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Genetics Home Reference: your guide to understanding genetic conditions
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Andermann syndrome

Reviewed June 2008

What is Andermann syndrome?

Andermann syndrome is a disorder that damages the nerves used for muscle movement and sensation (motor and sensory neuropathy). Absence (agenesis) or malformation of the tissue connecting the left and right halves of the brain (corpus callosum) also occurs in most people with this disorder.

People affected by Andermann syndrome have abnormal or absent reflexes (areflexia) and weak muscle tone (hypotonia). They experience muscle wasting (amyotrophy), severe progressive weakness and loss of sensation in the limbs, and rhythmic shaking (tremors). They typically begin walking between ages 3 and 4 and lose this ability by their teenage years. As they get older, people with this disorder frequently develop joint deformities called contractures, which restrict the movement of certain joints. Most affected individuals also develop abnormal curvature of the spine (scoliosis), which may require surgery.

Andermann syndrome also results in abnormal function of certain cranial nerves, which emerge directly from the brain and extend to various areas of the head and neck. Cranial nerve problems may result in facial muscle weakness, drooping eyelids (ptosis), and difficulty following movements with the eyes (gaze palsy).

Individuals with Andermann syndrome usually have intellectual disability, which may be mild to severe, and some experience seizures. They may also develop psychiatric symptoms such as depression, anxiety, agitation, paranoia, and hallucinations, which usually appear in adolescence.

Some people with Andermann syndrome have atypical physical features such as widely spaced eyes (ocular hypertelorism); a wide, short skull (brachycephaly); a high arch of the hard palate at the roof of the mouth; a big toe that crosses over the other toes; and partial fusion (syndactyly) of the second and third toes.

Andermann syndrome is associated with a shortened life expectancy, but affected individuals typically live into adulthood.

How common is Andermann syndrome?

Andermann syndrome is most often seen in the French-Canadian population of the Saguenay-Lac-St.-Jean and Charlevoix regions of northeastern Quebec. In this population, Andermann syndrome occurs in almost 1 in 2,000 newborns. Only a few individuals with this disorder have been identified in other regions of the world.

What genes are related to Andermann syndrome?

Mutations in the SLC12A6 gene cause Andermann syndrome. The SLC12A6 gene provides instructions for making a protein called a K-Cl cotransporter. This protein is involved in moving charged atoms (ions) of potassium (K) and chlorine (Cl) across the cell membrane. The positively charged potassium ions and negatively charged chlorine ions are moved together (cotransported), so that the charges inside and outside the cell membrane are unchanged (electroneutral).

Electroneutral cotransport of ions across cell membranes is involved in many functions of the body. While the specific function of the K-Cl cotransporter produced from the SLC12A6 gene is unknown, it seems to be critical for the development and maintenance of nerve tissue. It may be involved in regulating the amounts of potassium, chlorine, or water in cells and intercellular spaces. The K-Cl cotransporter protein may also help regulate the activity of other proteins that are sensitive to ion concentrations.

Mutations in the SLC12A6 gene that cause Andermann syndrome disrupt the function of the K-Cl cotransporter protein. The lack of functional protein normally produced from the SLC12A6 gene is believed to interfere with the development of the corpus callosum and maintenance of the nerves that transmit signals needed for movement and sensation, resulting in the signs and symptoms of Andermann syndrome.

Related Gene(s)

Changes in this gene are associated with Andermann syndrome.

  • SLC12A6

How do people inherit Andermann syndrome?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of Andermann syndrome?

These resources address the diagnosis or management of Andermann syndrome and may include treatment providers.

  • Gene Review: Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum (http://www.ncbi.nlm.nih.gov/books/NBK1372)
  • Genetic Testing Registry: Andermann syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0795950)

You might also find information on the diagnosis or management of Andermann syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/andermann-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/andermann-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Andermann syndrome?

You may find the following resources about Andermann syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Andermann syndrome?

  • ACCPN
  • agenesis of corpus callosum with neuronopathy
  • agenesis of corpus callosum with peripheral neuropathy
  • agenesis of corpus callosum with polyneuropathy
  • Charlevoix disease
  • hereditary motor and sensory neuropathy with agenesis of the corpus callosum
  • HMSN/ACC

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Andermann syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Andermann syndrome?

agenesis ; anxiety ; atypical ; autosomal ; autosomal recessive ; big toe ; brachycephaly ; cell ; cell membrane ; corpus callosum ; cranial nerves ; depression ; disability ; gene ; hallucinations ; hereditary ; hypertelorism ; hypotonia ; inherited ; ions ; joint ; malformation ; motor ; muscle tone ; neuropathy ; ocular hypertelorism ; palate ; palsy ; peripheral ; peripheral neuropathy ; population ; potassium ; protein ; ptosis ; recessive ; scoliosis ; sensory neuropathy ; surgery ; syndactyly ; syndrome ; teenage ; tissue ; wasting

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • OMIM: AGENESIS OF THE CORPUS CALLOSUM WITH PERIPHERAL NEUROPATHY (http://omim.org/entry/218000)
  • Dupré N, Bouchard JP, Brais B, Rouleau GA. Hereditary ataxia, spastic paraparesis and neuropathy in the French-Canadian population. Can J Neurol Sci. 2006 May;33(2):149-57. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16736723?dopt=Abstract)
  • Dupré N, Howard HC, Mathieu J, Karpati G, Vanasse M, Bouchard JP, Carpenter S, Rouleau GA. Hereditary motor and sensory neuropathy with agenesis of the corpus callosum. Ann Neurol. 2003 Jul;54(1):9-18. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12838516?dopt=Abstract)
  • Gene Review: Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum (http://www.ncbi.nlm.nih.gov/books/NBK1372)
  • Howard HC, Mount DB, Rochefort D, Byun N, Dupré N, Lu J, Fan X, Song L, Rivière JB, Prévost C, Horst J, Simonati A, Lemcke B, Welch R, England R, Zhan FQ, Mercado A, Siesser WB, George AL Jr, McDonald MP, Bouchard JP, Mathieu J, Delpire E, Rouleau GA. The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosum. Nat Genet. 2002 Nov;32(3):384-92. Epub 2002 Oct 7. Erratum in: Nat Genet 2002 Dec;32(4):681. (http://www.ncbi.nlm.nih.gov/pubmed/12368912?dopt=Abstract)
  • Salin-Cantegrel A, Rivière JB, Dupré N, Charron FM, Shekarabi M, Karéméra L, Gaspar C, Horst J, Tekin M, Deda G, Krause A, Lippert MM, Willemsen MA, Jarrar R, Lapointe JY, Rouleau GA. Distal truncation of KCC3 in non-French Canadian HMSN/ACC families. Neurology. 2007 Sep 25;69(13):1350-5. (http://www.ncbi.nlm.nih.gov/pubmed/17893295?dopt=Abstract)
  • Uyanik G, Elcioglu N, Penzien J, Gross C, Yilmaz Y, Olmez A, Demir E, Wahl D, Scheglmann K, Winner B, Bogdahn U, Topaloglu H, Hehr U, Winkler J. Novel truncating and missense mutations of the KCC3 gene associated with Andermann syndrome. Neurology. 2006 Apr 11;66(7):1044-8. Erratum in: Neurology. 2006 Oct 24;67(8):1528. (http://www.ncbi.nlm.nih.gov/pubmed/16606917?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: June 2008
Published: September 15, 2014