Please Summarise in a Tabular form Various CMTs with Inheritance Age o

Please Summarise in a Tabular form Various CMTs with Inheritance Age of Onset Progression, Associated features and Skeletal abnormalities and Nerve Conduction study findings

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I now have very comprehensive data covering CMT1, CMT2 subtypes, CMT3/DSD, CMT4, and CMTX. I have enough information from Bradley & Daroff's Neurology and Goldman-Cecil to compile a thorough tabular summary. Let me now compose the final answer.

Based on my research from Bradley and Daroff's Neurology in Clinical Practice and Goldman-Cecil Medicine, here is a comprehensive tabular summary of Charcot-Marie-Tooth (CMT) disease types:

Charcot-Marie-Tooth (CMT) Disease - Classification Summary

CMT is the most common inherited neuropathy (prevalence ~1:2500). It is classified by inheritance pattern, electrophysiology, and causative gene. Motor NCVs are the key divider: demyelinating (CMT1) <38 m/s, axonal (CMT2) >38 m/s (near-normal), intermediate (35-45 m/s in CMTX).

Table 1: CMT1 (Demyelinating, Autosomal Dominant)

Subtype	Gene / Locus	Inheritance	Age of Onset	Progression	Associated Features	Skeletal Abnormalities	NCS Findings
CMT1A	PMP22 duplication / 17p11.2	AD	1st-2nd decade	Slowly progressive; most remain ambulatory; rarely wheelchair-bound	Distal leg weakness & wasting ("inverted champagne bottle"), reduced/absent DTRs, distal sensory loss; enlarged peripheral nerves palpable	Pes cavus, hammer toes, claw toes; scoliosis in ~10-26%	Markedly reduced MCV (<38 m/s, often 15-35 m/s); reduced SNAP; prolonged DML; uniform slowing; onion bulb formation on biopsy
CMT1B	MPZ / 1q22-q23	AD	1st-2nd decade (can be late-onset)	Variable - some severe early, some mild late-onset phenotype	Prominent sensory loss; areflexia; thickened nerves; late-onset variant milder	Pes cavus, hammer toes	Severely reduced MCV (similar to CMT1A); some late-onset variants have mildly slow or near-normal NCV
CMT1C	LITAF / 16p13.1	AD	1st-2nd decade	Slowly progressive	Clinically similar to CMT1A; distal weakness and wasting	Pes cavus	Reduced MCV (<38 m/s)
CMT1D	EGR2 / 10q21	AD	Childhood	Can be severe; some overlap with DSD/CMT3 phenotype	Hypomyelination features; some with very slow CVs and early onset	Pes cavus	Very slow MCV (<15-25 m/s in some); severe demyelination pattern
CMT1E	PMP22 point mutation / 17p11.2	AD	1st-2nd decade	Slowly progressive; may overlap with HNPP when deletion	Some with hearing loss; more severe than CMT1A in some	Pes cavus, hammer toes	Reduced MCV; similar to CMT1A
CMT1F	NEFL / 8p21	AD	Childhood-adolescence	Progressive; can be severe	Distal weakness and sensory loss; nerve enlargement	Pes cavus	Reduced MCV; may have variable slowing

Table 2: CMT2 (Axonal, Predominantly Autosomal Dominant)

Subtype	Gene / Locus	Inheritance	Age of Onset	Progression	Associated Features	Skeletal Abnormalities	NCS Findings
CMT2A2 (most common CMT2)	MFN2 / 1p36.22	AD	Early - 1st or 2nd decade; can be later	More severe than CMT1A; earlier disability; often wheelchair-dependent in 20s	Optic atrophy in some; distal weakness and wasting; no nerve enlargement	Pes cavus less prominent; foot deformities less severe than CMT1; planovalgus more common in CMT2 overall	Motor NCV normal or near-normal (>38-45 m/s); reduced CMAP amplitude; reduced/absent SNAPs; no uniform slowing
CMT2B	RAB7 / 3q21.3	AD	2nd decade	Progressive	Prominent sensory loss; foot ulcers and ulcerations; resembles HSN1 but lacks lancinating pain	Foot ulcers; mutilating changes	Near-normal MCV; low SNAP amplitudes; axonal pattern
CMT2C	TRPV4 / 12q24	AD	Variable	Progressive; shortened life expectancy	Vocal cord, intercostal, and diaphragmatic weakness - respiratory involvement; RDS can occur	Variable foot deformity	Axonal NCS pattern; near-normal MCV
CMT2D	GARS / 7p15	AD	Adolescence-adulthood	Progressive	Weakness and atrophy MORE severe in hands than feet (upper limb predominant)	Hand/wrist deformity more than feet	Near-normal MCV; reduced CMAP and SNAP amplitudes
CMT2E/CMT1F	NEFL / 8p21	AD	Childhood	Progressive; some with severe phenotype	Some with giant axons on biopsy; secondary demyelination	Pes cavus	Variable - some slow MCV below 38 m/s ("intermediate"); axonal changes + secondary demyelination
CMT2F	HSPB1 (Hsp27) / 7q11.23	AD	Late onset: 35-60 years	Moderate-severe; slowly progressive	Mild sensory impairment; motor > sensory involvement	Foot deformity mild	Lower limb NCVs moderately slowed; upper limb normal or mildly reduced
CMT2I/CMT2J	MPZ (late-onset variants)	AD	Adult onset (>40 years)	Slowly progressive	Hearing loss, pupillary abnormalities (Adie pupils in some)	Minimal skeletal deformity	Near-normal or mildly reduced NCV; axonal pattern

Table 3: CMTX (X-linked)

Subtype	Gene / Locus	Inheritance	Age of Onset	Progression	Associated Features	Skeletal Abnormalities	NCS Findings
CMTX1 (most common X-linked form; ~10-20% of all CMT)	GJB1 (Cx32, Connexin 32) / Xq13.1	X-linked dominant (females often mildly affected)	Males: 1st-2nd decade; Females: later, milder	Males: moderate-severe; females: mild to asymptomatic	No nerve hypertrophy; CNS involvement possible (white matter changes on MRI in some); males more severely affected	Pes cavus, hammer toes in males; less prominent in females	Males: intermediate MCV (35-45 m/s) - does NOT fit cleanly into CMT1 or CMT2; Females: normal or mildly reduced MCV

Table 4: CMT3 / Dejerine-Sottas Disease (DSD) - Severe Infantile Demyelinating

Type	Gene	Inheritance	Age of Onset	Progression	Associated Features	Skeletal Abnormalities	NCS Findings
CMT3 / DSD	PMP22, MPZ, EGR2 (heterogeneous - de novo or AR mutations)	AR or de novo dominant	Infancy / early childhood (birth to age 3)	Rapidly progressive; severe disability early; many wheelchair-dependent in childhood	Severe hypomyelination; grossly enlarged peripheral nerves; areflexia; cranial nerve involvement possible; ataxia; respiratory compromise in some	Severe scoliosis; hip dislocation; severe foot deformities; joint contractures	Extremely slow MCV (<10 m/s in forearm, often 5-8 m/s); severely reduced or absent SNAPs; marked nerve hypertrophy on biopsy (onion bulbs)

Table 5: CMT4 (Autosomal Recessive Demyelinating)

Subtype	Gene / Locus	Inheritance	Age of Onset	Progression	Associated Features	Skeletal Abnormalities	NCS Findings
CMT4A	GDAP1 / 8q21.11	AR	1st-2nd decade	Rapidly progressive; often wheelchair-dependent	Vocal cord paresis in some; severe demyelination	Pes cavus; foot deformity; scoliosis	Very slow MCV; severe demyelinating pattern
CMT4B1	MTMR2 / 11q22	AR	Infancy-early childhood	Severe; progressive	Nerve hypertrophy; myelin outfoldings on biopsy (distinctive)	Severe foot deformity; scoliosis	Very slow MCV (<10-15 m/s); demyelinating
CMT4B2	SBF2 (MTMR13) / 11p15	AR	Childhood	Severe	Glaucoma (a key distinguishing feature)	Foot deformity	Slow MCV; demyelinating pattern
CMT4C	SH3TC2 / 5q32	AR	Childhood	Progressive	Scoliosis particularly severe and common; cranial nerve involvement in some	Severe scoliosis is hallmark; pes cavus	Slow MCV; demyelinating
CMT4D (HMSNL)	NDRG1 / 8q24	AR	Childhood (Lom Roma population)	Severe	Hearing loss; tongue atrophy	Foot deformity; scoliosis	Very slow MCV; demyelinating
CMT4E	EGR2 / 10q21	AR	Infancy	Severe (congenital hypomyelination overlap)	CNS involvement possible	Severe; contractures	Extremely slow MCV
CMT4F	PRX (Periaxin) / 19q13	AR	Childhood	Progressive	Prominent sensory loss; nerve hypertrophy	Foot deformity; scoliosis	Very slow MCV; severe demyelination
CMT4H	FGD4 (Frabin) / 12p11	AR	Childhood	Progressive	Myelin outfoldings	Foot deformity	Slow MCV; demyelinating
CMT4J	FIG4 / 6q21	AR	Variable	Progressive	May have CNS involvement	Variable	Demyelinating NCS pattern

Summary NCS Classification Table

CMT Group	Motor NCV (Forearm)	CMAP	SNAP	Key Biopsy Finding
CMT1 (demyelinating)	<38 m/s (typically 15-35 m/s)	Reduced amplitude	Reduced/absent	Onion bulb formation; demyelination-remyelination
CMT2 (axonal)	>38-45 m/s (near-normal)	Markedly reduced amplitude	Reduced/absent	Axonal loss, no onion bulbs
CMTX1 (males)	35-45 m/s (intermediate)	Reduced	Reduced	Mixed axonal and demyelinating
CMT3/DSD (severe demyelinating)	<10 m/s (often 5-8 m/s)	Severely reduced or absent	Absent	Massive onion bulbs; markedly thickened nerves
CMT4 (AR demyelinating)	<15-25 m/s	Severely reduced	Absent	Demyelination + specific findings (e.g., myelin outfoldings in CMT4B)

Key Clinical Pearls

CMT1A (PMP22 duplication) accounts for ~50% of all CMT; most common overall
CMTX1 (Cx32 mutation) is the second most common form (~10-20%)
CMT2A (MFN2 mutation) is most common axonal form; notable for optic atrophy and earlier severe disability
Planovalgus foot is more common in CMT2; cavovarus foot predominates in CMT1 and other demyelinating forms
Scoliosis occurs in 10-26% of all CMT; especially severe in CMT4C (SH3TC2)
CMT2C (TRPV4) - watch for respiratory compromise from diaphragm/intercostal weakness
CMT4B2 - glaucoma is a distinguishing associated feature
CMT4D - hearing loss in the Lom Roma population is characteristic

Sources: Bradley and Daroff's Neurology in Clinical Practice, Table 106.6 and Ch. 106; Goldman-Cecil Medicine, Ch. 388

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