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Hereditary spastic paraplegia 34(SPG34)

MedGen UID:
437069
Concept ID:
C2677897
Disease or Syndrome
Synonym: Spastic paraplegia 34, X-linked
SNOMED CT: X-linked spastic paraplegia type 34 (763370008)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Monarch Initiative: MONDO:0010418
OMIM®: 300750
Orphanet: ORPHA171607

Definition

A pure form of hereditary spastic paraplegia with late childhood to early adulthood-onset of slowly progressive spastic paraplegia with spastic gait and lower limb hyperreflexia, brisk tendon reflexes and ankle clonus. Lower limb pain and reduced lower limb vibratory sense is also reported in some older adult patients. [from SNOMEDCT_US]

Clinical features

From HPO
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.
Paraplegia
MedGen UID:
45323
Concept ID:
C0030486
Disease or Syndrome
Severe or complete weakness of both lower extremities with sparing of the upper extremities.
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.
Spastic gait
MedGen UID:
115907
Concept ID:
C0231687
Finding
Spasticity is manifested by increased stretch reflex which is intensified with movement velocity. This results in excessive and inappropriate muscle activation which can contribute to muscle hypertonia. Spastic gait is characterized by manifestations such as muscle hypertonia, stiff knee, and circumduction of the leg.
Impaired vibratory sensation
MedGen UID:
220959
Concept ID:
C1295585
Finding
A decrease in the ability to perceive vibration. Clinically, this is usually tested with a tuning fork which vibrates at 128 Hz and is applied to bony prominences such as the malleoli at the ankles or the metacarpal-phalangeal joints. There is a slow decay of vibration from the tuning fork. The degree of vibratory sense loss can be crudely estimated by counting the number of seconds that the examiner can perceive the vibration longer than the patient.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary spastic paraplegia 34
Follow this link to review classifications for Hereditary spastic paraplegia 34 in Orphanet.

Professional guidelines

PubMed

van de Pol LA, Burgert N, van Schie PEM, Slot KM, Gouw AA, Buizer AI
Childs Nerv Syst 2024 Mar;40(3):855-861. Epub 2023 Oct 3 doi: 10.1007/s00381-023-06159-w. PMID: 37783799Free PMC Article
Hedera P, Williamson JA, Rainier S, Alvarado D, Tukel T, Apak M, Fink JK
Prenat Diagn 2001 Mar;21(3):202-6. doi: 10.1002/1097-0223(200103)21:3<202::aid-pd4>3.0.co;2-u. PMID: 11260609

Recent clinical studies

Etiology

Fereshtehnejad SM, Saleh PA, Oliveira LM, Patel N, Bhowmick S, Saranza G, Kalia LV
Neurol Sci 2023 Mar;44(3):947-959. Epub 2022 Nov 28 doi: 10.1007/s10072-022-06516-8. PMID: 36441344Free PMC Article
MacWilliams BA, Carroll KL, Stotts AK, Kerr LM, Schwartz MH
Gait Posture 2022 Oct;98:34-38. Epub 2022 Aug 17 doi: 10.1016/j.gaitpost.2022.08.011. PMID: 36041285
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
Pearson TS, Pons R, Ghaoui R, Sue CM
Mov Disord 2019 May;34(5):625-636. Epub 2019 Mar 26 doi: 10.1002/mds.27655. PMID: 30913345
Reid E
J Med Genet 1997 Jun;34(6):499-503. doi: 10.1136/jmg.34.6.499. PMID: 9192272Free PMC Article

Diagnosis

Fereshtehnejad SM, Saleh PA, Oliveira LM, Patel N, Bhowmick S, Saranza G, Kalia LV
Neurol Sci 2023 Mar;44(3):947-959. Epub 2022 Nov 28 doi: 10.1007/s10072-022-06516-8. PMID: 36441344Free PMC Article
MacWilliams BA, Carroll KL, Stotts AK, Kerr LM, Schwartz MH
Gait Posture 2022 Oct;98:34-38. Epub 2022 Aug 17 doi: 10.1016/j.gaitpost.2022.08.011. PMID: 36041285
Pearson TS, Pons R, Ghaoui R, Sue CM
Mov Disord 2019 May;34(5):625-636. Epub 2019 Mar 26 doi: 10.1002/mds.27655. PMID: 30913345
Fink JK
Semin Neurol 2014 Jul;34(3):293-305. Epub 2014 Sep 5 doi: 10.1055/s-0034-1386767. PMID: 25192507
Reid E
J Med Genet 1997 Jun;34(6):499-503. doi: 10.1136/jmg.34.6.499. PMID: 9192272Free PMC Article

Therapy

van de Pol LA, Burgert N, van Schie PEM, Slot KM, Gouw AA, Buizer AI
Childs Nerv Syst 2024 Mar;40(3):855-861. Epub 2023 Oct 3 doi: 10.1007/s00381-023-06159-w. PMID: 37783799Free PMC Article
Schöls L, Rattay TW, Martus P, Meisner C, Baets J, Fischer I, Jägle C, Fraidakis MJ, Martinuzzi A, Saute JA, Scarlato M, Antenora A, Stendel C, Höflinger P, Lourenco CM, Abreu L, Smets K, Paucar M, Deconinck T, Bis DM, Wiethoff S, Bauer P, Arnoldi A, Marques W, Jardim LB, Hauser S, Criscuolo C, Filla A, Züchner S, Bassi MT, Klopstock T, De Jonghe P, Björkhem I, Schüle R
Brain 2017 Dec 1;140(12):3112-3127. doi: 10.1093/brain/awx273. PMID: 29126212Free PMC Article
Solowska JM, D'Rozario M, Jean DC, Davidson MW, Marenda DR, Baas PW
J Neurosci 2014 Jan 29;34(5):1856-67. doi: 10.1523/JNEUROSCI.3309-13.2014. PMID: 24478365Free PMC Article
Bonnefoy-Mazure A, Turcot K, Kaelin A, De Coulon G, Armand S
Res Dev Disabil 2013 Jan;34(1):495-504. Epub 2012 Oct 17 doi: 10.1016/j.ridd.2012.09.005. PMID: 23085499
Vanderver A, Tonduti D, Auerbach S, Schmidt JL, Parikh S, Gowans GC, Jackson KE, Brock PL, Patterson M, Nehrebecky M, Godfrey R, Zein WM, Gahl W, Toro C
Mol Genet Metab 2012 Sep;107(1-2):229-33. Epub 2012 Jun 1 doi: 10.1016/j.ymgme.2012.05.020. PMID: 22749184Free PMC Article

Prognosis

MacWilliams BA, Carroll KL, Stotts AK, Kerr LM, Schwartz MH
Gait Posture 2022 Oct;98:34-38. Epub 2022 Aug 17 doi: 10.1016/j.gaitpost.2022.08.011. PMID: 36041285
Vander Stichele G, Durr A, Yoon G, Schüle R, Blackstone C, Esposito G, Buffel C, Oliveira I, Freitag C, van Rooijen S, Hoffmann S, Thielemans L, Cowling BS
BMC Neurol 2022 Mar 24;22(1):115. doi: 10.1186/s12883-022-02595-4. PMID: 35331153Free PMC Article
Zhu Z, Zhang C, Zhao G, Liu Q, Zhong P, Zhang M, Tang W, Zhan F, Tian W, Wang Y, Yin K, Huang X, Jiang J, Liu X, Liu S, Zhou H, Luan X, Tang H, Wang Y, Chen S, Cao L
Parkinsonism Relat Disord 2019 Dec;69:125-133. Epub 2019 Nov 6 doi: 10.1016/j.parkreldis.2019.11.007. PMID: 31751864
Pearson TS, Pons R, Ghaoui R, Sue CM
Mov Disord 2019 May;34(5):625-636. Epub 2019 Mar 26 doi: 10.1002/mds.27655. PMID: 30913345
de Bot ST, Burggraaff RC, Herkert JC, Schelhaas HJ, Post B, Diekstra A, van Vliet RO, van der Knaap MS, Kamsteeg EJ, Scheffer H, van de Warrenburg BP, Verschuuren-Bemelmans CC, Kremer HP
Eur J Hum Genet 2013 Nov;21(11):1312-5. Epub 2013 Feb 27 doi: 10.1038/ejhg.2013.27. PMID: 23443022Free PMC Article

Clinical prediction guides

Santos Silva C, Correia Rodrigues C, Fortuna Baptista M, Oliveira Santos M, Gromicho M, Carvalho V, Correia Guedes L, de Carvalho M
Muscle Nerve 2024 Jul;70(1):152-156. Epub 2024 Apr 30 doi: 10.1002/mus.28100. PMID: 38687249
MacWilliams BA, Carroll KL, Stotts AK, Kerr LM, Schwartz MH
Gait Posture 2022 Oct;98:34-38. Epub 2022 Aug 17 doi: 10.1016/j.gaitpost.2022.08.011. PMID: 36041285
Liu X, Duan X, Zhang Y, Sun A, Fan D
Eur J Neurol 2020 Jul;27(7):1319-1326. Epub 2020 May 12 doi: 10.1111/ene.14260. PMID: 32298515
Zhu Z, Zhang C, Zhao G, Liu Q, Zhong P, Zhang M, Tang W, Zhan F, Tian W, Wang Y, Yin K, Huang X, Jiang J, Liu X, Liu S, Zhou H, Luan X, Tang H, Wang Y, Chen S, Cao L
Parkinsonism Relat Disord 2019 Dec;69:125-133. Epub 2019 Nov 6 doi: 10.1016/j.parkreldis.2019.11.007. PMID: 31751864
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

Recent systematic reviews

Fereshtehnejad SM, Saleh PA, Oliveira LM, Patel N, Bhowmick S, Saranza G, Kalia LV
Neurol Sci 2023 Mar;44(3):947-959. Epub 2022 Nov 28 doi: 10.1007/s10072-022-06516-8. PMID: 36441344Free PMC Article
Giannoccaro MP, Matteo E, Bartiromo F, Tonon C, Santorelli FM, Liguori R, Rizzo G
Neurol Sci 2022 Sep;43(9):5501-5511. Epub 2022 May 21 doi: 10.1007/s10072-022-06145-1. PMID: 35595875

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