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Hereditary spastic paraplegia 17(SPG17)

MedGen UID:
419034
Concept ID:
C2931276
Disease or Syndrome
Synonyms: Autosomal dominant spastic paraplegia type 17; Silver spastic paraplegia syndrome; Silver Syndrome; Spastic paraplegia 17; Spastic paraplegia with amyotrophy of hands and feet
SNOMED CT: Silver disease (230263009); Autosomal dominant spastic paraplegia type 17 (230263009)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): BSCL2 (11q12.3)
 
Monarch Initiative: MONDO:0010043
OMIM®: 270685
Orphanet: ORPHA100998

Disease characteristics

The spectrum of BSCL2-related neurologic disorders includes Silver syndrome and variants of Charcot-Marie-Tooth neuropathy type 2, distal hereditary motor neuropathy (dHMN) type V, and spastic paraplegia 17. Features of these disorders include onset of symptoms ranging from the first to the seventh decade, slow disease progression, upper motor neuron involvement (gait disturbance with pyramidal signs ranging from mild to severe spasticity with hyperreflexia in the lower limbs and variable extensor plantar responses), lower motor neuron involvement (amyotrophy of the peroneal muscles and small muscles of the hand), and pes cavus and other foot deformities. Disease severity is variable among and within families. [from GeneReviews]
Authors:
Daisuke Ito   view full author information

Additional description

From MedlinePlus Genetics
The first sign of Silver syndrome is usually weakness in the muscles of the hands. These muscles waste away (amyotrophy), resulting in abnormal positioning of the thumbs and difficulty using the fingers and hands for tasks such as handwriting. People with Silver syndrome often have high-arched feet (pes cavus) and spasticity in the legs. The signs and symptoms of Silver syndrome typically begin in late childhood but can start anytime from early childhood to late adulthood. The muscle problems associated with Silver syndrome slowly worsen with age, but affected individuals can remain active throughout life.

Silver syndrome belongs to a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and, frequently, development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. Both types involve the lower limbs; the complex types may also involve the upper limbs, although to a lesser degree. In addition, the complex types may affect the brain and parts of the nervous system involved in muscle movement and sensations. Silver syndrome is a complex hereditary spastic paraplegia.  https://medlineplus.gov/genetics/condition/silver-syndrome

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).
Thenar muscle weakness
MedGen UID:
330427
Concept ID:
C1832276
Finding
Lower limb muscle weakness
MedGen UID:
324478
Concept ID:
C1836296
Finding
Weakness of the muscles of the legs.
Split hand
MedGen UID:
397570
Concept ID:
C2699510
Congenital Abnormality
A condition in which middle parts of the hand (fingers and metacarpals) are missing giving a cleft appearance. The severity is very variable ranging from slightly hypoplastic middle fingers over absent middel fingers as far as oligo- or monodactyl hands.
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.
Postural tremor
MedGen UID:
66696
Concept ID:
C0234378
Sign or Symptom
A type of tremors that is triggered by holding a limb in a fixed position.
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
Impaired vibration sensation in the lower limbs
MedGen UID:
338617
Concept ID:
C1849134
Finding
A decrease in the ability to perceive vibration in the legs.
Decreased motor nerve conduction velocity
MedGen UID:
388130
Concept ID:
C1858729
Finding
A type of decreased nerve conduction velocity that affects the motor neuron.
Impaired distal tactile sensation
MedGen UID:
867225
Concept ID:
C4021583
Finding
A reduced sense of touch (tactile sensation) on the skin of the distal limbs. This is usually tested with a wisp of cotton or a fine camel's hair brush, by asking patients to say 'now' each time they feel the stimulus.
Impaired distal proprioception
MedGen UID:
867227
Concept ID:
C4021585
Finding
A loss or impairment of the sensation of the relative position of parts of the body and joint position occuring at distal joints.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
First dorsal interossei muscle weakness
MedGen UID:
371289
Concept ID:
C1832277
Finding
First dorsal interossei muscle atrophy
MedGen UID:
371290
Concept ID:
C1832278
Finding
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Thenar muscle atrophy
MedGen UID:
355274
Concept ID:
C1864715
Finding
Wasting of thenar muscles, which are located on palm of the hand at the base of the thumb.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary spastic paraplegia 17

Professional guidelines

PubMed

Gasser T, Finsterer J, Baets J, Van Broeckhoven C, Di Donato S, Fontaine B, De Jonghe P, Lossos A, Lynch T, Mariotti C, Schöls L, Spinazzola A, Szolnoki Z, Tabrizi SJ, Tallaksen CM, Zeviani M, Burgunder JM, Harbo HF; EFNS
Eur J Neurol 2010 Feb;17(2):179-88. Epub 2009 Dec 28 doi: 10.1111/j.1468-1331.2009.02873.x. PMID: 20050888

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
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
Narendiran S, Debnath M, Shivaram S, Kannan R, Sharma S, Christopher R, Seshagiri DV, Jain S, Purushottam M, Mangalore S, Bharath RD, Bindu PS, Sinha S, Taly AB, Nagappa M
J Neurogenet 2022 Mar;36(1):21-31. Epub 2022 May 2 doi: 10.1080/01677063.2022.2064463. PMID: 35499206
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
Servelhere KR, Casseb RF, de Lima FD, Rezende TJR, Ramalho LP, França MC Jr
AJNR Am J Neuroradiol 2021 Mar;42(3):610-615. Epub 2021 Jan 21 doi: 10.3174/ajnr.A7017. PMID: 33478946Free 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
Méreaux JL, Banneau G, Papin M, Coarelli G, Valter R, Raymond L, Kol B, Ariste O, Parodi L, Tissier L, Mairey M, Ait Said S, Gautier C, Guillaud-Bataille M; French SPATAX clinical network, Forlani S, de la Grange P, Brice A, Vazza G, Durr A, Leguern E, Stevanin G
Brain 2022 Apr 29;145(3):1029-1037. doi: 10.1093/brain/awab386. PMID: 34983064
Haj Salem I, Beaudin M, Stumpf M, Estiar MA, Côté PO, Brunet F, Gamache PL, Rouleau GA, Mourabit-Amari K, Gan-Or Z, Dupré N
Can J Neurol Sci 2021 Sep;48(5):655-665. Epub 2021 Jan 5 doi: 10.1017/cjn.2020.277. PMID: 33397523

Therapy

Diniz de Lima F, Faber I, Servelhere KR, Bittar MFR, Martinez ARM, Piovesana LG, Martins MP, Martins CR Jr, Benaglia T, de Sá Carvalho B, Nucci A, França MC Jr
Mov Disord 2021 Jul;36(7):1654-1663. Epub 2021 Feb 17 doi: 10.1002/mds.28523. PMID: 33595142
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
Margetis K, Korfias S, Boutos N, Gatzonis S, Themistocleous M, Siatouni A, Dalivigka Z, Flaskas T, Stranjalis G, Boviatsis E, Sakas D
Clin Neurol Neurosurg 2014 Aug;123:142-5. Epub 2014 Jun 4 doi: 10.1016/j.clineuro.2014.05.024. PMID: 24973568
Westhoff B, Seller K, Wild A, Jaeger M, Krauspe R
Dev Med Child Neurol 2003 Dec;45(12):829-32. doi: 10.1017/s0012162203001531. PMID: 14667075

Prognosis

Mahungu AC, Monnakgotla N, Nel M, Heckmann JM
Orphanet J Rare Dis 2022 Mar 24;17(1):133. doi: 10.1186/s13023-022-02280-2. PMID: 35331287Free PMC Article
Méreaux JL, Banneau G, Papin M, Coarelli G, Valter R, Raymond L, Kol B, Ariste O, Parodi L, Tissier L, Mairey M, Ait Said S, Gautier C, Guillaud-Bataille M; French SPATAX clinical network, Forlani S, de la Grange P, Brice A, Vazza G, Durr A, Leguern E, Stevanin G
Brain 2022 Apr 29;145(3):1029-1037. doi: 10.1093/brain/awab386. PMID: 34983064
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
Orsucci D, Petrucci L, Ienco EC, Chico L, Simi P, Fogli A, Baldinotti F, Simoncini C, LoGerfo A, Carlesi C, Arnoldi A, Bassi MT, Siciliano G, Bonuccelli U, Mancuso M
Clin Neurol Neurosurg 2014 May;120:14-9. Epub 2014 Feb 17 doi: 10.1016/j.clineuro.2014.02.002. PMID: 24731568
Racis L, Tessa A, Pugliatti M, Storti E, Agnetti V, Santorelli FM
Eur J Paediatr Neurol 2014 Mar;18(2):235-9. Epub 2013 Oct 9 doi: 10.1016/j.ejpn.2013.09.009. PMID: 24144828

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
Utz KS, Kohl Z, Marterstock DC, Doerfler A, Winkler J, Schmidt M, Regensburger M
Orphanet J Rare Dis 2022 Jul 29;17(1):301. doi: 10.1186/s13023-022-02451-1. PMID: 35906604Free PMC Article
Méreaux JL, Banneau G, Papin M, Coarelli G, Valter R, Raymond L, Kol B, Ariste O, Parodi L, Tissier L, Mairey M, Ait Said S, Gautier C, Guillaud-Bataille M; French SPATAX clinical network, Forlani S, de la Grange P, Brice A, Vazza G, Durr A, Leguern E, Stevanin G
Brain 2022 Apr 29;145(3):1029-1037. doi: 10.1093/brain/awab386. PMID: 34983064
Servelhere KR, Casseb RF, de Lima FD, Rezende TJR, Ramalho LP, França MC Jr
AJNR Am J Neuroradiol 2021 Mar;42(3):610-615. Epub 2021 Jan 21 doi: 10.3174/ajnr.A7017. PMID: 33478946Free PMC Article
Chou CT, Soong BW, Lin KP, Tsai YS, Jih KY, Liao YC, Lee YC
Ann Clin Transl Neurol 2020 Apr;7(4):486-496. Epub 2020 Mar 22 doi: 10.1002/acn3.51019. PMID: 32202070Free PMC Article

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
Neuser S, Brechmann B, Heimer G, Brösse I, Schubert S, O'Grady L, Zech M, Srivastava S, Sweetser DA, Dincer Y, Mall V, Winkelmann J, Behrends C, Darras BT, Graham RJ, Jayakar P, Byrne B, Bar-Aluma BE, Haberman Y, Szeinberg A, Aldhalaan HM, Hashem M, Al Tenaiji A, Ismayl O, Al Nuaimi AE, Maher K, Ibrahim S, Khan F, Houlden H, Ramakumaran VS, Pagnamenta AT, Posey JE, Lupski JR, Tan WH, ElGhazali G, Herman I, Muñoz T, Repetto GM, Seitz A, Krumbiegel M, Poli MC, Kini U, Efthymiou S, Meiler J, Maroofian R, Alkuraya FS, Abou Jamra R, Popp B, Ben-Zeev B, Ebrahimi-Fakhari D
Hum Mutat 2021 Jun;42(6):762-776. Epub 2021 May 11 doi: 10.1002/humu.24206. PMID: 33847017

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