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 login to view 1 more bullet 1A is caused by a duplication on chromosome 17 on the region containing peripheral myelin protein 22 gene (PMP22) login to view 2 more bullets CMT Type 2 autosomal dominant login to view 1 more bullet 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 login to view 1 more bullet CMT type 4 autosomal recessive demyelinating pattern CMT X x-linked inherited pattern pathoanatomy affected muscles become weak peroneus brevis login to view 2 more bullets tibialis anterior login to view 1 more bullet intrinsic muscles of hand and foot login to view 1 more bullet Genetics inheritance see subtypes above autosomal dominant duplication of chromosome 17 is most common login to view 1 more bullet 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 login to view 6 more bullets motor weakness login to view 8 more bullets hyporeflexia or areflexia Coleman block test login to view 5 more bullets upper extremity intrinsic wasting of hands weak pinch login to view 1 more bullet 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 login to view 1 more bullet axonal forms login to view 2 more bullets 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 login to view 2 more bullets varus caused by tibialis posterior (normal) overpowering weak peroneus brevis Treatment nonoperative accomodative shoe wear login to view 2 more bullets full-length semi-rigid insole orthotic with a depression for the first ray and a lateral wedge login to view 2 more bullets supramalleolar orthosis (SMO) login to view 2 more bullets ankle foot orthosis (AFO) login to view 3 more bullets lace-up ankle brace and/or high-top shoe or boots login to view 2 more bullets operative soft tissue reconstruction login to view 21 more bullets 1st metatarsal dorsiflexion osteotomy login to view 2 more bullets lateralizing calcaneal osteotomy or lateral closing-wedge osteotomy and arthrodesis login to view 3 more bullets 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) login to view 5 more bullets 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 login to view 1 more bullet outcomes login to view 1 more bullet Scoliosis Introduction often occurs in children with CMT ( ~ 10-20%) characteristic left thoracic and kyphotic curve distinguish from idiopathic scoliosis Treatment nonoperative bracing login to view 2 more bullets operative fusion and instrumentation login to view 2 more bullets