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Hereditary spastic paraplegia 63(SPG63)

MedGen UID:
816625
Concept ID:
C3810295
Disease or Syndrome
Synonym: Spastic paraplegia 63, autosomal recessive
SNOMED CT: Autosomal recessive spastic paraplegia type 63 (726610000)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): AMPD2 (1p13.3)
 
Monarch Initiative: MONDO:0014305
OMIM®: 615686
Orphanet: ORPHA401805

Definition

An extremely rare and complex form of hereditary spastic paraplegia with characteristics of onset in infancy of spastic paraplegia (presenting with delayed walking and a scissors gait) associated with short stature and normal cognition. Periventricular deep white matter changes in the corpus callosum are noted on brain imaging. SPG63 is caused by a homozygous mutation in the AMPD2 gene (1p13.3) encoding AMP deaminase 2. [from SNOMEDCT_US]

Clinical features

From HPO
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Clonus
MedGen UID:
40341
Concept ID:
C0009024
Sign or Symptom
A series of rhythmic and involuntary muscle contractions (at a frequency of about 5 to 7 Hz) that occur in response to an abruptly applied and sustained stretch.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
Spastic paraplegia
MedGen UID:
20882
Concept ID:
C0037772
Disease or Syndrome
Spasticity and weakness of the leg and hip muscles.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Scissor gait
MedGen UID:
68547
Concept ID:
C0231698
Finding
A type of spastic paraparetic gait in which the muscle tone in the adductors is marked. It is characterized by hypertonia and flexion in the legs, hips and pelvis accompanied by extreme adduction leading to the knees and thighs hitting, or sometimes even crossing, in a scissors-like movement. The opposing muscles (abductors) become comparatively weak from lack of use.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk. In general, this can refer to neurological diseases but also fractures or other sources of pain that is triggered upon walking. However, in the current context gait disturbance refers to difficulty walking on the basis of a neurological or muscular disease.
Impaired vibration sensation at ankles
MedGen UID:
343107
Concept ID:
C1854372
Finding
A decrease in the ability to perceive vibration at the ankles. Clinically, this is usually tested with a tuning fork which vibrates at 128 Hz and is applied to the malleoli of the ankles.
Abnormal periventricular white matter morphology
MedGen UID:
435926
Concept ID:
C2673431
Finding
A structural abnormality of the myelinated axons (white matter) located near the cerebral ventricles.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary spastic paraplegia 63
Follow this link to review classifications for Hereditary spastic paraplegia 63 in Orphanet.

Professional guidelines

PubMed

Aleksovska K, Kobulashvili T, Costa J, Zimmermann G, Ritchie K, Reinhard C, Vignatelli L, Fanciulli A, Damian M, Pavlakova L, Burgunder JM, Kopishinskaya S, Rakusa M, Kovacs N, Erdogan FF, Linton LR, Copetti M, Lamperti C, Servidei S, Evangelista T, Ayme S, Pareyson D, Sellner J, Krarup C, de Visser M, van den Bergh P, Toscano A, Graessner H, Berger T, Bassetti C, Vidailhet M, Trinka E, Deuschl G, Federico A, Leone MA
Eur J Neurol 2022 Jun;29(6):1571-1586. Epub 2022 Mar 23 doi: 10.1111/ene.15267. PMID: 35318776

Recent clinical studies

Etiology

Xing F, Du J
Neurol Sci 2022 Aug;43(8):4989-4996. Epub 2022 Mar 28 doi: 10.1007/s10072-022-05921-3. PMID: 35348942
Lai LL, Chen YJ, Li YL, Lin XH, Wang MW, Dong EL, Wang N, Chen WJ, Lin X
Ann Clin Transl Neurol 2020 Oct;7(10):1862-1869. Epub 2020 Aug 29 doi: 10.1002/acn3.51169. PMID: 32860341Free PMC Article
De la Casa-Fages B, Fernández-Eulate G, Gamez J, Barahona-Hernando R, Morís G, García-Barcina M, Infante J, Zulaica M, Fernández-Pelayo U, Muñoz-Oreja M, Urtasun M, Olaskoaga A, Zelaya V, Jericó I, Saez-Villaverde R, Catalina I, Sola E, Martínez-Sáez E, Pujol A, Ruiz M, Schlüter A, Spinazzola A, Muñoz-Blanco JL, Grandas F, Holt I, Álvarez V, López de Munaín A
Mov Disord 2019 Oct;34(10):1547-1561. Epub 2019 Aug 21 doi: 10.1002/mds.27812. PMID: 31433872
Cui F, Sun L, Qiao J, Xiong J, Zhao Y, Li J, Li M, Chen S, Huang X
Neurol Res 2018 Dec;40(12):1088-1093. doi: 10.1080/01616412.2018.1522412. PMID: 30352018
Erichsen AK, Koht J, Stray-Pedersen A, Abdelnoor M, Tallaksen CM
Brain 2009 Jun;132(Pt 6):1577-88. Epub 2009 Mar 31 doi: 10.1093/brain/awp056. PMID: 19339254

Diagnosis

Xing F, Du J
Neurol Sci 2022 Aug;43(8):4989-4996. Epub 2022 Mar 28 doi: 10.1007/s10072-022-05921-3. PMID: 35348942
Du J
J Clin Neurosci 2021 Mar;85:67-71. Epub 2021 Jan 15 doi: 10.1016/j.jocn.2020.11.036. PMID: 33581793
Kraatari M, Tuominen H, Tuupanen S, Haapaniemi T, Moilanen J, Rahikkala E
Eur J Med Genet 2020 Nov;63(11):104040. Epub 2020 Aug 14 doi: 10.1016/j.ejmg.2020.104040. PMID: 32805447
Cui F, Sun L, Qiao J, Xiong J, Zhao Y, Li J, Li M, Chen S, Huang X
Neurol Res 2018 Dec;40(12):1088-1093. doi: 10.1080/01616412.2018.1522412. PMID: 30352018
Erichsen AK, Koht J, Stray-Pedersen A, Abdelnoor M, Tallaksen CM
Brain 2009 Jun;132(Pt 6):1577-88. Epub 2009 Mar 31 doi: 10.1093/brain/awp056. PMID: 19339254

Therapy

Kimoto Y, Oshino S, Tani N, Hosomi K, Khoo HM, Fujita Y, Miura S, Iwata T, Emura T, Matsuhashi T, Onoda Y, Ishiuchi T, Yanagisawa T, Hirata M, Kishima H
Neurol Med Chir (Tokyo) 2023 Dec 15;63(12):535-541. Epub 2023 Sep 23 doi: 10.2176/jns-nmc.2022-0359. PMID: 37743509Free PMC Article
Chen X, Dong T, Hu Y, De Pace R, Mattera R, Eberhardt K, Ziegler M, Pirovolakis T, Sahin M, Bonifacino JS, Ebrahimi-Fakhari D, Gray SJ
J Clin Invest 2023 May 15;133(10) doi: 10.1172/JCI164575. PMID: 36951961Free PMC Article
Hamanaka K, Miyatake S, Zerem A, Lev D, Blumkin L, Yokochi K, Fujita A, Imagawa E, Iwama K, Nakashima M, Mitsuhashi S, Mizuguchi T, Takata A, Miyake N, Saitsu H, van der Knaap MS, Lerman-Sagie T, Matsumoto N
J Hum Genet 2018 Dec;63(12):1223-1229. Epub 2018 Sep 27 doi: 10.1038/s10038-018-0516-x. PMID: 30258207
Koh K, Ishiura H, Beppu M, Shimazaki H, Ichinose Y, Mitsui J, Kuwabara S, Tsuji S, Takiyama Y; Japan Spastic Paraplegia Research Consortium
J Hum Genet 2018 Sep;63(9):1009-1013. Epub 2018 Jun 18 doi: 10.1038/s10038-018-0477-0. PMID: 29915212
Franco-Hernández JA, Muñoz Rodríguez L, Ortiz de Landázuri PJ, García Hernández A
Braz J Anesthesiol 2013 Jan;63(1):113-5. Epub 2013 Aug 7 doi: 10.1016/j.bjane.2012.05.002. PMID: 24565095

Prognosis

Kimoto Y, Oshino S, Tani N, Hosomi K, Khoo HM, Fujita Y, Miura S, Iwata T, Emura T, Matsuhashi T, Onoda Y, Ishiuchi T, Yanagisawa T, Hirata M, Kishima H
Neurol Med Chir (Tokyo) 2023 Dec 15;63(12):535-541. Epub 2023 Sep 23 doi: 10.2176/jns-nmc.2022-0359. PMID: 37743509Free PMC Article
Xing F, Du J
Neurol Sci 2022 Aug;43(8):4989-4996. Epub 2022 Mar 28 doi: 10.1007/s10072-022-05921-3. PMID: 35348942
Hamanaka K, Miyatake S, Zerem A, Lev D, Blumkin L, Yokochi K, Fujita A, Imagawa E, Iwama K, Nakashima M, Mitsuhashi S, Mizuguchi T, Takata A, Miyake N, Saitsu H, van der Knaap MS, Lerman-Sagie T, Matsumoto N
J Hum Genet 2018 Dec;63(12):1223-1229. Epub 2018 Sep 27 doi: 10.1038/s10038-018-0516-x. PMID: 30258207
Jia X, Madireddy L, Caillier S, Santaniello A, Esposito F, Comi G, Stuve O, Zhou Y, Taylor B, Kilpatrick T, Martinelli-Boneschi F, Cree BAC, Oksenberg JR, Hauser SL, Baranzini SE
Ann Neurol 2018 Jul;84(1):51-63. Epub 2018 Jul 3 doi: 10.1002/ana.25263. PMID: 29908077Free PMC Article
Webb S, Patterson V, Hutchinson M
J Neurol Neurosurg Psychiatry 1997 Nov;63(5):628-32. doi: 10.1136/jnnp.63.5.628. PMID: 9408105Free PMC Article

Clinical prediction guides

Chen X, Dong T, Hu Y, De Pace R, Mattera R, Eberhardt K, Ziegler M, Pirovolakis T, Sahin M, Bonifacino JS, Ebrahimi-Fakhari D, Gray SJ
J Clin Invest 2023 May 15;133(10) doi: 10.1172/JCI164575. PMID: 36951961Free PMC Article
Xing F, Du J
Neurol Sci 2022 Aug;43(8):4989-4996. Epub 2022 Mar 28 doi: 10.1007/s10072-022-05921-3. PMID: 35348942
Du J
J Clin Neurosci 2021 Mar;85:67-71. Epub 2021 Jan 15 doi: 10.1016/j.jocn.2020.11.036. PMID: 33581793
De la Casa-Fages B, Fernández-Eulate G, Gamez J, Barahona-Hernando R, Morís G, García-Barcina M, Infante J, Zulaica M, Fernández-Pelayo U, Muñoz-Oreja M, Urtasun M, Olaskoaga A, Zelaya V, Jericó I, Saez-Villaverde R, Catalina I, Sola E, Martínez-Sáez E, Pujol A, Ruiz M, Schlüter A, Spinazzola A, Muñoz-Blanco JL, Grandas F, Holt I, Álvarez V, López de Munaín A
Mov Disord 2019 Oct;34(10):1547-1561. Epub 2019 Aug 21 doi: 10.1002/mds.27812. PMID: 31433872
Cui F, Sun L, Qiao J, Xiong J, Zhao Y, Li J, Li M, Chen S, Huang X
Neurol Res 2018 Dec;40(12):1088-1093. doi: 10.1080/01616412.2018.1522412. PMID: 30352018

Recent systematic reviews

Du J
J Clin Neurosci 2021 Mar;85:67-71. Epub 2021 Jan 15 doi: 10.1016/j.jocn.2020.11.036. PMID: 33581793

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