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Hereditary spastic paraplegia 18(SPG18B)

MedGen UID:
442343
Concept ID:
C2749936
Disease or Syndrome
Synonyms: INTELLECTUAL DISABILITY, MOTOR DYSFUNCTION, AND JOINT CONTRACTURES; Spastic paraplegia 18; SPASTIC PARAPLEGIA 18, AUTOSOMAL RECESSIVE; SPASTIC PARAPLEGIA 18B, AUTOSOMAL RECESSIVE; SPG18B
SNOMED CT: Autosomal recessive spastic paraplegia type 18 (732932004)
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): ERLIN2 (8p11.23)
 
Monarch Initiative: MONDO:0012639
OMIM®: 611225
Orphanet: ORPHA209951

Definition

Spastic paraplegia-18B (SPG18B) is a severe autosomal recessive neurologic disorder characterized by onset in early childhood of progressive spastic paraplegia resulting in motor disability. Most affected individuals have severe psychomotor retardation. Some may develop significant joint contractures (summary by Alazami et al., 2011 and Yildirim et al., 2011). [from OMIM]

Clinical features

From HPO
Ankle clonus
MedGen UID:
68672
Concept ID:
C0238651
Finding
Clonus is an involuntary tendon reflex that causes repeated flexion and extension of the foot. Ankle clonus is tested by rapidly flexing the foot upward.
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.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
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.
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.
Inability to walk
MedGen UID:
107860
Concept ID:
C0560046
Finding
Incapability to ambulate.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
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.
Upper limb spasticity
MedGen UID:
220882
Concept ID:
C1273957
Finding
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
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.
Biceps hyperreflexia
MedGen UID:
1764189
Concept ID:
C5421682
Finding
Increased intensity of the biceps reflex.
Joint contracture
MedGen UID:
3228
Concept ID:
C0009918
Anatomical Abnormality
A limitation in the passive range of motion of a joint resulting from loss of elasticity in the periarticular tissues owing to structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules or skin. A contracture prevents movement of the associated body part.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary spastic paraplegia 18
Follow this link to review classifications for Hereditary spastic paraplegia 18 in Orphanet.

Professional guidelines

PubMed

Vogel AP, Graf LH, Magee M, Schöls L, Rommel N, Synofzik M
Ann Clin Transl Neurol 2022 Aug;9(8):1310-1315. Epub 2022 Jun 21 doi: 10.1002/acn3.51613. PMID: 35726838Free PMC Article
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
Erfanian Omidvar M, Torkamandi S, Rezaei S, Alipoor B, Omrani MD, Darvish H, Ghaedi H
J Neurol 2021 Jun;268(6):2065-2082. Epub 2019 Nov 19 doi: 10.1007/s00415-019-09633-1. PMID: 31745725

Recent clinical studies

Etiology

Méreaux JL, Davoine CS, Pellerin D, Coarelli G, Coutelier M, Ewenczyk C, Monin ML, Anheim M, Le Ber I, Thobois S, Gobert F, Guillot-Noël L, Forlani S, Jornea L, Heinzmann A, Sangare A, Gaymard B, Guyant-Maréchal L, Charles P, Marelli C, Honnorat J, Degos B, Tison F, Sangla S, Simonetta-Moreau M, Salachas F, Tchikviladzé M, Castelnovo G, Mochel F, Klebe S, Castrioto A, Fenu S, Méneret A, Bourdain F, Wandzel M, Roth V, Bonnet C, Riant F, Stevanin G, Noël S, Fauret-Amsellem AL, Bahlo M, Lockhart PJ, Brais B, Renaud M, Brice A, Durr A
EBioMedicine 2024 Jan;99:104931. Epub 2023 Dec 27 doi: 10.1016/j.ebiom.2023.104931. PMID: 38150853Free PMC Article
Murala S, Nagarajan E, Bollu PC
Neurol Sci 2021 Mar;42(3):883-894. Epub 2021 Jan 13 doi: 10.1007/s10072-020-04981-7. PMID: 33439395
Shribman S, Reid E, Crosby AH, Houlden H, Warner TT
Lancet Neurol 2019 Dec;18(12):1136-1146. Epub 2019 Jul 31 doi: 10.1016/S1474-4422(19)30235-2. PMID: 31377012
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320
Novarino G, Fenstermaker AG, Zaki MS, Hofree M, Silhavy JL, Heiberg AD, Abdellateef M, Rosti B, Scott E, Mansour L, Masri A, Kayserili H, Al-Aama JY, Abdel-Salam GMH, Karminejad A, Kara M, Kara B, Bozorgmehri B, Ben-Omran T, Mojahedi F, El Din Mahmoud IG, Bouslam N, Bouhouche A, Benomar A, Hanein S, Raymond L, Forlani S, Mascaro M, Selim L, Shehata N, Al-Allawi N, Bindu PS, Azam M, Gunel M, Caglayan A, Bilguvar K, Tolun A, Issa MY, Schroth J, Spencer EG, Rosti RO, Akizu N, Vaux KK, Johansen A, Koh AA, Megahed H, Durr A, Brice A, Stevanin G, Gabriel SB, Ideker T, Gleeson JG
Science 2014 Jan 31;343(6170):506-511. doi: 10.1126/science.1247363. PMID: 24482476Free PMC Article

Diagnosis

Pellerin D, Danzi MC, Wilke C, Renaud M, Fazal S, Dicaire MJ, Scriba CK, Ashton C, Yanick C, Beijer D, Rebelo A, Rocca C, Jaunmuktane Z, Sonnen JA, Larivière R, Genís D, Molina Porcel L, Choquet K, Sakalla R, Provost S, Robertson R, Allard-Chamard X, Tétreault M, Reiling SJ, Nagy S, Nishadham V, Purushottam M, Vengalil S, Bardhan M, Nalini A, Chen Z, Mathieu J, Massie R, Chalk CH, Lafontaine AL, Evoy F, Rioux MF, Ragoussis J, Boycott KM, Dubé MP, Duquette A, Houlden H, Ravenscroft G, Laing NG, Lamont PJ, Saporta MA, Schüle R, Schöls L, La Piana R, Synofzik M, Zuchner S, Brais B
N Engl J Med 2023 Jan 12;388(2):128-141. Epub 2022 Dec 14 doi: 10.1056/NEJMoa2207406. PMID: 36516086Free PMC Article
Murala S, Nagarajan E, Bollu PC
Neurol Sci 2021 Mar;42(3):883-894. Epub 2021 Jan 13 doi: 10.1007/s10072-020-04981-7. PMID: 33439395
Shribman S, Reid E, Crosby AH, Houlden H, Warner TT
Lancet Neurol 2019 Dec;18(12):1136-1146. Epub 2019 Jul 31 doi: 10.1016/S1474-4422(19)30235-2. PMID: 31377012
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320
Novarino G, Fenstermaker AG, Zaki MS, Hofree M, Silhavy JL, Heiberg AD, Abdellateef M, Rosti B, Scott E, Mansour L, Masri A, Kayserili H, Al-Aama JY, Abdel-Salam GMH, Karminejad A, Kara M, Kara B, Bozorgmehri B, Ben-Omran T, Mojahedi F, El Din Mahmoud IG, Bouslam N, Bouhouche A, Benomar A, Hanein S, Raymond L, Forlani S, Mascaro M, Selim L, Shehata N, Al-Allawi N, Bindu PS, Azam M, Gunel M, Caglayan A, Bilguvar K, Tolun A, Issa MY, Schroth J, Spencer EG, Rosti RO, Akizu N, Vaux KK, Johansen A, Koh AA, Megahed H, Durr A, Brice A, Stevanin G, Gabriel SB, Ideker T, Gleeson JG
Science 2014 Jan 31;343(6170):506-511. doi: 10.1126/science.1247363. PMID: 24482476Free PMC Article

Therapy

Mou Y, Nandi G, Mukte S, Chai E, Chen Z, Nielsen JE, Nielsen TT, Criscuolo C, Blackstone C, Fraidakis MJ, Li XJ
Orphanet J Rare Dis 2023 Apr 6;18(1):72. doi: 10.1186/s13023-023-02666-w. PMID: 37024986Free PMC Article
van de Venis L, van de Warrenburg B, Weerdesteyn V, Geurts ACH, Nonnekes J
Neurorehabil Neural Repair 2023 Jan;37(1):27-36. Epub 2023 Jan 25 doi: 10.1177/15459683221147839. PMID: 36695288Free PMC Article
Saffari A, Kellner M, Jordan C, Rosengarten H, Mo A, Zhang B, Strelko O, Neuser S, Davis MY, Yoshikura N, Futamura N, Takeuchi T, Nabatame S, Ishiura H, Tsuji S, Aldeen HS, Cali E, Rocca C, Houlden H, Efthymiou S, Assmann B, Yoon G, Trombetta BA, Kivisäkk P, Eichler F, Nan H, Takiyama Y, Tessa A, Santorelli FM, Sahin M, Blackstone C, Yang E, Schüle R, Ebrahimi-Fakhari D
Brain 2023 May 2;146(5):2003-2015. doi: 10.1093/brain/awac391. PMID: 36315648Free PMC Article
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Arq Neuropsiquiatr 2018 Mar;76(3):183-188. doi: 10.1590/0004-282x20180013. PMID: 29809239
Growdon JH, Nader TM, Schoenfeld J, Wurtman RJ
Clin Neuropharmacol 1991 Oct;14(5):403-12. doi: 10.1097/00002826-199110000-00003. PMID: 1742749

Prognosis

Alecu JE, Saffari A, Jumo H, Ziegler M, Strelko O, Brownstein CA, Gonzalez-Heydrich J, Rodan LH, Gorman MP, Sahin M, Ebrahimi-Fakhari D
Ann Clin Transl Neurol 2022 Apr;9(4):570-576. Epub 2022 Mar 16 doi: 10.1002/acn3.51531. PMID: 35297214Free PMC Article
Cubillos-Arcila DM, Machado GD, Sehnem L, Burguêz D, Zanardi APJ, Martins VF, Peyré-Tartaruga LA, Saute JAM
Cerebellum 2022 Jun;21(3):350-357. Epub 2021 Jul 9 doi: 10.1007/s12311-021-01302-2. PMID: 34244902
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
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
Wakil SM, Murad HN, Baz BM, Hagos ST, Al-Amr RA, Al-Yamani SA, Al-Wadaee SM, Meyer BF, Bohlega SA
Neurosciences (Riyadh) 2012 Jan;17(1):48-52. PMID: 22246010

Clinical prediction guides

Kilic MA, Yildiz EP, Deniz A, Coskun O, Kurekci F, Avci R, Genc HM, Yesil G, Akbas S, Yesilyurt A, Kara B
Pediatr Neurol 2024 Mar;152:189-195. Epub 2024 Jan 6 doi: 10.1016/j.pediatrneurol.2024.01.005. PMID: 38301322
Méreaux JL, Davoine CS, Pellerin D, Coarelli G, Coutelier M, Ewenczyk C, Monin ML, Anheim M, Le Ber I, Thobois S, Gobert F, Guillot-Noël L, Forlani S, Jornea L, Heinzmann A, Sangare A, Gaymard B, Guyant-Maréchal L, Charles P, Marelli C, Honnorat J, Degos B, Tison F, Sangla S, Simonetta-Moreau M, Salachas F, Tchikviladzé M, Castelnovo G, Mochel F, Klebe S, Castrioto A, Fenu S, Méneret A, Bourdain F, Wandzel M, Roth V, Bonnet C, Riant F, Stevanin G, Noël S, Fauret-Amsellem AL, Bahlo M, Lockhart PJ, Brais B, Renaud M, Brice A, Durr A
EBioMedicine 2024 Jan;99:104931. Epub 2023 Dec 27 doi: 10.1016/j.ebiom.2023.104931. PMID: 38150853Free PMC Article
Saffari A, Kellner M, Jordan C, Rosengarten H, Mo A, Zhang B, Strelko O, Neuser S, Davis MY, Yoshikura N, Futamura N, Takeuchi T, Nabatame S, Ishiura H, Tsuji S, Aldeen HS, Cali E, Rocca C, Houlden H, Efthymiou S, Assmann B, Yoon G, Trombetta BA, Kivisäkk P, Eichler F, Nan H, Takiyama Y, Tessa A, Santorelli FM, Sahin M, Blackstone C, Yang E, Schüle R, Ebrahimi-Fakhari D
Brain 2023 May 2;146(5):2003-2015. doi: 10.1093/brain/awac391. PMID: 36315648Free PMC Article
Navas-Sánchez FJ, Fernández-Pena A, Martín de Blas D, Alemán-Gómez Y, Marcos-Vidal L, Guzmán-de-Villoria JA, Fernández-García P, Romero J, Catalina I, Lillo L, Muñoz-Blanco JL, Ordoñez-Ugalde A, Quintáns B, Pardo J, Sobrido MJ, Carmona S, Grandas F, Desco M
J Neurol 2021 Jul;268(7):2429-2440. Epub 2021 Jan 28 doi: 10.1007/s00415-020-10387-4. PMID: 33507371
González-Salazar C, Takazaki KAG, Martinez ARM, Pimentel-Silva LR, Jacinto-Scudeiro LA, Nakagawa ÉY, Fujiwara Murakami CE, Saute JAM, Pedroso JL, Barsottini OGP, Teive HAG, França MC Jr
Eur J Neurol 2019 Apr;26(4):687-693. Epub 2019 Jan 10 doi: 10.1111/ene.13878. PMID: 30489674

Recent systematic reviews

Erfanian Omidvar M, Torkamandi S, Rezaei S, Alipoor B, Omrani MD, Darvish H, Ghaedi H
J Neurol 2021 Jun;268(6):2065-2082. Epub 2019 Nov 19 doi: 10.1007/s00415-019-09633-1. PMID: 31745725
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320

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