and roles in the diagnosis and management of CMT

Neurologist	• Evaluation and diagnosis • Prognostication • Consideration for research studies • Referrals to genetic counselors, PT/OT, mental health • Longitudinal care and reevaluation • Counseling on medications to avoid • Surveillance of comorbidities • Lifestyle modifications to limit disability
Genetic counselor and social worker	• Guidance in clinical- and research-based genetic testing • Ensuring ADA and GINA compliance • Discussion of family testing • Reproductive counseling • Referral to CMT Association and other community organization
Physical and occupational therapist/physiatrist	• E valuation of upper and lower extremity disability • Prescription for ankle–foot orthotics • Recommendations for therapeutic exercise, stretching, balance and postural stabilization, fall risk prevention strategies • Recommendation on exercise, lifestyle modification to limit disability
Psychologist/psychiatrist	• Evaluation and treatment of anxiety, depression, and other psychosocial impact of diagnosis, such as body image
Orthopedic surgeon	• Evaluation and treatment of severe foot, ankle, hip, and spine deformities

Abbreviations: CMT, Charcot–Marie–Tooth; ADA, Americans with Disabilities Act; GINA, Genetic Information Nondiscrimination Act of 2008; PT, physical therapist; OT, occupational therapist.

SaportaASDSottileSLMillerLJFeelySMESiskindCEShyMECharcot-Marie-Tooth disease subtypes and genetic testing strategiesAnn Neurol2011691223321280073

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MillerLJSaportaASDSottileSLSiskindCEFeelySMEShyMEStrategy for genetic testing in Charcot-Marie-diseaseActa Myol201130210911622106713

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