Andermann syndrome

Andermann syndrome
File:File:Autosomal recessive - en.svg
Synonyms	KCC3 axonopathy, Agenesis of corpus callosum with neuronopathy (ACCPN), Charlevoix disease
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Symptoms
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Diagnosis
Differential diagnosis
Prevention
Treatment
Medication
Prognosis
Frequency
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Andermann syndrome, also known as agenesis of corpus callosum with neuronopathy (ACCPN) and Charlevoix disease, among other names,<ref name="ghr">

Andermann syndrome(link). Genetics Home Reference. NIH.

</ref> is a very rare neurodegenerative genetic disorder that damages the nerves used to control muscles and related to sensation and is often associated with agenesis of the corpus collosum.<ref name="ghr" /><ref name=":0">

Andermann syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program(link). rarediseases.info.nih.gov.

Accessed 2017-01-19.

</ref><ref name=":1">

AGENESIS OF THE CORPUS CALLOSUM WITH PERIPHERAL NEUROPATHY; ACCPN(link). www.omim.org.

Accessed 2017-01-19.

</ref><ref name=":2"> RESERVED, INSERM US14 -- ALL RIGHTS. Orphanet: Corpus callosum agenesis neuronopathy syndrome(link). www.orpha.net.

Accessed 2017-01-19.

</ref><ref name=":3">Nicolas,

 GeneReviews, 
  
 Seattle (WA):University of Washington, Seattle,</ref>

It was first described by Eva Andermann et al. in 1972.<ref name=":1" /><ref name=":4">Uyanik, G.,

 Novel truncating and missense mutations of the KCC3 gene associated with Andermann syndrome, 
 Neurology, 
 
 Vol. 66(Issue: 7),
 pp. 1044–1048,
 DOI: 10.1212/01.wnl.0000204181.31175.8b,
 PMID: 16606917,</ref><ref>Andermann, Eva, 
 Familial agenesis of the corpus callosum with anterior horn cell disease: a syndrome of mental retardation, areflexia, and paraplegia, 
 Transactions of the American Neurological Association, 
 1972,
 Vol. 97,
 pp. 242–244,</ref>

Symptoms

Symptoms begin in infancy and include:<ref name=":0" /><ref name=":2" />

• hypotonia
• areflexia
• amyotrophy
• variable degrees of dysgenesis of the corpus callosum
• mild to severe intellectual and developmental delay
• psychiatric problems including paranoid delusions, depression, hallucinations and autistic-like behavior

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">,

 KCC3 axonopathy: neuropathological features in the central and peripheral nervous system, 
 Modern Pathology, 
 2016,
 Vol. 29(Issue: 9),
 pp. 962–976,
 DOI: 10.1038/modpathol.2016.90,
 PMID: 27230413,</ref> has shown both developmental and degenerative neuropathologic features in this disease, consistent with clinical duality as both a neurodevelopmental and neurodegenerative disorder.

In the central nervous system, accompanying the hypotonia at birth is hypoplasia of the corticospinal tracts. Another developmental feature is seen in the corpus callosum, which varies from absent to hypoplastic. The anterior commissure is almost always absent, but occasionally hypoplastic. A 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 spheroids. These spheroids 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 CNS or 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 muscles, including the 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> Dupré, Nicolas. Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum(link). '.

12 June 2014.

Accessed 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

There is currently no cure, but some symptoms may be treated such as neuroleptics for the psychiatric problems.<ref name=":3" />

Prognosis

The prognosis is poor. Patients are usually wheelchair bound by their 20s and die by their 30s.<ref name=":2" /><ref name=":3" />

Prevalence

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-Canadian population of the Saguenay and 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" />

References

<references />

External links

• Andermann syndrome at OMIM
• Andermann syndrome at Orpha.net
• Andermann syndrome at GARD

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