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Hereditary spastic paraplegia 61(SPG61)

MedGen UID:
816624
•Concept ID:
C3810294
•
Disease or Syndrome
Synonym: Spastic paraplegia 61, autosomal recessive
SNOMED CT: Autosomal recessive spastic paraplegia type 61 (726611001)
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).
Autosomal recessive inheritance (Orphanet)
 
Gene (location): ARL6IP1 (16p12.3)
 
Monarch Initiative: MONDO:0014304
OMIM®: 615685
Orphanet: ORPHA401780

Definition

A rare complex form of hereditary spastic paraplegia with characteristics of onset in infancy of spastic paraplegia (presenting with the inability to walk unsupported and a scissors gait) associated with a motor and sensory polyneuropathy with loss of terminal digits and acropathy. SPG61 is due to a mutation in the ARL6IP1 gene (16p12-p11.2) encoding the ADP-ribosylation factor-like protein 6-interacting protein 1. [from SNOMEDCT_US]

Clinical features

From HPO
Absent Achilles reflex
MedGen UID:
108240
•Concept ID:
C0558845
•
Finding
Absence of the Achilles reflex (also known as the ankle jerk reflex), which can normally be elicited by tapping the tendon is tapped while the foot is dorsiflexed.
See: Feature record | Search on this feature
Spasticity
MedGen UID:
7753
•Concept ID:
C0026838
•
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
See: Feature record | Search on this feature
Spastic paraplegia
MedGen UID:
20882
•Concept ID:
C0037772
•
Disease or Syndrome
Spasticity and weakness of the leg and hip muscles.
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Sensory neuropathy
MedGen UID:
101791
•Concept ID:
C0151313
•
Disease or Syndrome
Peripheral neuropathy affecting the sensory nerves.
See: Feature record | Search on this feature
Scissor gait
MedGen UID:
68547
•Concept ID:
C0231698
•
Finding
A type of spastic paraparetic gait in which the muscle tone in the adductors is marked. It is characterized by hypertonia and flexion in the legs, hips and pelvis accompanied by extreme adduction leading to the knees and thighs hitting, or sometimes even crossing, in a scissors-like movement. The opposing muscles (abductors) become comparatively weak from lack of use.
See: Feature record | Search on this feature
Hyperactive patellar reflex
MedGen UID:
66003
•Concept ID:
C0240116
•
Finding
See: Feature record | Search on this feature
Motor polyneuropathy
MedGen UID:
82885
•Concept ID:
C0271683
•
Disease or Syndrome
Inflammation or degeneration of the peripheral motor nerves.
See: Feature record | Search on this feature
Inability to walk
MedGen UID:
107860
•Concept ID:
C0560046
•
Finding
Incapability to ambulate.
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature
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Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary spastic paraplegia 61
Follow this link to review classifications for Hereditary spastic paraplegia 61 in Orphanet.

Recent clinical studies

Etiology

Hereditary spastic paraplegia: Genetic heterogeneity and common pathways.
Panza E, Meyyazhagan A, Orlacchio A
Exp Neurol 2022 Nov;357:114203. Epub 2022 Aug 13 doi: 10.1016/j.expneurol.2022.114203. PMID: 35970204
AP4B1-associated hereditary spastic paraplegia: expansion of phenotypic spectrum related to homozygous p.Thr387fs variant.
Szczałuba K, Mierzewska H, Śmigiel R, Kosińska J, Koppolu A, Biernacka A, Stawiński P, Pollak A, Rydzanicz M, Płoski R
J Appl Genet 2020 May;61(2):213-218. Epub 2020 Mar 12 doi: 10.1007/s13353-020-00552-w. PMID: 32166732Free PMC Article
Mutation analysis of CAPN1 in Chinese populations with spastic paraplegia and related neurodegenerative diseases.
Xia ZC, Liu ZH, Zhou XX, Liu Z, Wang JL, Hu ZM, Tan JQ, Shen L, Jiang H, Tang BS, Lei LF
J Neurol Sci 2020 Apr 15;411:116691. Epub 2020 Jan 18 doi: 10.1016/j.jns.2020.116691. PMID: 31982778
Locomotor coordination in patients with Hereditary Spastic Paraplegia.
Martino G, Ivanenko Y, Serrao M, Ranavolo A, Draicchio F, Casali C, Lacquaniti F
J Electromyogr Kinesiol 2019 Apr;45:61-69. Epub 2019 Feb 19 doi: 10.1016/j.jelekin.2019.02.006. PMID: 30836301
Targeted next-generation sequencing improves diagnosis of hereditary spastic paraplegia in Chinese patients.
Lu C, Li LX, Dong HL, Wei Q, Liu ZJ, Ni W, Gitler AD, Wu ZY
J Mol Med (Berl) 2018 Jul;96(7):701-712. Epub 2018 Jun 11 doi: 10.1007/s00109-018-1655-4. PMID: 29934652

Diagnosis

Deep Intronic FGF14 GAA Repeat Expansion in Late-Onset Cerebellar Ataxia.
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
The clinical and molecular spectrum of ZFYVE26-associated hereditary spastic paraplegia: SPG15.
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
Hereditary spastic paraplegia: Genetic heterogeneity and common pathways.
Panza E, Meyyazhagan A, Orlacchio A
Exp Neurol 2022 Nov;357:114203. Epub 2022 Aug 13 doi: 10.1016/j.expneurol.2022.114203. PMID: 35970204
Targeted next-generation sequencing improves diagnosis of hereditary spastic paraplegia in Chinese patients.
Lu C, Li LX, Dong HL, Wei Q, Liu ZJ, Ni W, Gitler AD, Wu ZY
J Mol Med (Berl) 2018 Jul;96(7):701-712. Epub 2018 Jun 11 doi: 10.1007/s00109-018-1655-4. PMID: 29934652
Pelizaeus-Merzbacher disease.
Koeppen AH, Robitaille Y
J Neuropathol Exp Neurol 2002 Sep;61(9):747-59. doi: 10.1093/jnen/61.9.747. PMID: 12230321

Therapy

The clinical and molecular spectrum of ZFYVE26-associated hereditary spastic paraplegia: SPG15.
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
The clinical effect of the GABA-agonist, progabide, on spasticity.
Mondrup K, Pedersen E
Acta Neurol Scand 1984 Apr;69(4):200-6. doi: 10.1111/j.1600-0404.1984.tb07802.x. PMID: 6377802

Prognosis

Mutation analysis of CAPN1 in Chinese populations with spastic paraplegia and related neurodegenerative diseases.
Xia ZC, Liu ZH, Zhou XX, Liu Z, Wang JL, Hu ZM, Tan JQ, Shen L, Jiang H, Tang BS, Lei LF
J Neurol Sci 2020 Apr 15;411:116691. Epub 2020 Jan 18 doi: 10.1016/j.jns.2020.116691. PMID: 31982778
Novel mutation in the SPG3A gene in an African American family with an early onset of hereditary spastic paraplegia.
Hedera P, Fenichel GM, Blair M, Haines JL
Arch Neurol 2004 Oct;61(10):1600-3. doi: 10.1001/archneur.61.10.1600. PMID: 15477516

Clinical prediction guides

The clinical and molecular spectrum of ZFYVE26-associated hereditary spastic paraplegia: SPG15.
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
Hereditary spastic paraplegia: Genetic heterogeneity and common pathways.
Panza E, Meyyazhagan A, Orlacchio A
Exp Neurol 2022 Nov;357:114203. Epub 2022 Aug 13 doi: 10.1016/j.expneurol.2022.114203. PMID: 35970204
Mutation analysis of CAPN1 in Chinese populations with spastic paraplegia and related neurodegenerative diseases.
Xia ZC, Liu ZH, Zhou XX, Liu Z, Wang JL, Hu ZM, Tan JQ, Shen L, Jiang H, Tang BS, Lei LF
J Neurol Sci 2020 Apr 15;411:116691. Epub 2020 Jan 18 doi: 10.1016/j.jns.2020.116691. PMID: 31982778
Carnitine palmitoyltransferase 1C: From cognition to cancer.
Casals N, Zammit V, Herrero L, Fadó R, Rodríguez-Rodríguez R, Serra D
Prog Lipid Res 2016 Jan;61:134-48. Epub 2015 Dec 18 doi: 10.1016/j.plipres.2015.11.004. PMID: 26708865
Autosomal dominant pure spastic paraplegia: a clinical, paraclinical, and genetic study.
Nielsen JE, Krabbe K, Jennum P, Koefoed P, Jensen LN, Fenger K, Eiberg H, Hasholt L, Werdelin L, Sørensen SA
J Neurol Neurosurg Psychiatry 1998 Jan;64(1):61-6. doi: 10.1136/jnnp.64.1.61. PMID: 9436729Free PMC Article

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    • ClinVar
      Related medical variations
    • Gene
      Related information in NCBI Gene
    • GTR
      Related information in GTR
    • GTR(Clinical)
      Clinical tests in GTR
    • OMIM
      Related records in OMIM
    • OMIM(Genes)
      OMIM records containing genes associated with phenotypes registered in MedGen
    • PMC Articles
      Related information in PubMed Central Links
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