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Disease Profile

Roussy Levy syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

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ICD-10

G60.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Roussy Levy hereditary areflexic dystasia; Roussy-Levy disease; Hereditary areflexic dystasia;

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Roussy Levy syndrome is a term used to describe a neuromuscular disorder that typically becomes apparent during early childhood. This syndrome is considered a form of Charcot-Marie-Tooth (CMT) disease. Individuals with this disorder have clinical symptoms similar to Charcot-Marie-Tooth (CMT) disease type 1, which is characterized by muscle weakness and atrophy, poor judgement of movement (sensory ataxia), absent reflexes (areflexia) of the lower legs and hands, and abnormally high arches of the feet (pes cavus or "clawfoot"). Additional features of rhythmic shaking (static tremor) in the hands and an unsteady gait (gait ataxia) are specific to Roussy Levy syndrome.[1][2][3][4] This disorder is caused by issues with nerve conduction and sensory dysfunction.[1] Roussy Levy syndrome may result from a duplication of the PMP22 gene (which is also associated with CMT1A) or a mutation in the myelin protein zero (MPZ) gene (mutations in this gene are also associated with CMT1B).[3] Roussy Levy syndrome is inherited in an autosomal dominant manner.[2][4] Treatment is based on the signs and symptoms present in each person.[5]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Areflexia
Absent tendon reflexes
0001284
Decreased motor nerve conduction velocity
0003431
Decreased number of peripheral myelinated nerve fibers
0003380
Distal amyotrophy
Distal muscle wasting
0003693
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait

[ more ]

0001288
Hypertrophic nerve changes
0003382
Hyporeflexia
Decreased reflex response
Decreased reflexes

[ more ]

0001265
Percent of people who have these symptoms is not available through HPO
Abnormality of the immune system
Immunological abnormality
0002715
Autosomal dominant inheritance
0000006
Distal muscle weakness
Weakness of outermost muscles
0002460
Distal sensory impairment
Decreased sensation in extremities
0002936
Gait ataxia
Inability to coordinate movements when walking
0002066
Hammertoe
Hammer toe
Hammertoes

[ more ]

0001765
Juvenile onset
Signs and symptoms begin before 15 years of age
0003621
Kyphoscoliosis
0002751
Motor delay
0001270
Onion bulb formation
0003383
Pes cavus
High-arched foot
0001761
Segmental peripheral demyelination/remyelination
0003481
Slow progression
Signs and symptoms worsen slowly with time
0003677
Upper limb postural tremor
0007351

Diagnosis

Genetic testing for Roussy Levy syndrome (RLS) is available. RLS is one of the many different types of Charcot-Marie-Tooth disease (CMT). The genetics of the CMT disorders is complex. Once the different forms of CMT were classifed largely based upon their signs and symptoms. Now we know that alterations in the same gene can cause more than one type of CMT, and that a single type of CMT can be caused by alterations in more than one gene. 

RLS is caused by alterations in the MPZ or the PMP22 genes.[6] Alterations in these genes can also cause other forms of CMT (Charcot-Marie-Tooth type 1 and 2, Dejerine–Sottas neuropathy, hereditary neuropathy with liability to pressure palsies, and congenital hypomyelinating neuropathy).[7] A variety of other gene alterations have been implicated in other types of CMT (for example, CMT1 can also be caused by MP22, LITAF, EGR2, and NEFL gene alterations).[8]

We strongly recommend that you speak with your healthcare provider to discuss questions regarding your past testing result, and to learn if additional genetic testing would be informative for you. You may wish to speak with your provider regarding a referral to a genetics professional. Genetic professionals are a source of information for individuals and families regarding CMT testing. More information about genetic consultations is available from Genetics Home Reference at https://ghr.nlm.nih.gov/handbook/consult. To find a genetics clinic, we recommend that you contact your primary healthcare provider for a referral.

The following online resources can help you find a genetics professional in your community:

To view a list of laboratories that offer genetic testing of MPZ Click Here; for laboratories offering testing for PMP22 Click Here.

Treatment

There is a lack of published information regarding the treatment for this condition specifically; however, as Roussy Levy syndrome is considered a form of Charcot-Marie-Tooth (CMT) disease resembling CMT type 1, the symptoms may be managed in a similar manner.[6] While there is no cure for CMT1, treatment is specific to the signs and symptoms present in each individual and may include:[9][10]

  • Special shoes, including those with good ankle support and ankle/foot orthoses (AFOs) to correct foot drop and aid walking
  • Orthopedic surgery to correct severe pes cavus (high arches)
  • Forearm crutches or canes for walking stability
  • Serial night casting to help increase ankle flexibility
  • Acetaminophen or nonsteroidal anti-inflammatory agents for musculoskeletal pain
  • Antidepressants or anti seizure medications such as carbamazepine or gabapentin for neuropathic pain
  • Beta blockers or primidone for tremors
  • Physical therapy and occupational therapy
  • Exercise within each individual's capability

Additionally, there are certain medications that are potentially toxic to people with CMT as they may worsen CMT symptoms.[10] The Charcot-Marie-Tooth Association (CMTA), an organization supporting CMT, maintains an updated list of medications that present varying risks for worsening CMT neuropathy. Click here to view their list.

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Learn more

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    Where to Start

    • Genetics Home Reference (GHR) contains information on Roussy Levy syndrome. This website is maintained by the National Library of Medicine.
    • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

      In-Depth Information

      • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
      • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
      • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
      • PubMed is a searchable database of medical literature and lists journal articles that discuss Roussy Levy syndrome. Click on the link to view a sample search on this topic.

        References

        1. Canale & Beaty. Hereditary Motor and Sensory Neuropathies. Campbell's Operative Orthopaedics, 11th edition. Mosby, An Imprint of Elsevier; 2007;
        2. Charcot-Marie-Tooth disease. Genetics Home Reference (GHR). December, 2015; https://ghr.nlm.nih.gov/condition/charcot-marie-tooth-disease.
        3. Roussy-Levy Hereditary Areflexic Dystasia. Online Mendelian Inheritance in Man (OMIM). 2012; https://www.ncbi.nlm.nih.gov/omim/180800.
        4. Roussy Levy Syndrome. National Organization for Rare Disorders (NORD). 2004; https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/785/viewAbstract.
        5. Kleigman. Chapter 612 Hereditary Motor-Sensory Neuropathies. Nelson Textbook of Pediatrics, 18th edition. Saunders, An Imprint of Elsevier; 2007;
        6. McKusick VA. Roussy-Levy hereditary areflexic dystasia. Online Mendelian Inheritance in Man. April 19, 2012; https://omim.org/entry/180800.
        7. Szigeti K, Lupski JR. Charcot-Marie-Tooth disease. European Journal of Human Genetics. 2009;17:703-710; https://www.nature.com/ejhg/journal/v17/n6/abs/ejhg200931a.html. Accessed 4/26/2013.
        8. MPZ. Genetics Home Reference. January 2010; https://ghr.nlm.nih.gov/gene/MPZ. Accessed 4/26/2013.
        9. Cruse RP. Hereditary primary motor sensory neuropathies, including Charcot-Marie-Tooth disease. UpToDate. April 13, 2016; https://www.uptodate.com/contents/hereditary-primary-motor-sensory-neuropathies-including-charcot-marie-tooth-disease.
        10. Bird TD. Charcot-Marie-Tooth Neuropathy Type 1. GeneReviews. March 26, 2015; https://www.ncbi.nlm.nih.gov/books/NBK1205/.

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