Andermann syndrome

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Andermann syndrome
Other namesKCC3 axonopathy, agenesis of corpus callosum with neuronopathy, Charlevoix disease
This condition is inherited in an autosomal recessive manner.
SpecialtyMedical genetics, neurology Edit this on Wikidata

Andermann syndrome, also known as agenesis of corpus callosum with neuronopathy (ACCPN), Charlevoix disease and KCC3 axonopathy among other names,[1] 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 callosum.[1][2][3][4][5]

It was first described in 1972 by Frederick and Eva Andermann et al.[3][6][7]

Symptoms and signs

Symptoms and signs involve both the central and peripheral nervous systems starting in infancy:[2][4]

Genetics

The inheritance pattern is autosomal recessive[4] and involves nonsense[8] and missense[9] mutations of the SLC12A6 gene which codes for an axonal cell membrane protein of the same name, that functions as a co-transporter of potassium ions and chloride ions. The normal presence of these channels[10] in axons of both the central nervous system[11] and peripheral nervous system accounts for the symptoms and signs arising from brain[12] and nerves.[13]

The disease has been modelled in transgenic mice.[14] Dogs show a different phenotype from humans, with predominantly spinocerebellar ataxia.[15]

Neuropathology

Autopsy examination of eight cases has shown both developmental and degenerative neuropathologic features in this disease, consistent with clinical duality as both a neurodevelopmental and neurodegenerative disorder.[16]

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 anteroposterior 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 attempting regrowth.[17] Damaged axons can also show a sign of inhibition of axonal transport, forming axonal spheroids. These spheroids can occur throughout the cerebral hemispheres, explaining the psychotic symptoms by disconnection of the brain from itself by axonal functional disruption.[16]

In the peripheral nervous system (PNS), the disease is more severe. While most nervous system diseases affect either central nervous system (CNS) or PNS, this disease affects both, but the changes in the PNS 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.[16] The lack of innervation of the body musculature during development gives rise to small body weights, often below 40 kg (88 lb), remarkable in view of the preserved brain weights.[16]

Diagnosis

A typical diagnostic workup includes:[18]

  • Clinical features
  • Electrophysiologic testing
  • Molecular genetic testing (SLC12A6)
  • Magnetic resonance imaging of the brain (revealing in 60% of the patients callosal agenesis and in 10% partial callosal agenesis)

Treatment

Currently, no cure is known, but some symptoms may be treated, such as neuroleptics for the psychiatric problems.[5]

Prognosis

The prognosis is poor. Patients are usually wheelchair bound by their 20s and die by their 30s.[4][5]

Prevalence

The prevalence rate has been estimated to be less than one per 1,000,000 worldwide,[4] and 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 one in 2100 in live births, and a carrier rate of one in 23.[5] This genetic disease, along with the SLC12A6 mutation, has also been described in Turkey,[19] Algeria,[20]Tanzania,[21] Bulgaria[22] and Norway.[23]

References

  1. ^ a b "Andermann syndrome". Genetics Home Reference. NIH. Retrieved 19 January 2017.
  2. ^ a b "Andermann syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2017-01-19.
  3. ^ a b "AGENESIS OF THE CORPUS CALLOSUM WITH PERIPHERAL NEUROPATHY; ACCPN". www.omim.org. Retrieved 2017-01-19.
  4. ^ a b c d e RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Corpus callosum agenesis neuronopathy syndrome". www.orpha.net. Retrieved 2017-01-19.{{cite web}}: CS1 maint: numeric names: authors list (link)
  5. ^ a b c d Dupré, Nicolas; Howard, Heidi C.; Rouleau, Guy A. (1993-01-01). "Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum". In Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora J.H.; Bird, Thomas D.; Ledbetter, Nikki; Mefford, Heather C. (eds.). GeneReviews. Seattle (WA): University of Washington, Seattle. PMID 20301546.
  6. ^ Andermann, E; Andermann, F; Joubert, M (1972). "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. 97: 242-244.
  7. ^ Andermann, E; Andermann, F; Joubert, D; Melançon, D; Karpati, G; Carpenter, S (1975). "Three familial midline malformation syndromes of the central nervous system: agenesis of the corpus callosum and anterior horn-cell disease; agenesis of cerebellar vermis; and atrophy of the cerebellar vermis". Birth Defects Original Article Series. 11 (2): 269–293. PMID 1227532.
  8. ^ 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, J-P; Mathieu, J; Delpire, E; Rouleau, GA (2002). "The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosum". Nature Genetics. 32 (3): 384–392. doi:10.1038/ng1002. PMID 12368912.
  9. ^ Uyanik, G.; Elcioglu, N.; Penzien, J.; Gross, C.; Yilmaz, Y.; Olmez, A.; Demir, E.; Wahl, D.; Scheglmann, K. (2006). "Novel truncating and missense mutations of the KCC3 gene associated with Andermann syndrome". Neurology. 66 (7): 1044–1048. doi:10.1212/01.wnl.0000204181.31175.8b. ISSN 1526-632X. PMID 16606917. S2CID 280621.
  10. ^ Garneau, AP; Marcoux, AA; Frenette-Cotton, R; Mac-Way, F; Lavoie, JL; Isenring, P (2017). "Molecular insights into the normal operation, regulation, and multisystemic roles of K+-Cl- cotransporter 3 (KCC3)". American Journal of Physiology. Cell Physiology. 313 (5): C516–C532. doi:10.1152/ajpcell.00106.2017. PMID 28814402.
  11. ^ Shekarabi, M; Salin-Cantegrel, A; Laganière, J; Gaudet, R; Dion, P; Rouleau, GA (2011). "Cellular expression of the K+-Cl- cotransporter KCC3 in the central nervous system of mouse". Brain Research. 1374: 15–26. doi:10.1016/j.brainres.2010.12.010. PMID 21147077.
  12. ^ Filteau, MJ; Pourcher, E; Bouchard, RH; Baruch, P; Mathieu, J; Bédard, F; Simard, N; Vincent, P (1991). "Corpus callosum agenesis and psychosis in Andermann syndrome". Archives of Neurology. 48 (12): 1275–1280. doi:10.1001/archneur.1991.00530240079027. PMID 1668979.
  13. ^ Larbrisseau, A; Vanasse, M; Brochu, P; Jasmin, G (1984). "The Andermann syndrome: agenesis of the corpus callosum associated with mental retardation and progressive sensorimotor neuronopathy". Canadian Journal of Neurological Sciences. 11 (2): 257–261. doi:10.1017/s0317167100045509. PMID 6329500.
  14. ^ Shekarabi, M; Moldrich, RX; Rasheed, S; Salin-Cantegrel, A; Laganière, J; Rochefort, D; Hince, P; Huot, K; Gaudet, R; Kurniawan, N; Sotocinal, SG; Ritchie, J; Dion, PA; Mogil, JS; Richards, LJ; Rouleau, GA (2012). "Loss of neuronal potassium/chloride cotransporter 3 (KCC3) is responsible for the degenerative phenotype in a conditional mouse model of hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum". Journal of Neuroscience. 32 (11): 3865–3876. doi:10.1523/JNEUROSCI.3679-11.2012. PMC 6703451. PMID 22423107.
  15. ^ Van Poucke, M; Stee, K; Sonck, L; Stock, E; Bosseler, S; Van Dorpe, J; Van Nieuwerburgh, F; Deforce, D; Peelman, LJ; Van Ham, L; Bhatti, SFM; Broeckx, BJG (2019). "Truncating SLC12A6 variants cause different clinical phenotypes in humans and dogs". European Journal of Human Genetics. 27 (10): 1561–1568. doi:10.1038/s41431-019-0432-3. PMC 6777613. PMID 31160700.
  16. ^ a b c d Auer RN, Laganière JL, Robitaille YO, Richardson J, Dion PA, Rouleau GA, Shekarabi M (2016). "KCC3 axonopathy: neuropathological features in the central and peripheral nervous system". Modern Pathology. 29 (9): 962–976. doi:10.1038/modpathol.2016.90. PMID 27230413.
  17. ^ Sung, JH (1987). "Tangled masses of central axons (central axonomas) in the brain stem: anatomical evidence for the regenerative growth of human central axons". Journal of Neuropathology and Experimental Neurology. 46 (2): 200–213. doi:10.1097/00005072-198703000-00007. PMID 3819774.
  18. ^ Dupré, Nicolas (12 June 2014). "Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum". University of Washington, Seattle. Retrieved 18 April 2020.
  19. ^ Demir, E; Irobi, J; Erdem, S; Demirci, M; Tan, E; Timmerman, V; De Jonghe, P; Topaloglu, H (2003). "Andermann syndrome in a Turkish patient". Journal of Child Neurology. 18 (1): 76–79. doi:10.1177/08830738030180011901. PMID 12661946.
  20. ^ Lesca, G; Cournu-Rebeix, I; Azoulay-Cayla, A; Lyon-Caen, Q; Barois, A; Dulac, O; Fontaine, B (2001). "Andermann syndrome in an Algerian family: suggestion of phenotype and genetic homogeneity". Revue Neurologique. 157 (10): 1279–1281. PMID 11885521.
  21. ^ Deleu, D; Bamanikar, SA; Muirhead, D; Louon, A (1997). "Familial progressive sensorimotor neuropathy with agenesis of the corpus callosum (Andermann syndrome): a clinical, neuroradiological and histopathological study". European Neurology. 37 (2): 104–109. doi:10.1159/000117419. PMID 9058066.
  22. ^ Pacheva, I; Todorov, T; Halil, Z; Yordanova, R; Todorova, A; Geneva, I; Galabova, F; Ivanov, I (2019). "First case of Roma ethnic origin with Andermann syndrome: A novel frameshift mutation in exon 20 of SLC12A6 gene". American Journal of Medical Genetics. Part A. 179 (6): 1020–1024. doi:10.1002/ajmg.a.61110. PMID 30868738.
  23. ^ Løseth, S; Høyer, H; Le, K-M; Delpire, E; Kinge, E; Lande, A; Hilmarsen, HT; Fagerheim, T; Nilssen, Ø; Braathen, GJ (2023). "Late-onset sensory-motor axonal neuropathy, a novel SLC12A6-related phenotype". Brain. 146 (3): 912–922. doi:10.1093/brain/awac488. hdl:10037/28541. PMC 9976957. PMID 36542484.

External links

Retrieved from "https://mdwiki.org/wiki/Andermann_syndrome"