# Paraplegia espástica hereditária

> Página oficial: https://raras.org/doenca/paraplegia-espastica-hereditaria
> Fonte: Raras.org — Banco de Dados de Doenças Raras em Português (CC BY-NC-SA 4.0)
> Última atualização: 2026-05-07

## Identificadores

- **ORPHA**: 685 — https://www.orpha.net/en/disease/detail/685
- **CID-10**: G11.4
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

As paraplegias espásticas hereditárias (PHS) compreendem um grupo genética e clinicamente heterogêneo de doenças neurodegenerativas caracterizadas por espasticidade progressiva e hiperreflexia dos membros inferiores.

## Epidemiologia e herança

- **Prevalência**: 1-9 / 100 000
- **Padrão de herança**: Autosomal dominant, Autosomal recessive, X-linked recessive

## Sinais e sintomas (694 fenótipos HPO)

- **Morfologia anormal da substância branca cerebral** — HPO: HP:0002500
- **Dificuldades alimentares na infância** — HPO: HP:0008872
- **Artralgia** — HPO: HP:0002829
- **Fraturas recorrentes** — HPO: HP:0002757
- **Fasciculações de membro** — HPO: HP:0007289
- **Fasciculações da língua** — HPO: HP:0001308
- **Aumento da densidade óssea espinhal** — HPO: HP:0004563
- **Dor óssea** — HPO: HP:0002653
- **Fraqueza muscular generalizada** — HPO: HP:0003324
- **Disinergia detrusor-esfincteriana** — HPO: HP:0025488
- **Anormalidade muscular relacionada à disfunção mitocondrial** — HPO: HP:0003800
- **Anormalidade da morfologia esquelética** — HPO: HP:0011842
- **Concentração elevada de fosfatase alcalina circulante** — HPO: HP:0003155
- **Criptorquidia bilateral** — HPO: HP:0008689
- **Displasia do quadril** — HPO: HP:0001385
- **Deformidade em equinovaro** — HPO: HP:0008110
- **Apneia episódica súbita** — HPO: HP:0002882
- **Disfagia neuromuscular** — HPO: HP:0002068
- **Controle cefálico pobre** — HPO: HP:0002421
- **Macrodontia do incisivo central superior permanente** — HPO: HP:0000675
- **Fraqueza devido à disfunção do neurônio motor superior** — HPO: HP:0010549
- **Distonia paroxística** — HPO: HP:0002268
- **Insônia** — HPO: HP:0100785
- **Mastigação prejudicada** — HPO: HP:0005216
- **Anormalidade no teste de visão de cores** — HPO: HP:0030584
- **Miocimia facial** — HPO: HP:0000317
- **Ataxia cerebelar progressiva** — HPO: HP:0002073
- **Bexiga neurogênica** — HPO: HP:0000011
- **Fadiga** — HPO: HP:0012378
- **Anomalia "olho de tigre" do globo pálido** — HPO: HP:0002454
- **Fácies em máscara** — HPO: HP:0000298
- **Transtorno do movimento extrapiramidal progressivo** — HPO: HP:0007153
- **Quadriplegia espástica progressiva** — HPO: HP:0002478
- **Transtorno afetivo bipolar** — HPO: HP:0007302
- **Anormalidade do canal auditivo** — HPO: HP:0000372
- **Displasia cortical** — HPO: HP:0002539
- **Distonia de membro** — HPO: HP:0002451
- **Amiotrofia da musculatura do tornozelo** — HPO: HP:0009031
- **Diminuição lenta da acuidade visual** — HPO: HP:0007924
- **Deformidade posicional do pé** — HPO: HP:0005656
- _...e mais 654 sintomas. Ver https://raras.org/doenca/paraplegia-espastica-hereditaria._

## Genes associados (67)

- **SPG21** — Maspardin [Disease-causing germline mutation(s) in]
  - Função: May play a role as a negative regulatory factor in CD4-dependent T-cell activation
- **ZFR** — Zinc finger RNA-binding protein [Candidate gene tested in]
  - Função: Involved in postimplantation and gastrulation stages of development. Involved in the nucleocytoplasmic shuttling of STAU2. Binds to DNA and RNA (By similarity)
- **CCT5** — T-complex protein 1 subunit epsilon [Candidate gene tested in]
  - Função: Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of actin, tubulin and other proteins upon ATP hydrolysis (PubMed:25467444, PubMed:364937
- **WASHC5** — WASH complex subunit 5 [Candidate gene tested in]
  - Função: Acts as a component of the WASH core complex that functions as a nucleation-promoting factor (NPF) at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polym
- **GJC2** — Gap junction gamma-2 protein [Candidate gene tested in]
  - Função: One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. May play a role
- **RAB3GAP2** — Rab3 GTPase-activating protein non-catalytic subunit [Candidate gene tested in]
  - Função: Regulatory subunit of the Rab3 GTPase-activating (Rab3GAP) complex composed of RAB3GAP1 and RAB3GAP2, which accelerates the otherwise slow GTP hydrolysis catalyzed by Rab proteins (PubMed:9733780, Pub
- **AP5Z1** — AP-5 complex subunit zeta-1 [Candidate gene tested in]
  - Função: As part of AP-5, a probable fifth adaptor protein complex it may be involved in endosomal transport. According to PubMed:20613862 it is a putative helicase required for efficient homologous recombinat
- **PGAP1** — GPI inositol-deacylase [Candidate gene tested in]
  - Função: GPI inositol-deacylase that catalyzes the remove of the acyl chain linked to the 2-OH position of inositol ring from the GPI-anchored protein (GPI-AP) in the endoplasmic reticulum (PubMed:24784135, Pu
- **AMPD2** — AMP deaminase 2 [Candidate gene tested in]
  - Função: AMP deaminase plays a critical role in energy metabolism. Catalyzes the deamination of AMP to IMP and plays an important role in the purine nucleotide cycle
- **FLRT1** — Leucine-rich repeat transmembrane protein FLRT1 [Candidate gene tested in]
  - Função: Plays a role in fibroblast growth factor-mediated signaling cascades that lead to the activation of MAP kinases. Promotes neurite outgrowth via FGFR1-mediated activation of downstream MAP kinases. Pro
- **TFG** — Protein TFG [Candidate gene tested in]
  - Função: Plays a role in the normal dynamic function of the endoplasmic reticulum (ER) and its associated microtubules (PubMed:23479643, PubMed:27813252). Required for secretory cargo traffic from the endoplas
- **IBA57** — Iron-sulfur cluster assembly factor IBA57, mitochondrial [Candidate gene tested in]
  - Função: Mitochondrial protein involved in the maturation of mitochondrial [4Fe-4S]-proteins in the late stage of the iron-sulfur cluster assembly pathway (PubMed:22323289, PubMed:23462291). Operates in cooper
- **HACE1** — E3 ubiquitin-protein ligase HACE1 [Candidate gene tested in]
  - Função: E3 ubiquitin-protein ligase involved in Golgi membrane fusion and regulation of small GTPases (PubMed:15254018, PubMed:21988917, PubMed:22036506, PubMed:37537642, PubMed:38332367). Acts as a regulator
- **SPAST** — Spastin [Candidate gene tested in]
  - Função: ATP-dependent microtubule severing protein that specifically recognizes and cuts microtubules that are polyglutamylated (PubMed:11809724, PubMed:15716377, PubMed:16219033, PubMed:17389232, PubMed:2053
- **KLC2** — Kinesin light chain 2 [Candidate gene tested in]
  - Função: Kinesin is a microtubule-associated force-producing protein that plays a role in organelle transport. The light chain functions in coupling of cargo to the heavy chain or in the modulation of its ATPa

## Medicamentos em desenvolvimento (1)

- MIGLUSTAT — Fase Phase 2 (Ceramide glucosyltransferase inhibitor)
- Fonte: https://platform.opentargets.org/disease/MONDO_0019064

## Ensaios clínicos ativos (23)

- **NCT06692712** [RECRUITING]: Phase 3 Efficacy Study With Concurrent Control of IT MELPIDA in SPG50.Concurrent Controls. — https://clinicaltrials.gov/study/NCT06692712
- **NCT06572046** [RECRUITING]: STOP-HSP.Net: a Registry for Hereditary Spastic Paraplegia as an Integration Tool for Future Therapeutic Strategies — https://clinicaltrials.gov/study/NCT06572046
- **NCT05354622** [RECRUITING]: Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq) — https://clinicaltrials.gov/study/NCT05354622
- **NCT04712812** [RECRUITING]: Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia — https://clinicaltrials.gov/study/NCT04712812
- **NCT06553976** [RECRUITING]: Spastic Paraplegia - Centers of Excellence Research Network — https://clinicaltrials.gov/study/NCT06553976
- **NCT07478172** [RECRUITING]: Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease — https://clinicaltrials.gov/study/NCT07478172
- **NCT07090057** [RECRUITING]: The Effect of Targeting the Plantaris Muscle-tendon in Surgical Correction of Ankle Equinus in Children — https://clinicaltrials.gov/study/NCT07090057
- **NCT01568658** [RECRUITING]: Genetic and Physical Study of Childhood Nerve and Muscle Disorders — https://clinicaltrials.gov/study/NCT01568658
- **NCT07417943** [RECRUITING]: Neuromodulation to Enhance Motor Function in HSP — https://clinicaltrials.gov/study/NCT07417943
- **NCT07136844** [RECRUITING]: Gait Analysis Parameter and Upper Limb Evaluation in Adult Patients With Neurological or Metabolic Pathology — https://clinicaltrials.gov/study/NCT07136844

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## Importante

O Raras **não diagnostica e não prescreve**. Esta página é educativa e informativa.
Pacientes devem consultar profissionais de saúde qualificados para decisões clínicas.

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