Charcot-Marie-Tooth Disease (Hereditary Motor Sensory Neuropathy)

Overview

Charcot-Marie-Tooth (CMT) disease or hereditary motor sensory neuropathy (HMSN) is a group of disorders characterized by chronic motor and sensory neuropathy that affect the longest nerves first. Signs/symptoms appear in the lower extremities and, in some cases, the upper extremities. CMT is usually inherited, although it may appear spontaneously due to a new mutation without any family history. The broad types of CMT are based on whether the neuropathy is due to demyelination/dysmyelination (type 1) or abnormalities in the axons (type 2). Mixed forms are common, though, and there are many secondary divisions (based on type of inheritance, such as autosomal or X-linked, dominant or recessive) or by genetic mutation, making the nomenclature confusing. Many “named” types of CMT, e.g., Dejerine-Sottas, represent a clinical phenotype and do not correlate with type (1 or 2), inheritance pattern, or even the specific gene involved.

Beginning in the first or second decades of life, individuals with CMT present with symmetric, slowly progressive distal motor neuropathy of the legs and arms leading to weakness and atrophy of the distal muscles of the legs and hands. Individuals with CMT often have markedly depressed deep tendon reflexes, weak ankle dorsiflexion, and high arched feet (pes cavus). Sensory loss is common and can easily be demonstrated by loss of vibratory sensation. In patients with sensory changes, pain can be a significant contributor to disability. There also can be an associated sensorineural hearing loss. Individuals with CMT may have scoliosis and/or hip dysplasia, but in almost all cases, CMT does not affect cognitive function or life expectancy.

Other Names & Coding

Dejerine-Sottas
Hereditary motor sensory neuropathy, types I-IV
Hereditary neuropathy of infancy
Peroneal muscular atrophy (axonal type)
Roussy-Levy syndrome
ICD-10 coding

G60.0, Hereditary motor and sensory neuropathy

Prevalence

CMT is the most commonly inherited neuropathy. Due to a large number of causative genes and historically poor access to genetic testing, prevalence is poorly understood. With increasing access to genetic testing, this is expected to change. In a review article in 2016, CMT due to demyelination/dysmyelination (type 1) was found to be more common than CMT of the axonal type (type 2). CMT1A due to duplication of the PMP22 gene is the most common form of CMT, accounting for as much as 2/3 of CMT1 cases, with a prevalence of 6.9 per 100 000. [Theadom: 2019] CMT prevalence is approximately 15.7/100,000 . [Barreto: 2016] [Theadom: 2019]

Genetics

More than 80 different genes are associated with CMT, but most are very rare. In demyelinating forms of CMT (CMT1), PMP22 duplication/deletion accounts for as many as 2/3 of cases with GJB1 or MPZ mutations accounting for a large proportion of the remaining cases. In axonal forms of CMT (CMT2), mutations in GJB1, MFN2, and MPZ are by far the most common causes. Notably, with the emergence of genetic testing, disorders that were once thought to be distinctly demyelinating (CMT1) or axonal (CMT2) have shown significant overlap (see CMT and Related Disorders (Gene Reviews)). GJB1, an X-linked gene coding for the connexin-32 protein, is a notable example of this phenotypic heterogeneity with both axonal and demyelinating forms of CMT and X-linked inheritance that can affect both males and females. In addition, patients with GJB1-related disorders can have central demyelination, including MRI changes and stroke-like episodes in response to stressors, such as fever (see GJB1 Disorders: Charcot Marie Tooth Neuropathy (CMT1X) and Central Nervous System Phenotypes (Gene Reviews)). GDAP1-related motor and sensory neuropathy is usually axonal and usually recessive, but the demyelinating type and an autosomal dominant form are sometimes present. [Bird: 1993]

CMT1 involves autosomal dominant conditions with a primary effect on myelination of peripheral nerves. There are 3 main types of CMT1 with the most common (CMT1A) reflecting duplication of a 1.5Mb segment of chromosome 17p11 and subsequent overexpression of the PMP22 gene. [van: 2014] PMP22 codes for peripheral myelin protein 22, a protein that is important to myelin sheath function. A deletion in the PMP22 causes a separate neuromuscular condition, hereditary neuropathy with predisposition to pressure palsy (HNPP). Importantly, patients with deletion of duplication or deletion of PMP22 may have larger deletions encompassing additional genes and complicating the phenotype. In cases complicated by multiple affected systems or cognitive delays, consider additional testing, such as a microarray study to fully define the deletion/duplication. CMT1B is also autosomal dominant with mutations in the MPZ gene, coding for the myelin protein zero. Mutations in LITAF, EGR2, and NEFL genes cause CMT1C, CMT1D, and CMT1E, respectively.

CMT 2 is less common than CMT1 and results from abnormalities in axons of peripheral nerves with normal myelin. The most common form, CMT2A, is due to a mutation in the MFN2 gene responsible for the production of Mitofusin2, a protein associated with mitochondrial fusion. Other genes that have been associated with CMT2 include RAB7 (CMT2B), GARS (CMT2D), NEFL (CMT23) HSP27 (CMT2H), and HSP22 (CMP2I).

CMT3, also called Dejerine Sottas disease, is a severe demyelinating neuropathy beginning in infancy – a phenotypic description. Although other genes may be associated with it, specific point mutations in the MPZ and PMP22 are found most often.

CMT4 refers to a group of autosomal recessive demyelinating motor and sensory neuropathies, many of which are very rare and may only be found in a small number of people or certain ethnic populations due to founder effects. CMT4 may be associated with leg weakness in childhood with a fast progression to inability to walk in adolescence.

CMTX is X-linked and due to point mutations in the GJB1 gene encoding connexin-32, a protein made by the Schwann cells that are responsible for producing the myelin sheath. These patients may have transient stroke-like symptoms and abnormal MRIs. [Wang: 2016]

Prognosis

Children with a family history and the few with more severe forms of CMT are likely to be diagnosed early in life. However, in most cases, CMT causes slowly progressive motor and sensory symptoms that lead to diagnosis during adolescence. Since proximal strength is relatively preserved and progression is slow, affected individuals rarely lose ambulation; some will need a wheelchair later in adulthood. In most cases, CMT does not shorten life expectancy. Peripheral neuropathy is a common finding in many neurodegenerative disorders; systemic findings should prompt a broader evaluation for them. Orthopedic issues are the most significant medical problem faced by those with CMT and may include ankle and foot contractures and pes cavus, dislocated or dysplastic hips, and scoliosis.

Practice Guidelines

There are no formal published practice guidelines for CMT, but a multidisciplinary approach to care is most beneficial and care guidelines are beginning to emerge. [McCorquodale: 2016] [Corrado: 2016]

Roles of the Medical Home

The medical home should monitor for associated problems (scoliosis, hip problems, foot abnormalities, and hand and leg weakness) and refer to orthopedics, occupational and physical therapy, and orthotists as necessary. Children and adolescents with CMT will often have problems with physical education and handwriting/key-boarding. A 504 letter requesting accommodations at school may be helpful.

Clinical Assessment

Overview

Before diagnosis, primary care clinicians should be aware of CMT as an underlying etiology for scoliosis, abnormal feet, hip problems, and problems with fine motor abilities. If suspected, nerve conduction velocities/electromyography (NCV/EMG) testing confirms the diagnosis and differentiates between type 1 (demyelinating) and type 2 (axonal). Genetic testing then confirms genetic subtype of CMT, inheritance pattern, more detail about prognosis, and allows family members to be tested.

Pearls & Alerts for Assessment

Toe-walking

Toe-walking may be idiopathic or due to brain, spinal cord, or nerve abnormalities. CMT is one of the causes that should be considered, especially in the absence of other systemic findings.

Individuals with CMT may present in a variety of ways

Attention to the possibility of an underlying neuropathy should be given in those with toe-walking, cavovarus feet, flat feet, or foot drop (due to weakness in ankle dorsiflexion), problems with balance, hip dysplasia, or scoliosis.

Screening

Of Family Members

If a child has CMT, consider genetic screening of the family, particularly if there is a family history of CMT. When the genetic type of CMT is known for the child, this test is low cost or often covered at no cost by the laboratory that conducted the original testing for the child.

For Complications

In individuals with CMT, consider screening infants/toddlers for hip dysplasia and school-age children/adolescents for scoliosis. If present, individuals should be referred to orthopedics for management.

Diagnostic Criteria

CMT is diagnosed in individuals with a clinical presentation, including toe-walking or foot abnormalities, decreased reflexes and/or vibratory sensation, and distal lower extremity weakness. NCV/EMG testing confirms involvement of peripheral nerves showing motor and sensory nerve changes and localizes the problem to abnormal myelination (type 1) or problems with the axons themselves (type 2). The diagnosis is then confirmed by genetic testing, which can be done in large gene panels.

Parents may already know if they have type 1 (demyelinating), type 2 (axonal), and their subtype, making genetic testing for the child easier and less expensive since the NCV/EMG step can be skipped.

Clinical Classification

CMT is broadly classified into 2 types: CMT1, which is due to abnormal myelin formation along the peripheral nerves, and CMT2, which is due to abnormal axons. CMT2 is less common than CMT1. See the Genetics section for more detail.

Differential Diagnosis

CIDP or chronic inflammatory demyelinating polyneuropathy is an immune-mediated disease in which inflammatory changes damage peripheral nerves and their myelin coverings. Both motor and sensory nerves may be affected. This condition is subacute, occurring over at least 2 months, and not congenital or inherited. It tends to involve proximal as well as distal muscles (it is not length dependent) and is more often found in adults. It can be hard to diagnose, though NCV/EMG testing will show slow conduction velocities, CSF will usually show a high protein, and MRI imaging of the nerve roots will show enlarged nerves and possibly nerve root enhancement.

Distal myopathies: In most muscle disorders (myopathies and muscular dystrophies), weakness is proximal, involving shoulders and hips; in most neuropathic disorders such as CMT, muscle weakness is distal, involving hands and feet. However, there are many exceptions, including a variety of distal myopathies. Mutation in dysferlin (DYSF), caveloin3 (CAV3), desmin (DES), and titin (TTN) are relatively common distal myopathies that should be considered, especially if genetic testing for CMT is normal or NCS/EMG is not clearly neuropathic.

Metabolic and neurodegenerative disorders: Since myelin is largely composed of lipids, any disruption of lipid metabolism can cause abnormal myelin formation, either centrally, peripherally, or both. Leukodystrophies such as X-linked adrenoleukodystrophy, infantile neuroaxonal dystrophy, and peroxisomal disorders (Refsum disease, Zellweger syndrome) and others often include peripheral neuropathy in addition to central demyelination. Friedreich’s ataxia (FA) is a relatively common degenerative condition that begins with gait abnormalities due to distal weakness in childhood or adolescence. Ataxia and peripheral neuropathy are prominent findings. Patients with FA can also have prominent cardiomyopathy.

Medical Conditions Causing Condition

Some chemotherapy agents, such as vincristine, may cause peripheral neuropathy. Significantly, patients with CMT exposed to chemotherapy agents can have rapid progression of their neuropathy and dramatic loss of function over a short period.

History & Examination

Current & Past Medical History

Inquire about past problems with foot/muscle pain, balance, a delay in walking, foot surgeries, etc.

Family History

There is often a family history of CMT; depending on the responsible mutation, the inheritance pattern will be autosomal dominant or recessive or X-linked. This history may not be well-known to the family and may need to be explored with questions such as early wheelchair use, use of orthotics, difficulty walking, etc. Variable severity, even among family members with the same mutation, is common.

Pregnancy/Perinatal History

There are no effects on pregnancy/perinatal history.

Developmental & Educational Progress

Ask about problems in school with fine motor abilities, such as hand-writing, using scissors, etc. and problems keeping up with other children during recess and physical education.

Physical Exam

Ask about muscle cramps, pain in hands or feet, frequently sprained ankles, fatigue.

Growth Parameters

Monitor weight for obesity. It is best to discuss this early and prevent it from happening since it can further stress walking and other activities. See Childhood Obesity Screening & Prevention.

Chest

Look for scoliosis.

Extremities/Musculoskeletal

Look for deformities of the feet and muscle loss in feet and hands.

Neurologic Exam

Deep tendon reflexes are usually absent or decreased (proximal <distal). Heel cords may be tight. The child might toe-walk and have cavo-varus feet or pes cavus. The child may have foot drop when walking, which may be described as “foot-slap” by the parents. Vibratory sensation is usually reduced in the lower extremities. Although more difficult to detect clinically, sensation may also be reduced in the feet. The patient/family should do visual checks for sores or bruising every night.

Testing

Sensory Testing

Sensorineural hearing loss is described in some individuals with CMT and should be screened for if there are concerns about hearing. See Hearing Screening.

Genetic Testing

CMT/hereditary motor sensory neuropathy panels are available commercially. They first test for the most common mutation in the gene coding for the PMP22 protein, and, if negative, reflexes to test for other known CMT-associated gene mutations. Occasionally, whole-exome sequencing is necessary.

Other Testing

If CMT is suspected clinically, but there is no family history to guide testing, Nerve conduction velocity/electromyography (NCV/EMG) testing is first done to confirm the diagnosis and determine whether it is demyelinating vs. axonal. This confirms the diagnosis of neuropathy; it can guide genetic testing for type 1 or type 2 and make testing less expensive and more likely to be approved by insurance. NCV/EMG can be skipped if parents know their type or subtype.

Sometimes a motion analysis lab or a gait lab test is performed to determine patterns of walking and inform decisions by physical therapists/orthopedic physicians regarding casting vs. bracing vs. surgery.

Specialty Collaborations & Other Services

Pediatric Neurology (see NM providers [31])

Children with suspected CMT should be evaluated by a pediatric neurologist or preferably, a neuromuscular clinic. Neuromuscular Clinics are multidisciplinary clinics for evaluation, diagnosis, and management of children with CMT. In addition to neurologists specializing in neuromuscular disorders, other disciplines, such as orthotics, occupational therapy, physical therapy and others depending on local expertise are available.

Occupational Therapy (see NM providers [298])

Children with CMT with difficulties in hand use, such as hand-writing, buttoning, etc., should be referred to occupational therapy.

Physical Therapy (see NM providers [321])

Children with CMT with abnormal gait, abnormal feet, balance difficulties should be referred to physical therapy. Depending on local expertise, physical therapists may be available at the Neuromuscular Clinic and may suggest orthotics and similar devices.

Pediatric Orthopedics (see NM providers [13])

Children with CMT should be followed by Pediatric Orthopedics for the management of toe-walking and cavo-varus and similar foot abnormalities, as well as providing screening for hip dysplasia and scoliosis.

Prosthetics/Orthotics/Seating (see NM providers [135])

Orthotics may be helpful in children with CMT for preventing toe-walking, stretching of a tight Achilles heel, and to support the ankle in children with foot drop.

Treatment & Management

Overview

Although many symptoms of CMT can be managed, there is currently no treatment for CMT. Patients with CMT should ideally be followed in a multidisciplinary Neuromuscular Clinic to facilitate this management. While there are no FDA-approved medications for CMT, several gene replacement and gene manipulation therapies are under development and are expected to begin clinical trials in the next few years; no trials are open for children at this time, but this is expected to change rapidly.

Pearls & Alerts for Treatment & Management

Orthotics and braces

Many children/adolescents with CMT are prescribed ankle foot braces/orthotics but don’t like to/will not wear them. In patients with milder weakness, good footwear including high-topped shoes and solid ankle support may be almost as helpful and may be more likely to be worn.

Pain

Patients with CMT may have a lot of foot and muscle pain that may be debilitating, especially if there is a large sensory component to the neuropathy. Cognitive behavioral therapy and/or preventive medications, such as gabapentin, may be helpful.

How should common problems be managed differently in children with Charcot-Marie-Tooth Disease (Hereditary Motor Sensory Neuropathy)?

Prescription Medications

Some medications can be neurotoxic and should be avoided in individuals with CMT (see Neurotoxic Medications (CMT Association)). Most of these are not widely used in children but should be avoided if possible. Chemotherapeutics agents (vincristine and others), pyridoxine (vitamin B6), and some antibiotics (fluoroquinolones and nitrofurantoin) are the most common that might come up in a pediatric practice. As with any medication, the risk of the medication has to be weighed with the benefits.

Systems

Neurology

There are currently no specific treatments for CMT, but this is likely to change in the next few years with development of genetic therapies, which are going through pre-clinical validation and, in some cases, in clinical trials in adults. In the meantime, individuals with CMT should be managed in a specific neuromuscular clinic, such as those run by the MDA (see Find Your MDA Clinics (MDA.org)) or other dedicated neuromuscular clinic. Such multidisciplinary clinics will also have access to clinical trials when they become available.

New or increasing neurologic symptoms, such as pain, should be monitored for and treated as necessary. Gabapentin is usually the first choice in the control of chronic pain in children and adolescents. Also see Pain in Children with Special Health Care Needs.

Degree of disability should also be monitored, especially in walking/running and using hands. Although there is no specific natural history study to cite, the feeling among neuromuscular clinicians is that a decline in abilities is often noted during and after growth spurts. Assistive devices such as braces, orthotics, wheelchairs, specialized utensils, and writing implements should be prescribed when necessary with input from physical and occupational therapists.

A multidisciplinary clinic will have access to physical therapy and occupational therapy to maximize walking and fine-motor function with exercise or the use of orthotics or adaptive aids for daily living, such as larger, easier to grasp pens and eating utensils. School performance, particularly physical education and fine motor skills should also be monitored and a 504-accommodation letter provided as needed. See Sample Letter Requesting a 504 Plan for Charcot-Marie-Tooth (Medical Home Portal) (PDF Document 96 KB).

Specialty Collaborations & Other Services

Neuromuscular Clinics (see NM providers [2])

Although each clinic varies, multidisciplinary clinics can have pediatric neurology, genetics/genetic counseling, orthopedics, etc. If possible, children should be referred to a Neuromuscular Clinic if CMT is suspected for diagnosis and management. Genetic counseling is usually available and testing of other family members may be possible.

Pediatric Neurology (see NM providers [31])

If a Neuromuscular Clinic is not available, children/adolescents with CMT should be referred to pediatric neurology if the diagnosis is suspected.

Musculoskeletal

Children and adolescents should be followed by an orthopedist experienced with neuromuscular disorders in children. Spine, hips, feet, and hands should be monitored for changes over time with physical examination, X-rays, or other imaging when needed. Bracing and casting to help keep or improve range of motion may be used in younger children, although surgery may be needed in older children and adolescents. Though there is no evidence that botulinum toxin injections help to preserve range of motion, these may still be tried in some individuals but are generally avoided in patients with neuromuscular conditions [Burns: 2010]. In older children and adolescents, high-topped shoes and/or ankle foot orthotics may be prescribed to help with foot drop/foot slap, which causes an abnormal gait and frequent tripping.

Specialty Collaborations & Other Services

Pediatric Orthopedics (see NM providers [13])

Children/adolescents with CMT should be followed by pediatric orthopedics for management of foot deformities, hip dysplasia, scoliosis as needed if not available in the local Neuromuscular Clinic.

Ask the Specialist

One of my adolescent patients with CMT and abnormal feet is going to a podiatrist who plans a fairly invasive surgery. Is this necessary?

Surgeries on children/adolescents with CMT are complex, both the decision to do surgery and the various issues of CMT as individuals with CMT may not respond in the same way as a person without CMT and nerves may be more sensitive to damage during an operation. A visit to an orthopedic surgeon specializing in neuromuscular conditions may be helpful.

Resources for Clinicians

On the Web

Charcot-Marie-Tooth Hereditary Neuropathy Overview (GeneReviews)
Written to increase the awareness of clinicians regarding Charcot-Marie-Tooth (CMT) hereditary neuropathy, its causes, and management.

Helpful Articles

Miller LJ, Saporta AS, Sottile SL, Siskind CE, Feely SM, Shy ME.
Strategy for genetic testing in Charcot-Marie-disease.
Acta Myol. 2011;30(2):109-16. PubMed abstract / Full Text

Murphy SM, Laura M, Fawcett K, Pandraud A, Liu YT, Davidson GL, Rossor AM, Polke JM, Castleman V, Manji H, Lunn MP, Bull K, Ramdharry G, Davis M, Blake JC, Houlden H, Reilly MM.
Charcot-Marie-Tooth disease: frequency of genetic subtypes and guidelines for genetic testing.
J Neurol Neurosurg Psychiatry. 2012;83(7):706-10. PubMed abstract / Full Text

Clinical Tools

Letters of Medical Necessity

Sample Letter Requesting a 504 Plan for Charcot-Marie-Tooth (Medical Home Portal) (PDF Document 96 KB)
A sample of a short letter requesting that school personnel allow the child to self-monitor physical activity, and allow the child extra time for timed tests.

Medication Guides

Neurotoxic Medications (CMT Association)
A list of medications that should be avoided for patients with CMT, even those that are fairly asymptomatic.

Resources for Patients & Families

Information on the Web

Charcot-Marie-Tooth Association
A non-profit organization focused on research into treatments for CMT and information for patients and families.

Charcot-Marie-Tooth Disease Fact Sheet (NINDS)
Authoritative answers to common questions about Charcot-Marie-Tooth disease, including what research is being done and additional sources of information; National Institute of Neurological Disorders and Stroke.

National & Local Support

Find Your MDA Clinics (MDA.org)
On the MuscularDystrophyAssociation.org site, will find local muscular dystrophy clinics by zip code.

Muscular Dystrophy Association
A nonprofit health agency dedicated to curing muscular dystrophy, ALS, and related diseases by funding worldwide research.

Studies/Registries

Clinical Trials in Charcot-Marie-Tooth (clinicaltrials.gov)
List of current clinical trials in Charcot-Marie-Tooth disease; a service of the U.S. National Institutes of Health.

Services for Patients & Families in New Mexico (NM)

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.

Authors & Reviewers

Initial publication: October 2020
Current Authors and Reviewers:
Authors: Lynne M. Kerr, MD, PhD
Tara M. Newcomb, CGC, MS
Reviewer: Russell Butterfield, MD, Ph.D.

Bibliography

Barreto LC, Oliveira FS, Nunes PS, de França Costa IM, Garcez CA, Goes GM, Neves EL, de Souza Siqueira Quintans J, de Souza Araújo AA.
Epidemiologic Study of Charcot-Marie-Tooth Disease: A Systematic Review.
Neuroepidemiology. 2016;46(3):157-65. PubMed abstract

Bird TD.
GDAP1-Related Hereditary Motor and Sensory Neuropathy.
Gene Reviews. 1993. PubMed abstract

Burns J, Scheinberg A, Ryan MM, Rose KJ, Ouvrier RA.
Randomized trial of botulinum toxin to prevent pes cavus progression in pediatric Charcot-Marie-Tooth disease type 1A.
Muscle Nerve. 2010;42(2):262-7. PubMed abstract

Corrado B, Ciardi G, Bargigli C.
Rehabilitation Management of the Charcot-Marie-Tooth Syndrome: A Systematic Review of the Literature.
Medicine (Baltimore). 2016;95(17):e3278. PubMed abstract / Full Text

McCorquodale D, Pucillo EM, Johnson NE.
Management of Charcot-Marie-Tooth disease: improving long-term care with a multidisciplinary approach.
J Multidiscip Healthc. 2016;9:7-19. PubMed abstract / Full Text

Miller LJ, Saporta AS, Sottile SL, Siskind CE, Feely SM, Shy ME.
Strategy for genetic testing in Charcot-Marie-disease.
Acta Myol. 2011;30(2):109-16. PubMed abstract / Full Text

Murphy SM, Laura M, Fawcett K, Pandraud A, Liu YT, Davidson GL, Rossor AM, Polke JM, Castleman V, Manji H, Lunn MP, Bull K, Ramdharry G, Davis M, Blake JC, Houlden H, Reilly MM.
Charcot-Marie-Tooth disease: frequency of genetic subtypes and guidelines for genetic testing.
J Neurol Neurosurg Psychiatry. 2012;83(7):706-10. PubMed abstract / Full Text

Theadom A, Roxburgh R, MacAulay E, O'Grady G, Burns J, Parmar P, Jones K, Rodrigues M.
Prevalence of Charcot-Marie-Tooth disease across the lifespan: a population-based epidemiological study.
BMJ Open. 2019;9(6):e029240. PubMed abstract / Full Text

Wang Y, Yin F.
A Review of X-linked Charcot-Marie-Tooth Disease.
J Child Neurol. 2016;31(6):761-72. PubMed abstract

van Paassen BW, van der Kooi AJ, van Spaendonck-Zwarts KY, Verhamme C, Baas F, de Visser M.
PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies.
Orphanet J Rare Dis. 2014;9:38. PubMed abstract / Full Text