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Hereditary spastic paraplegia 28(SPG28)

MedGen UID:
332174
Concept ID:
C1836295
Disease or Syndrome
Synonym: Spastic paraplegia 28, autosomal recessive
SNOMED CT: Autosomal recessive spastic paraplegia type 28 (763376002)
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): DDHD1 (14q22.1)
 
Monarch Initiative: MONDO:0012256
OMIM®: 609340
Orphanet: ORPHA101008

Definition

Spastic paraplegia-29 (SPG28) is an autosomal recessive neurodegenerative disorder characterized by early-onset, slowly progressive lower-limb spasticity resulting in walking difficulties. Some patients also have distal sensory impairment (summary by Tesson et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see 270800. [from OMIM]

Clinical features

From HPO
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight).
Lower limb muscle weakness
MedGen UID:
324478
Concept ID:
C1836296
Finding
Weakness of the muscles of the legs.
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.
Peripheral axonal neuropathy
MedGen UID:
266071
Concept ID:
C1263857
Disease or Syndrome
An abnormality characterized by disruption of the normal functioning of peripheral axons.
Lower limb spasticity
MedGen UID:
220865
Concept ID:
C1271100
Finding
Spasticity (velocity-dependent increase in tonic stretch reflexes with increased muscle tone and hyperexcitable tendon reflexes) in the muscles of the lower limbs, hips, and pelvis
Distal sensory impairment
MedGen UID:
335722
Concept ID:
C1847584
Finding
An abnormal reduction in sensation in the distal portions of the extremities.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Difficulty walking
MedGen UID:
86319
Concept ID:
C0311394
Finding
Reduced ability to walk (ambulate).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary spastic paraplegia 28
Follow this link to review classifications for Hereditary spastic paraplegia 28 in Orphanet.

Professional guidelines

PubMed

Zaghloul A, Manoukian D, Barrett MC, Geronta I, Maizen C
J Pediatr Orthop 2021 Oct 1;41(9):559-565. doi: 10.1097/BPO.0000000000001942. PMID: 34387232
Kerstens HCJW, Van Lith BJH, Nijkrake MJ, De Swart BJM, Van den Bemd LAC, Smeets RJEM, Klemens F, Van de Warrenburg BPC, Van der Wees PJ, Geurts ACH
Orphanet J Rare Dis 2021 Jun 24;16(1):283. doi: 10.1186/s13023-021-01915-0. PMID: 34167574Free PMC Article
Bettencourt C, Quintáns B, Ros R, Ampuero I, Yáñez Z, Pascual SI, de Yébenes JG, Sobrido MJ
Hum Mutat 2012 Sep;33(9):1315-23. Epub 2012 Jul 16 doi: 10.1002/humu.22148. PMID: 22753388

Recent clinical studies

Etiology

Jacinto-Scudeiro LA, Rothe-Neves R, Dos Santos VB, Machado GD, Burguêz D, Padovani MMP, Ayres A, Rech RS, González-Salazar C, Junior MCF, Saute JAM, Olchik MR
Clinics (Sao Paulo) 2023;78:100128. Epub 2022 Dec 3 doi: 10.1016/j.clinsp.2022.100128. PMID: 36473366Free PMC Article
Morsy H, Benkirane M, Cali E, Rocca C, Zhelcheska K, Cipriani V, Galanaki E, Maroofian R, Efthymiou S, Murphy D, O'Driscoll M, Suri M, Banka S, Clayton-Smith J, Wright T, Redman M, Bassetti JA, Nizon M, Cogne B, Jamra RA, Bartolomaeus T, Heruth M, Krey I, Gburek-Augustat J, Wieczorek D, Gattermann F, Mcentagart M, Goldenberg A, Guyant-Marechal L, Garcia-Moreno H, Giunti P, Chabrol B, Bacrot S, Buissonnière R, Magry V, Gowda VK, Srinivasan VM, Melegh B, Szabó A, Sümegi K, Cossée M, Ziff M, Butterfield R, Hunt D, Bird-Lieberman G, Hanna M, Koenig M, Stankewich M, Vandrovcova J, Houlden H; Genomics England Research Consortium
Genet Med 2023 Jan;25(1):76-89. Epub 2022 Nov 4 doi: 10.1016/j.gim.2022.09.013. PMID: 36331550Free 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
Giordani GM, Diniz F, Fussiger H, Gonzalez-Salazar C, Donis KC, Freua F, Ortega RPM, de Freitas JL, Barsottini OGP, Rosemberg S, Kok F, Pedroso JL, França MC Jr, Saute JAM
Sci Rep 2021 Nov 15;11(1):22248. doi: 10.1038/s41598-021-01635-2. PMID: 34782662Free 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

Diagnosis

Siow SF, Yeow D, Rudaks LI, Jia F, Wali G, Sue CM, Kumar KR
Genes (Basel) 2023 Sep 3;14(9) doi: 10.3390/genes14091756. PMID: 37761896Free PMC Article
Jacinto-Scudeiro LA, Rothe-Neves R, Dos Santos VB, Machado GD, Burguêz D, Padovani MMP, Ayres A, Rech RS, González-Salazar C, Junior MCF, Saute JAM, Olchik MR
Clinics (Sao Paulo) 2023;78:100128. Epub 2022 Dec 3 doi: 10.1016/j.clinsp.2022.100128. PMID: 36473366Free PMC Article
Laßmann C, Ilg W, Schneider M, Völker M, Haeufle DFB, Schüle R, Giese M, Synofzik M, Schöls L, Rattay TW
Mov Disord 2022 Dec;37(12):2417-2426. Epub 2022 Aug 29 doi: 10.1002/mds.29199. PMID: 36054444
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
Du J
J Clin Neurosci 2021 Mar;85:67-71. Epub 2021 Jan 15 doi: 10.1016/j.jocn.2020.11.036. PMID: 33581793

Therapy

van de Venis L, van de Warrenburg BPC, Weerdesteyn V, van Lith BJH, Geurts ACH, Nonnekes J
Trials 2021 Jan 7;22(1):32. doi: 10.1186/s13063-020-04932-9. PMID: 33413555Free 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
Geva-Dayan K, Domenievitz D, Zahalka R, Fattal-Valevski A
J Child Neurol 2010 Aug;25(8):969-75. Epub 2010 Apr 20 doi: 10.1177/0883073809356037. PMID: 20406997

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
Chen J, Zhao Z, Shen H, Bing Q, Li N, Guo X, Hu J
BMC Neurol 2022 May 16;22(1):180. doi: 10.1186/s12883-022-02708-z. PMID: 35578252Free PMC Article
Liu N, Chen J, Xu C, Shi T, Li J
Hereditas 2019;156:28. Epub 2019 Aug 13 doi: 10.1186/s41065-019-0104-x. PMID: 31427910Free PMC Article
Haynes KB, Wimberly RL, VanPelt JM, Jo CH, Riccio AI, Delgado MR
J Pediatr Orthop 2018 Mar;38(3):152-156. doi: 10.1097/BPO.0000000000001115. PMID: 29309384
Yahalom G, Anikster Y, Huna-Baron R, Hoffmann C, Blumkin L, Lev D, Tsabari R, Nitsan Z, Lerman SF, Ben-Zeev B, Pode-Shakked B, Sofer S, Schweiger A, Lerman-Sagie T, Hassin-Baer S
J Neurol 2014 Dec;261(12):2275-82. Epub 2014 Sep 9 doi: 10.1007/s00415-014-7481-x. PMID: 25201222

Clinical prediction guides

Laßmann C, Ilg W, Schneider M, Völker M, Haeufle DFB, Schüle R, Giese M, Synofzik M, Schöls L, Rattay TW
Mov Disord 2022 Dec;37(12):2417-2426. Epub 2022 Aug 29 doi: 10.1002/mds.29199. PMID: 36054444
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
Du J
J Clin Neurosci 2021 Mar;85:67-71. Epub 2021 Jan 15 doi: 10.1016/j.jocn.2020.11.036. PMID: 33581793
Liu N, Chen J, Xu C, Shi T, Li J
Hereditas 2019;156:28. Epub 2019 Aug 13 doi: 10.1186/s41065-019-0104-x. PMID: 31427910Free PMC Article
Yogev Y, Perez Y, Noyman I, Madegem AA, Flusser H, Shorer Z, Cohen E, Kachko L, Michaelovsky A, Birk R, Koifman A, Drabkin M, Wormser O, Halperin D, Kadir R, Birk OS
Eur J Hum Genet 2017 Aug;25(8):966-972. Epub 2017 May 10 doi: 10.1038/ejhg.2017.85. PMID: 28488683Free PMC Article

Recent systematic reviews

Vecchia SD, Tessa A, Dosi C, Baldacci J, Pasquariello R, Antenora A, Astrea G, Bassi MT, Battini R, Casali C, Cioffi E, Conti G, De Michele G, Ferrari AR, Filla A, Fiorillo C, Fusco C, Gallone S, Germiniasi C, Guerrini R, Haggiag S, Lopergolo D, Martinuzzi A, Melani F, Mignarri A, Panzeri E, Pini A, Pinto AM, Pochiero F, Primiano G, Procopio E, Renieri A, Romaniello R, Sancricca C, Servidei S, Spagnoli C, Ticci C, Rubegni A, Santorelli FM
J Neurol 2022 Jan;269(1):437-450. Epub 2021 Sep 6 doi: 10.1007/s00415-021-10792-3. PMID: 34487232
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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