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Hereditary sensory and autonomic neuropathy with spastic paraplegia

MedGen UID:
342492
Concept ID:
C1850395
Disease or Syndrome
Synonyms: Autosomal Recessive Sensory Neuropathy with Spastic Paraplegia; Neuropathy, hereditary sensory, with spastic paraplegia, autosomal recessive
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): CCT5 (5p15.2)
 
Monarch Initiative: MONDO:0009748
OMIM®: 256840
Orphanet: ORPHA139578

Definition

This syndrome is characterized by the association of an axonal sensory and autonomic neuropathy with spastic paraplegia. [from ORDO]

Clinical features

From HPO
Abnormal foot morphology
MedGen UID:
1762829
Concept ID:
C5399834
Anatomical Abnormality
An abnormality of the skeleton of foot.
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.
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.
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
Atrophy of the spinal cord
MedGen UID:
235592
Concept ID:
C1389102
Disease or Syndrome
Distal sensory impairment of all modalities
MedGen UID:
322937
Concept ID:
C1836527
Finding
Reduced ability to sense pain, temperature, touch, vibration stimuli in the distal regions of the extremities.
Distal sensory impairment
MedGen UID:
335722
Concept ID:
C1847584
Finding
An abnormal reduction in sensation in the distal portions of the extremities.
Decreased motor nerve conduction velocity
MedGen UID:
388130
Concept ID:
C1858729
Finding
A type of decreased nerve conduction velocity that affects the motor neuron.
Decreased amplitude of sensory action potentials
MedGen UID:
870496
Concept ID:
C4024943
Finding
A reduction in the amplitude of sensory nerve action potential. This feature is measured by nerve conduction studies.
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Foot osteomyelitis
MedGen UID:
1370023
Concept ID:
C4049342
Disease or Syndrome
An infection of bone of the foot.
Hypotriglyceridemia
MedGen UID:
488913
Concept ID:
C0542037
Disease or Syndrome
An decrease in the level of triglycerides in the blood.
Decreased circulating apolipoprotein B concentration
MedGen UID:
1814242
Concept ID:
C5676671
Finding
Reduced circulating level of apolipoprotein B, which is the main apolipoprotein of chylomicrons and low density lipoproteins. It occurs in plasma as two main isoforms, apoB-48 and apoB-100.
Acral ulceration
MedGen UID:
1648438
Concept ID:
C4732740
Finding
A type of digital ulcer that manifests as an open sore on the surface of the skin at the tip of a finger or toe.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary sensory and autonomic neuropathy with spastic paraplegia
Follow this link to review classifications for Hereditary sensory and autonomic neuropathy with spastic paraplegia in Orphanet.

Recent clinical studies

Etiology

Paprocka J, Jezela-Stanek A, Śmigiel R, Walczak A, Mierzewska H, Kutkowska-Kaźmierczak A, Płoski R, Emich-Widera E, Steinborn B
Genes (Basel) 2023 Apr 25;14(5) doi: 10.3390/genes14050972. PMID: 37239332Free 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
Toft A, Birk S, Ballegaard M, Dunø M, Hjermind LE, Nielsen JE, Svenstrup K
J Neurol 2019 Mar;266(3):735-744. Epub 2019 Jan 12 doi: 10.1007/s00415-019-09196-1. PMID: 30637453
Vallat JM, Goizet C, Tazir M, Couratier P, Magy L, Mathis S
Rev Neurol (Paris) 2016 Jun-Jul;172(6-7):339-49. Epub 2016 May 27 doi: 10.1016/j.neurol.2016.04.005. PMID: 27240993
Timmerman V, Clowes VE, Reid E
Exp Neurol 2013 Aug;246:14-25. Epub 2012 Jan 18 doi: 10.1016/j.expneurol.2012.01.010. PMID: 22285450

Diagnosis

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
Stojkovic T
Rev Neurol (Paris) 2016 Dec;172(12):775-778. Epub 2016 Nov 17 doi: 10.1016/j.neurol.2016.06.007. PMID: 27866730
Vallat JM, Goizet C, Tazir M, Couratier P, Magy L, Mathis S
Rev Neurol (Paris) 2016 Jun-Jul;172(6-7):339-49. Epub 2016 May 27 doi: 10.1016/j.neurol.2016.04.005. PMID: 27240993
Lamari F, Mochel F, Sedel F, Saudubray JM
J Inherit Metab Dis 2013 May;36(3):411-25. Epub 2012 Jul 20 doi: 10.1007/s10545-012-9509-7. PMID: 22814679
Schady W, Smith CM
J Neurol Neurosurg Psychiatry 1994 Jun;57(6):693-8. doi: 10.1136/jnnp.57.6.693. PMID: 8006649Free PMC Article

Therapy

Yang H, Brown RH Jr, Wang D, Strauss KA, Gao G
Trends Mol Med 2021 Jun;27(6):520-523. Epub 2021 Mar 10 doi: 10.1016/j.molmed.2021.02.004. PMID: 33714697Free PMC Article
Rossier AB, Ziegler WH, Duchosal PW, Meylan J
Paraplegia 1971 May;9(1):51-63. doi: 10.1038/sc.1971.8. PMID: 5120042

Prognosis

Pareyson D, Saveri P, Sagnelli A, Piscosquito G
Neurosci Lett 2015 Jun 2;596:66-77. Epub 2015 Apr 3 doi: 10.1016/j.neulet.2015.04.001. PMID: 25847151
Ylikallio E, Kim D, Isohanni P, Auranen M, Kim E, Lönnqvist T, Tyynismaa H
Eur J Hum Genet 2015 Oct;23(10):1427-30. Epub 2015 Jan 14 doi: 10.1038/ejhg.2014.297. PMID: 25585697Free PMC Article
Klebe S, Lossos A, Azzedine H, Mundwiller E, Sheffer R, Gaussen M, Marelli C, Nawara M, Carpentier W, Meyer V, Rastetter A, Martin E, Bouteiller D, Orlando L, Gyapay G, El-Hachimi KH, Zimmerman B, Gamliel M, Misk A, Lerer I, Brice A, Durr A, Stevanin G
Eur J Hum Genet 2012 Jun;20(6):645-9. Epub 2012 Jan 18 doi: 10.1038/ejhg.2011.261. PMID: 22258533Free PMC Article
Schady W, Smith CM
J Neurol Neurosurg Psychiatry 1994 Jun;57(6):693-8. doi: 10.1136/jnnp.57.6.693. PMID: 8006649Free PMC Article

Clinical prediction guides

Paprocka J, Jezela-Stanek A, Śmigiel R, Walczak A, Mierzewska H, Kutkowska-Kaźmierczak A, Płoski R, Emich-Widera E, Steinborn B
Genes (Basel) 2023 Apr 25;14(5) doi: 10.3390/genes14050972. PMID: 37239332Free PMC Article
Tamim-Yecheskel BC, Fraiberg M, Kokabi K, Freud S, Shatz O, Marvaldi L, Subic N, Brenner O, Tsoory M, Eilam-Altstadter R, Biton I, Savidor A, Dezorella N, Heimer G, Behrends C, Ben-Zeev B, Elazar Z
Autophagy 2021 Oct;17(10):3082-3095. Epub 2020 Dec 10 doi: 10.1080/15548627.2020.1852724. PMID: 33218264Free PMC Article
Leonardis L, Auer-Grumbach M, Papić L, Zidar J
Eur J Neurol 2012 Jul;19(7):992-8. Epub 2012 Feb 16 doi: 10.1111/j.1468-1331.2012.03665.x. PMID: 22340599
Klebe S, Azzedine H, Durr A, Bastien P, Bouslam N, Elleuch N, Forlani S, Charon C, Koenig M, Melki J, Brice A, Stevanin G
Brain 2006 Jun;129(Pt 6):1456-62. Epub 2006 Jan 24 doi: 10.1093/brain/awl012. PMID: 16434418
Bouhouche A, Benomar A, Bouslam N, Ouazzani R, Chkili T, Yahyaoui M
Eur J Hum Genet 2006 Feb;14(2):249-52. doi: 10.1038/sj.ejhg.5201537. PMID: 16333315

Recent systematic reviews

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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