summary Charcot-Marie-Tooth Disease (CMT), is the most common cause of inherited neuromuscular disease, and encompasses a wide variety of inherited sensorimotor, sensory and/or motor neuropathies. Diagnosis is made with neurophysiologic studies involving the upper and lower extremity (can distinguish between primary or axonal pathology). Clinical exam typically presents with gradual distal extremity weakness and sensory loss in the first two decades of life as well as foot structure deformities (pes cavus, claw toes) due to characteristic muscular imbalances. Treatment involves a multidisciplinary approach to address neuropathy, cavovarus and claw foot deformities, and scoliosis. Epidemiology Incidence 1 in 2500 people global distribution and no ethnic predisposition Etiology Pathophysiology CMT is a heterogenous group of inherited peripheral neuropathies that cause damage to the peripheral nervous system abnormal myelin sheath protein is the basis of this degenerative neuropathy. related disorders include: Distal hereditary motor neuropathy (dHMN- predominant motor neuropathy) and Hereditary sensory/autonomic neuropathy CMT type 1 autosomal dominant 50% of all CMT cases demyelinating form caused by abnormal myelin sheath protein function typically, have slowed nerve conduction velocities (NCV) 1A is caused by a duplication on chromosome 17 on the region containing peripheral myelin protein 22 gene (PMP22) deletion at the PMP22 of the same region on chromosome 17 gene causes Hereditary neuropathy with liability to pressure palsies (HNPP) expressed in schwann cells CMT Type 2 autosomal dominant AR-CMT type 2 is a subtype which occurs in an autosomal recessive axonal pattern comprise around 20% of all CMT cases axonal form with wider age range of onset and variable degree of disability intact myelin sheath with wallerian axonal degeneration generally have normal nerve conduction studies CMT type 4 autosomal recessive demyelinating pattern CMT X x-linked inherited pattern pathoanatomy affected muscles become weak peroneus brevis peroneal involvement is typically first and most profound results in muscle imbalance and varus deformity tibialis anterior weakness results in dropfoot intrinsic muscles of hand and foot check for wasting of 1st dorsal interosseous in hands Genetics inheritance see subtypes above autosomal dominant duplication of chromosome 17 is most common codes for peripheral myelin protein 22 (PMP 22) expressed in Schwann cells (most common) Orthopedic manifestations foot deformity - pes cavovarus claw toes foot drop hip dysplasia scoliosis hand muscle atrophy and weakness Classification CMT is classified according to the pattern of inheritance and neurophysiologic studies the letter designation denotes the identified genetic pathogenic variant (subtype) there are over 130 identified genes, 160 CMT types which divide into 13 classifications CMT1 CMT2 CMT 4 AR-CMT2 CMTX CMT-DI (dominant intermediate) CMT-RI (recessive intermediate) dHMN (Distal hereditary motor neuropathy) dSMA (Distal spinal muscular atrophy) GAN (Giant axonal neuropathy) HMSN (Hereditary motor and sensory neuropathy) HSAN (Hereditary sensory and autonomic neuropathy) HSN (Hereditary sensory neuropathy) Classification of CMT Type I A demyelinating form that slows nerve conduction velocity Characteristics: 1. autosomal dominant 2. onset in first or second decade of life 3. most commonly leads to cavus foot 4. normal life expectancy 5. motor involvement more profound than sensory Type II Direct axonal death caused by Wallerian degeneration (not demyelination) Characteristics: 1. Usually less disabled than Type I 2. onset in second decade of life or later 3. most commonly leads to flaccid foot Presentation Symptoms motor deficits initial symptoms are distal weakness and atrophy of the distal muscles high steppage gait (due to foot drop) tripping and falls chronic ankle instability "inverted champagne bottle" lower extremity atrophy lateral foot pain sensory reduced sensation in lower limbs classically a stocking or glove distribution balance problems due to impaired proprioception Physical exam lower extremity cavovarus foot (similar to Freidreich's ataxia) with hammer toes or clawing of toes usually bilaterally and symmetric. occurs due to unoposed pull of peroneus longus causing plantarflexion of the first ray and compensatory hindfoot varus. initially flexible, but progresses to a rigid deformity motor weakness peroneal weakness weakest muscles around foot and ankle anterior tibialis can lead to drop foot in swing initially and later to a fixed equinus calf atrophy weak intrinsics including weak EDB and EHB claw toes hyporeflexia or areflexia Coleman block test test to determine if hindfoot varus deformity is secondary to plantar-flexed first ray vs an independent component. If deformity corrects with Coleman block, this suggests a forefoot driven varus deformity. If deformity does not correct with Coleman block, this suggests hindfoot driven varus deformity. a rigid hindfoot will not correct into neutral can be difficult to determine until soft tissue balancing completed upper extremity intrinsic wasting of hands weak pinch dexterity and grasp r spared spine scoliosis may be evident on Adam's forward bend test Studies NCS allows for classification of CMT into demyelinating and axonal forms demyelinating forms cutoff for demyelinating motor nerve conduction velocity is 38m/s axonal forms exhibit speeds greater than 45 m/s decreased compound muscle action potential amplitudes (CMAPs) for motor nerves and decreased sensory nerve action potentials (SNAPs) Genetic Testing key component for diagnosis of CMT DNA analysis PCR analysis used to detect peripheral myelin protein 22 (PMP22) gene mutations chromosomal analysis duplication on chromosome 17 seen in autosomal dominant (most common) form Cavus Foot Deformity Introduction evaluation and treatment follows same principals for cavovarus foot pathophysiology cavus caused by peroneus longus overpowering weak tibialis anterior leading to plantar flexed 1st ray weak intrinsics and contracted plantar fascia varus caused by tibialis posterior (normal) overpowering weak peroneus brevis Treatment nonoperative accomodative shoe wear indications mild deformity full-length semi-rigid insole orthotic with a depression for the first ray and a lateral wedge indications flexible cavus foot deformity in adult supramalleolar orthosis (SMO) indications more severe cavovarus deformity recalcitrant to shoe wear accommodations ankle foot orthosis (AFO) indications Integral in the treatment of foot drop to assist with gait and balance works best if equinus is a dynamic defomrity (not rigid) lace-up ankle brace and/or high-top shoe or boots indications may consider in moderate deformities when patient does not tolerate the more rigid bracing with an SMO or AFO operative soft tissue reconstruction indications flexible deformity in adolescents with closed physes failed conservative management of fixed deformities performed with a combination of the following procedures plantar release (plantar fascia +/- Steindler stripping, i.e. release of short flexors off the calcaneus) indications cavus lengthening of gastrocnemius or tendoachilles (TAL) indications ankle equinus outcomes gastrocnemius recession produces less calf weakness and can be combined with plantar release simultaneously posterior tibial tendon transfer indications muscle imbalance: posterior tibialis typically is markedly stronger than evertors and maintains strength through the course of disease in CMT cavovarus feet may consider transfer of posterior tibialis to dorsum of foot if dorsiflexion weakness of anterior tibialis is present peroneus longus to brevis transfer indications plantar flexed first ray rationale decreases plantarflexion force on first ray without weakening eversion 1st metatarsal dorsiflexion osteotomy indications flexible hindfoot cavus deformities (normal Coleman block test and/or passive hindfoot eversion past neutral) lateralizing calcaneal osteotomy or lateral closing-wedge osteotomy and arthrodesis indications performed if deformity does not correct with Coleman block test. soft tissues still require balancing and need to be addressed in the setting of arthrodesis Claw Toes Deformity Introduction ankle dorsiflexion weakness may result in the recruitment of toe extensors for assistance in the setting of intrinsic muscle weakness, increased toe extensor activity can lead to claw toe deformity, which becomes rigid with time Treatment operative Jones procedure (EHL transfer to neck of 1st MT and IP arthrodesis) indications for symptomatic claw toe deformity which has failed non-operative measures technique transfers extensor hallucis longus tendon of the great toe to the metatarsal neck in combination with IP arthrodesis goal is to increase contributions to ankle dorsiflexion and decrease clawing in order to relieve pain and deformity Hip dysplasias Introduction hip dysplasia is sometimes associated with CMT (typically less than 10%) may present during adolescence in ambulatory patients Treatment pelvic osteotomy indications symptomatic hip dysplasia outcomes higher rate of sciatic nerve palsy after surgery Scoliosis Introduction often occurs in children with CMT ( ~ 10-20%) characteristic left thoracic and kyphotic curve distinguish from idiopathic scoliosis Treatment nonoperative bracing indications bracing rarely effective so not typically used operative fusion and instrumentation indications progressive deformity with scoliosis > 50 degrees