Skip to content
How It Works
Explore
Resources Ask a Question
Who It's For
Patients
Decode results, prep for appointments, weigh options.
Caregivers & advocates
Carry the research load for someone you love.
Providers & clinicians
Resources for patients in your practice.
Log In Ask a Question
PubMed This is a summary of 8 peer-reviewed journal articles Updated
Medical Genetics · Autosomal Dominant Hereditary Spastic Paraplegia

Confirming Your Diagnosis

At a Glance

Autosomal Dominant Hereditary Spastic Paraplegia (AD-HSP) is diagnosed through genetic testing for mutations in genes like SPAST. Because each child has a 50% chance of inheriting it, genetic counseling is recommended to interpret test results and discuss family planning options.

Confirming a diagnosis of Autosomal Dominant Hereditary Spastic Paraplegia (AD-HSP) often relies on modern genetic technology to find the exact “molecular fingerprint” causing the condition [1][2].

Understanding Autosomal Dominant Inheritance

Autosomal Dominant means the condition is passed down through families. You only need one copy of the changed gene to develop the condition. Each child of an affected parent has a 50% chance of inheriting the gene mutation [3]. Even within the same family, symptom severity can vary widely [3][4].

The “Big Three” Genes

Three genes cause the vast majority of “pure” AD-HSP:

  1. SPAST (SPG4): The most common form worldwide [5][6]. Usually appears in adulthood.
  2. ATL1 (SPG3A): The most common cause of early-onset (childhood) HSP [7].
  3. REEP1 (SPG31): Often involves very slow progression [8].

Genetic Testing & The “Unsolved” Reality

Doctors use Next-Generation Sequencing (NGS) to scan many genes at once [1]. However, a “negative” test does not mean you don’t have HSP. Currently, over 50% of clinically diagnosed cases remain genetically unsolved [3].

Genetic Report Checklist

Ensure your report includes:

  • Variant Classification: Is it “Pathogenic” or “Likely Pathogenic”?
  • Gene Name and Subtype: (e.g., SPAST, SPG4).
  • Deletion/Duplication Analysis: Checked for missing/extra DNA chunks [1].
  • VUS status: A “Variant of Uncertain Significance” means the lab found a change but isn’t sure it causes disease. If you have a VUS, ask your doctor if testing other family members could help clarify the result, or if you should check back in 1-2 years as genetic databases update [3].

Family Planning and Genetic Counseling

Because of the 50% inheritance risk, family planning is a major consideration.

  • Genetic Counseling: Meeting with a genetic counselor can help you understand the risks and communication strategies for your family.
  • Testing Children: Guidelines generally advise against testing asymptomatic minors for adult-onset conditions, but discussing this with a counselor is vital.
  • Family Planning Options: If you are planning to have children, options like In Vitro Fertilization (IVF) with Preimplantation Genetic Testing (PGT) can ensure the mutation is not passed to the next generation [3].

Return to Home.

Common questions in this guide

How is Autosomal Dominant Hereditary Spastic Paraplegia inherited?
AD-HSP is passed down through families. You only need to inherit one copy of the mutated gene from an affected parent to develop the condition. This means each child of an affected parent has a 50 percent chance of inheriting the gene mutation.
What are the most common genes that cause AD-HSP?
The vast majority of pure AD-HSP cases are caused by mutations in three main genes. SPAST is the most common form worldwide and usually appears in adulthood. ATL1 is the most common cause of childhood HSP, and REEP1 often involves very slow symptom progression.
What does a Variant of Uncertain Significance (VUS) mean on my genetic report?
A VUS means the lab found a change in your DNA but does not have enough evidence to know if it actually causes AD-HSP. Your doctor may recommend testing other family members to clarify the result or checking back in a year or two as genetic databases are updated.
If my genetic test for HSP is negative, does that mean I don't have it?
Not necessarily. Even with modern next-generation sequencing, over half of people who are clinically diagnosed with HSP do not have an identified genetic mutation. A negative test does not completely rule out the disease.
Can I prevent passing AD-HSP to my children?
Yes, family planning options are available. By working with a genetic counselor, you can explore options like In Vitro Fertilization (IVF) combined with Preimplantation Genetic Testing (PGT) to ensure the genetic mutation is not passed to your children.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Does my genetic report identify a 'Pathogenic' variant, or is it a 'Variant of Uncertain Significance' (VUS)?
  2. 2.Given my specific mutation, what should I tell my siblings or children about their risk?
  3. 3.Can you refer me to a genetic counselor to discuss family planning options like IVF with PGT?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (8)
  1. 1

    Clinical and Genetic Spectrum in a Large Cohort of Hereditary Spastic Paraplegia.

    Cao Y, Zheng H, Zhu Z, et al.

    Movement disorders : official journal of the Movement Disorder Society 2024; (39(4)):651-662 doi:10.1002/mds.29728.

    PMID: 38291924
  2. 2

    Clinical and genetic spectra of 1550 index patients with hereditary spastic paraplegia.

    Méreaux JL, Banneau G, Papin M, et al.

    Brain : a journal of neurology 2022; (145(3)):1029-1037 doi:10.1093/brain/awab386.

    PMID: 34983064
  3. 3

    Hereditary Spastic Paraplegia in Alberta: Lessons from a Well-Defined Cohort Including the Indigenous Population.

    Assaedi E, Ashtiani S, Estiar MA, et al.

    Movement disorders clinical practice 2025; (12(9)):1346-1356 doi:10.1002/mdc3.70115.

    PMID: 40322871
  4. 4

    Phenotypic variability in a large kindred with spastic paraplegia associated with a novel REEP1 variant.

    Hjartarson HT, Skott H, Granberg T, Paucar M

    eNeurologicalSci 2024; (35()):100497 doi:10.1016/j.ensci.2024.100497.

    PMID: 38525447
  5. 5

    Comprehensive Characterization of Spastic Paraplegia in Korean Patients: A Single-Center Experience over Two Decades.

    Choi Y, Kim SH, Ahn SJ, et al.

    Yonsei medical journal 2026; (67(1)):34-41 doi:10.3349/ymj.2024.0500.

    PMID: 41431411
  6. 6

    Genetic mutation analysis of hereditary spastic paraplegia: A retrospective study.

    Cui F, Sun L, Qiao J, et al.

    Medicine 2020; (99(23)):e20193 doi:10.1097/MD.0000000000020193.

    PMID: 32501971
  7. 7

    A series of Greek children with pure hereditary spastic paraplegia: clinical features and genetic findings.

    Polymeris AA, Tessa A, Anagnostopoulou K, et al.

    Journal of neurology 2016; (263(8)):1604-11 doi:10.1007/s00415-016-8179-z.

    PMID: 27260292
  8. 8

    Transverse endoplasmic reticulum expansion in hereditary spastic paraplegia corticospinal axons.

    Zhu PP, Hung HF, Batchenkova N, et al.

    Human molecular genetics 2022; (31(16)):2779-2795 doi:10.1093/hmg/ddac072.

    PMID: 35348668

This page explains genetic testing for AD-HSP for educational purposes only. Always consult a genetic counselor or neurologist to interpret your specific test results and discuss family planning.

Get notified when new evidence is published on Autosomal dominant pure spastic paraplegia.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.