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Canavan Disease, Familial Form

MedGen UID:
148363
Concept ID:
C0751663
Disease or Syndrome
Synonym: Familial Form of Canavan Disease

Definition

The mild/juvenile form of Canavan disease is less common. Affected individuals have mildly delayed development of speech and motor skills starting in childhood. These delays may be so mild and nonspecific that they are never recognized as being caused by Canavan disease.

Neonatal/infantile Canavan disease is the most common and most severe form of the condition. Affected infants appear normal for the first few months of life, but by age 3 to 5 months, problems with development become noticeable. These infants usually do not develop motor skills such as turning over, controlling head movement, and sitting without support. Other common features of this condition include weak muscle tone (hypotonia), an unusually large head size (macrocephaly), and irritability. Feeding and swallowing difficulties, seizures, and sleep disturbances may also develop.

The life expectancy for people with Canavan disease varies. Most people with the neonatal/infantile form live only into childhood, although some survive into adolescence or beyond. People with the mild/juvenile form do not appear to have a shortened lifespan.

Canavan disease is a rare inherited disorder that damages the ability of nerve cells (neurons) in the brain to send and receive messages. This disease is one of a group of genetic disorders called leukodystrophies. Leukodystrophies disrupt the growth or maintenance of the myelin sheath, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. [from MedlinePlus Genetics]

Professional guidelines

PubMed

Bradbury AM, Ream MA
Semin Pediatr Neurol 2021 Apr;37:100876. Epub 2021 Feb 10 doi: 10.1016/j.spen.2021.100876. PMID: 33892849
Pleasure D, Guo F, Chechneva O, Bannerman P, McDonough J, Burns T, Wang Y, Hull V
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Matalon R, Matalon KM
Obstet Gynecol Clin North Am 2002 Jun;29(2):297-304. doi: 10.1016/s0889-8545(01)00003-1. PMID: 12108830

Recent clinical studies

Etiology

Thakkar RN, Patel D, Kioutchoukova IP, Al-Bahou R, Reddy P, Foster DT, Lucke-Wold B
Med Sci (Basel) 2024 Jan 25;12(1) doi: 10.3390/medsci12010007. PMID: 38390857Free PMC Article
Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR, Hart RG, Shestakovska O, Diaz R, Alings M, Lonn EM, Anand SS, Widimsky P, Hori M, Avezum A, Piegas LS, Branch KRH, Probstfield J, Bhatt DL, Zhu J, Liang Y, Maggioni AP, Lopez-Jaramillo P, O'Donnell M, Kakkar AK, Fox KAA, Parkhomenko AN, Ertl G, Störk S, Keltai M, Ryden L, Pogosova N, Dans AL, Lanas F, Commerford PJ, Torp-Pedersen C, Guzik TJ, Verhamme PB, Vinereanu D, Kim JH, Tonkin AM, Lewis BS, Felix C, Yusoff K, Steg PG, Metsarinne KP, Cook Bruns N, Misselwitz F, Chen E, Leong D, Yusuf S; COMPASS Investigators
N Engl J Med 2017 Oct 5;377(14):1319-1330. Epub 2017 Aug 27 doi: 10.1056/NEJMoa1709118. PMID: 28844192
Zayed H
Gene 2015 Apr 10;560(1):9-14. Epub 2015 Feb 7 doi: 10.1016/j.gene.2015.02.009. PMID: 25668701
Glicksman S, Borgen C, Blackstein M, Gordon A, Hanon I, Kusin D, Leibowitz B, Halle J
J Intellect Disabil Res 2013 Sep;57(9):815-25. Epub 2012 Jun 8 doi: 10.1111/j.1365-2788.2012.01576.x. PMID: 22676184
Perlman SJ, Mar S
Adv Exp Med Biol 2012;724:154-71. doi: 10.1007/978-1-4614-0653-2_13. PMID: 22411242

Diagnosis

Thakkar RN, Patel D, Kioutchoukova IP, Al-Bahou R, Reddy P, Foster DT, Lucke-Wold B
Med Sci (Basel) 2024 Jan 25;12(1) doi: 10.3390/medsci12010007. PMID: 38390857Free PMC Article
Zayed H
Gene 2015 Apr 10;560(1):9-14. Epub 2015 Feb 7 doi: 10.1016/j.gene.2015.02.009. PMID: 25668701
Canavan TN, Mathes EF, Frieden I, Shinkai K
J Am Acad Dermatol 2015 Feb;72(2):239-45. doi: 10.1016/j.jaad.2014.06.026. PMID: 25592340
Hoshino H, Kubota M
Pediatr Int 2014 Aug;56(4):477-83. doi: 10.1111/ped.12422. PMID: 24977939
Perlman SJ, Mar S
Adv Exp Med Biol 2012;724:154-71. doi: 10.1007/978-1-4614-0653-2_13. PMID: 22411242

Therapy

Canavan ME, Wang X, Ascha MS, Miksad RA, Showalter TN, Calip GS, Gross CP, Adelson KB
JAMA Oncol 2024 Jul 1;10(7):887-895. doi: 10.1001/jamaoncol.2024.1129. PMID: 38753341Free PMC Article
Mendell JR, Al-Zaidy SA, Rodino-Klapac LR, Goodspeed K, Gray SJ, Kay CN, Boye SL, Boye SE, George LA, Salabarria S, Corti M, Byrne BJ, Tremblay JP
Mol Ther 2021 Feb 3;29(2):464-488. Epub 2020 Dec 10 doi: 10.1016/j.ymthe.2020.12.007. PMID: 33309881Free PMC Article
Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR, Hart RG, Shestakovska O, Diaz R, Alings M, Lonn EM, Anand SS, Widimsky P, Hori M, Avezum A, Piegas LS, Branch KRH, Probstfield J, Bhatt DL, Zhu J, Liang Y, Maggioni AP, Lopez-Jaramillo P, O'Donnell M, Kakkar AK, Fox KAA, Parkhomenko AN, Ertl G, Störk S, Keltai M, Ryden L, Pogosova N, Dans AL, Lanas F, Commerford PJ, Torp-Pedersen C, Guzik TJ, Verhamme PB, Vinereanu D, Kim JH, Tonkin AM, Lewis BS, Felix C, Yusoff K, Steg PG, Metsarinne KP, Cook Bruns N, Misselwitz F, Chen E, Leong D, Yusuf S; COMPASS Investigators
N Engl J Med 2017 Oct 5;377(14):1319-1330. Epub 2017 Aug 27 doi: 10.1056/NEJMoa1709118. PMID: 28844192
Roscoe RB, Elliott C, Zarros A, Baillie GS
J Neurol Sci 2016 Jul 15;366:116-124. Epub 2016 May 10 doi: 10.1016/j.jns.2016.05.012. PMID: 27288788
Canavan TN, Mathes EF, Frieden I, Shinkai K
J Am Acad Dermatol 2015 Feb;72(2):239-45. doi: 10.1016/j.jaad.2014.06.026. PMID: 25592340

Prognosis

Canavan TN, Mathes EF, Frieden I, Shinkai K
J Am Acad Dermatol 2015 Feb;72(2):239-45. doi: 10.1016/j.jaad.2014.06.026. PMID: 25592340
Rodriguez D
Handb Clin Neurol 2013;113:1619-28. doi: 10.1016/B978-0-444-59565-2.00030-7. PMID: 23622383
Perlman SJ, Mar S
Adv Exp Med Biol 2012;724:154-71. doi: 10.1007/978-1-4614-0653-2_13. PMID: 22411242
Canavan TP, Doshi NR
Am Fam Physician 2000 Mar 1;61(5):1369-76. PMID: 10735343
Matalon R, Michals-Matalon K
Eur J Paediatr Neurol 1998;2(2):69-76. doi: 10.1016/s1090-3798(98)80044-5. PMID: 10724099

Clinical prediction guides

Canavan ME, Wang X, Ascha MS, Miksad RA, Showalter TN, Calip GS, Gross CP, Adelson KB
JAMA Oncol 2024 Jul 1;10(7):887-895. doi: 10.1001/jamaoncol.2024.1129. PMID: 38753341Free PMC Article
Danese S, Panaccione R, Abreu MT, Rubin DT, Ghosh S, Dignass A, Afzali A, Wolf DC, Chiorean MV, Vermeire S, Jain A, Charles L, Lawlor G, Osterman MT, Wu H, Canavan JB, Petersen A, Colombel JF, Regueiro M
J Crohns Colitis 2024 Feb 26;18(2):264-274. doi: 10.1093/ecco-jcc/jjad146. PMID: 37651686Free PMC Article
Striano P, Auvin S, Collins A, Horvath R, Scheffer IE, Tzadok M, Miller I, Kay Koenig M, Lacy A, Davis R, Garcia-Cazorla A, Saneto RP, Brandabur M, Blair S, Koutsoukos T, De Vivo D
Epilepsia 2022 Jul;63(7):1748-1760. Epub 2022 May 21 doi: 10.1111/epi.17263. PMID: 35441706Free PMC Article
Zhang J, Ban T, Zhou L, Ji H, Yan H, Shi Z, Cao B, Jiang Y, Wang J, Wu Y
J Neurol 2020 Sep;267(9):2612-2618. Epub 2020 May 9 doi: 10.1007/s00415-020-09889-y. PMID: 32388833
Baslow MH, Resnik TR
J Mol Neurosci 1997 Oct;9(2):109-25. doi: 10.1007/BF02736855. PMID: 9407392

Recent systematic reviews

Canavan TN, Mathes EF, Frieden I, Shinkai K
J Am Acad Dermatol 2015 Feb;72(2):239-45. doi: 10.1016/j.jaad.2014.06.026. PMID: 25592340
Smyth A, O'Donnell MJ, Yusuf S, Clase CM, Teo KK, Canavan M, Reddan DN, Mann JF
Am J Hypertens 2014 Oct;27(10):1277-84. Epub 2014 Feb 7 doi: 10.1093/ajh/hpt294. PMID: 24510182

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