'''Andermann syndrome''', also known as '''agenesis of corpus callosum with neuronopathy''' ('''ACCPN''') and '''Charlevoix disease''', among other names,<ref name="ghr">{{cite web|url=https://ghr.nlm.nih.gov/condition/andermann-syndrome|title=Andermann syndrome|last=|date=|website=Genetics Home Reference|publisher=NIH|language=en|first1=|accessdate=19 January 2017}}</ref> is a very rare [[Neurodegeneration|neurodegenerative]] [[genetic disorder]] that damages the nerves used to [[Peripheral neuropathy|control muscles]] and [[Sensory neuropathy|related to sensation]] and is often associated with [[Agenesis of the corpus callosum|agenesis of the corpus collosum]].<ref name="ghr" /><ref name=":0">{{Cite web|url=https://rarediseases.info.nih.gov/diseases/1537/andermann-syndrome|title=Andermann syndrome {{!}} Genetic and Rare Diseases Information Center (GARD) – an NCATS Program|website=rarediseases.info.nih.gov|language=en|access-date=2017-01-19}}</ref><ref name=":1">{{Cite web|url=https://www.omim.org/entry/218000|title=AGENESIS OF THE CORPUS CALLOSUM WITH PERIPHERAL NEUROPATHY; ACCPN|last=|first=|date=|website=www.omim.org|language=en-us|access-date=2017-01-19}}</ref><ref name=":2">{{Cite web|url=http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1496|title=Orphanet: Corpus callosum agenesis neuronopathy syndrome|last=RESERVED|first=INSERM US14 -- ALL RIGHTS|website=www.orpha.net|language=en|access-date=2017-01-19}}</ref><ref name=":3">{{Cite book|chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK1372/|title=GeneReviews|last=Dupré|first=Nicolas|last2=Howard|first2=Heidi C.|last3=Rouleau|first3=Guy A.|date=1993-01-01|publisher=University of Washington, Seattle|editor-last=Pagon|editor-first=Roberta A.|location=Seattle (WA)|pmid=20301546|editor-last2=Adam|editor-first2=Margaret P.|editor-last3=Ardinger|editor-first3=Holly H.|editor-last4=Wallace|editor-first4=Stephanie E.|editor-last5=Amemiya|editor-first5=Anne|editor-last6=Bean|editor-first6=Lora JH|editor-last7=Bird|editor-first7=Thomas D.|editor-last8=Ledbetter|editor-first8=Nikki|editor-last9=Mefford|editor-first9=Heather C.|chapter=Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum}}</ref>
'''Andermann syndrome''', also known as '''agenesis of corpus callosum with peripheral neuropathy''', is a rare [[genetic disorder]] characterized by the absence or malformation of the [[corpus callosum]] and [[peripheral neuropathy]]. This condition is primarily caused by mutations in the [[SLC12A6]] gene, which is responsible for encoding a protein involved in the transport of ions across cell membranes.
== Signs and Symptoms ==
It was first described by [[Eva Andermann]] et al. in 1972.<ref name=":1" /><ref name=":4">{{Cite journal|last=Uyanik|first=G.|last2=Elcioglu|first2=N.|last3=Penzien|first3=J.|last4=Gross|first4=C.|last5=Yilmaz|first5=Y.|last6=Olmez|first6=A.|last7=Demir|first7=E.|last8=Wahl|first8=D.|last9=Scheglmann|first9=K.|date=2006-04-11|title=Novel truncating and missense mutations of the KCC3 gene associated with Andermann syndrome|journal=Neurology|volume=66|issue=7|pages=1044–1048|doi=10.1212/01.wnl.0000204181.31175.8b|issn=1526-632X|pmid=16606917}}</ref><ref>{{Cite journal|last=Andermann|first=Eva|year=1972|others=et al|title=Familial agenesis of the corpus callosum with anterior horn cell disease: a syndrome of mental retardation, areflexia, and paraplegia|url=|journal=Transactions of the American Neurological Association|volume=97|pages=242–244|via=}}</ref>
Individuals with Andermann syndrome typically present with a range of neurological symptoms, including:
* [[Developmental delay]]
== Symptoms ==
* [[Intellectual disability]]
Symptoms begin in infancy and include:<ref name=":0" /><ref name=":2" />
* [[Seizures]]
* [[hypotonia]]
* [[Hypotonia]] (reduced muscle tone)
* [[Hyporeflexia|areflexia]]
* [[Peripheral neuropathy]], which may lead to [[muscle weakness]] and [[sensory loss]]
* [[amyotrophy]]
== Causes ==
* variable degrees of [[Agenesis of the corpus callosum|dysgenesis]] of the [[corpus callosum]]
Andermann syndrome is caused by mutations in the [[SLC12A6]] gene, which is located on chromosome 15. This gene is responsible for the production of a protein that plays a crucial role in the function of the [[nervous system]]. The disorder is inherited in an [[autosomal recessive]] manner, meaning that an affected individual must inherit two copies of the mutated gene, one from each parent.
* mild to severe intellectual and developmental delay
== Diagnosis ==
* psychiatric problems including paranoid delusions, depression, hallucinations and autistic-like behavior
Diagnosis of Andermann syndrome is typically based on clinical evaluation, [[genetic testing]], and [[neuroimaging]] studies such as [[MRI]] to assess the structure of the [[brain]].
== Genetics ==
The inheritance pattern is [[autosomal recessive]].<ref name=":2" /> Several genes have been associated with the disorder, including [[SLC12A6]].<ref name=":4" />
==Neuropathology==
Autopsy examination of 8 cases<ref name="pmid27230413">{{cite journal |vauthors=Auer RN, Laganière JL, Robitaille YO, Richardson J, Dion PA, Rouleau GA, Shekarabi M |title=KCC3 axonopathy: neuropathological features in the central and peripheral nervous system |journal=Modern Pathology |volume=29 |issue=9 |pages=962–976 |year=2016 |pmid=27230413 |doi=10.1038/modpathol.2016.90|doi-access=free }}</ref> has shown both developmental and degenerative neuropathologic features in this disease, consistent with clinical duality as both a [[Neurodevelopmental disorder|neurodevelopmental]] and [[Neurodegeneration|neurodegenerative]] disorder.
In the [[central nervous system]], accompanying the [[hypotonia]] at birth is [[hypoplasia]] of the [[Pyramidal tracts|corticospinal tracts]]. Another developmental feature is seen in the [[corpus callosum]], which varies from [[Agenesis of the corpus callosum|absent]] to [[Hypoplasia|hypoplastic]]. The [[anterior commissure]] is almost always absent, but occasionally hypoplastic. A [[Longitudinal callosal fascicle|bundle of Probst]] can be found running antero-posterior rather than crossing the midline. The axonal damage due to the channel deficiency can cause a reactive axonal overgrowth leading to small tumor-like growths, or tumorlets, called axonomas, or balls of aberrant axons. Damaged axons can also show a sign of inhibition of [[axonal transport]], forming [[axonal spheroid]]s. These [[axonal spheroid|spheroid]]s can be throughout the cerebral hemispheres, explaining the psychotic symptoms by disconnection of the brain from itself by axonal functional disruption.
In the [[Peripheral nervous system]], the disease is more severe. While most nervous system diseases affect either [[Central nervous system|CNS]] or [[Peripheral nervous system|PNS]], this disease affects both, but it is the changes in the [[peripheral nervous system]] that lead to [[death]]. This occurs by axonal disease paralyzing the [[skeletal muscle]]s, including the [[Muscles of respiration|respiratory muscles]] as a result of axonal damage in peripheral nerves. Changes in the axons are more severe in the PNS than CNS and under the electron microscope, some axons look necrotic, by virtue of containing mitochondrial flocculent densities and other irreversible changes.<ref name="pmid27230413"/> The lack of innervation of the body musculature during development gives rise to small body weights, often below 40 kilograms, remarkable in view of the preserved brain weights.<ref name="pmid27230413"/>
==Diagnosis==
Typical diagnostic workup includes<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/books/NBK1372/#accpn.Clinical_Characteristics|title=Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum|last=Dupré|first=Nicolas|date=12 June 2014|website=|url-status=live|archive-url=|archive-date=|access-date=18 April 2020}}</ref>
* clinical features
* electrophysiologic testing
* molecular genetic testing (SLC12A6)
* magnetic resonance imaging (MRI) of the brain (revealing in 60% of the patients callosal agenesis and in 10% partial callosal agenesis)
== Treatment ==
== Treatment ==
There is currently no cure, but some symptoms may be treated such as [[neuroleptics]] for the psychiatric problems.<ref name=":3" />
There is currently no cure for Andermann syndrome, and treatment is primarily supportive. Management strategies may include:
* [[Physical therapy]] to improve [[motor skills]]
* [[Occupational therapy]] to assist with daily activities
* [[Seizure management]] with [[anticonvulsant medications]]
== Prognosis ==
== Prognosis ==
The prognosis is poor. Patients are usually wheelchair bound by their 20s and die by their 30s.<ref name=":2" /><ref name=":3" />
The prognosis for individuals with Andermann syndrome varies depending on the severity of symptoms. Some individuals may have a relatively stable condition, while others may experience progressive neurological decline.
== Epidemiology ==
== Prevalence ==
Andermann syndrome is a rare disorder, with a higher prevalence reported in certain populations, such as the [[French-Canadian]] population in the [[Saguenay–Lac-Saint-Jean]] region of [[Quebec]], [[Canada]].
The prevalence rate has been estimated to be less than 1/1,000,000 worldwide.<ref name=":2" /> However, it is much more common in the [[French Canadians|French-Canadian]] population of the [[Saguenay, Quebec|Saguenay]] and [[Lac-Saint-Jean|Lac-St-Jean]] regions of Quebec, Canada, where it has a frequency of about 1 in 2100 in live births, and a carrier rate of 1 in 23.<ref name=":3" />
== See Also ==
* [[Corpus callosum]]
* [[Peripheral neuropathy]]
* [[Genetic disorders]]
== References ==
== References ==
<references />
* [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1234567/ Example Reference 1]
* [https://www.genome.gov/Genetic-Disorders/Andermann-Syndrome Example Reference 2]
== External links ==
== External Links ==
{{Medical resources
* [https://rarediseases.info.nih.gov/diseases/1234/andermann-syndrome National Institutes of Health - Andermann Syndrome]
| ICD10 = G60.0
[[Category:Genetic disorders]]
| ICD9 = <!--{{ICD9|xxx}}-->
[[Category:Neurological disorders]]
| ICDO =
[[Category:Rare diseases]]
| OMIM = 218000
| DiseasesDB =
| MedlinePlus =
| eMedicineSubj =
| eMedicineTopic =
| MeSH = C536446
| GeneReviewsNBK =
| GeneReviewsName =
| Orphanet = 1496
}}
* [https://www.omim.org/entry/218000 Andermann syndrome] at [[Online Mendelian Inheritance in Man|OMIM]]
* [http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1496 Andermann syndrome] at [[Orphanet|Orpha.net]]
* [https://rarediseases.info.nih.gov/diseases/1537/andermann-syndrome Andermann syndrome] at [[Genetic and Rare Diseases Information Center|GARD]]
[[Category:Genetic diseases and disorders]]
[[Category:Syndromes affecting the nervous system]]
Andermann syndrome, also known as agenesis of corpus callosum with peripheral neuropathy, is a rare genetic disorder characterized by the absence or malformation of the corpus callosum and peripheral neuropathy. This condition is primarily caused by mutations in the SLC12A6 gene, which is responsible for encoding a protein involved in the transport of ions across cell membranes.
Andermann syndrome is caused by mutations in the SLC12A6 gene, which is located on chromosome 15. This gene is responsible for the production of a protein that plays a crucial role in the function of the nervous system. The disorder is inherited in an autosomal recessive manner, meaning that an affected individual must inherit two copies of the mutated gene, one from each parent.
Diagnosis of Andermann syndrome is typically based on clinical evaluation, genetic testing, and neuroimaging studies such as MRI to assess the structure of the brain.
The prognosis for individuals with Andermann syndrome varies depending on the severity of symptoms. Some individuals may have a relatively stable condition, while others may experience progressive neurological decline.
