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hereditary spastic paraplegia 28 - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

hereditary spastic paraplegia 28

MONDO:0012256

Also known as:DDHD1 autosomal recessive pure spastic paraplegiaSPG28autosomal recessive pure spastic paraplegia caused by mutation in DDHD1

Overview

Autosomal recessive spastic paraplegia type 28 is a pure form of hereditary spastic paraplegia characterized by a childhood or adolescent onset of slowly progressive, pure crural muscle spastic paraparesis which manifests with mild lower limb weakness, gait difficulties, extensor plantar responses, and hyperreflexia of lower extremities. Less common manifestations reported include cerebellar oculomotor disturbance with saccadic eye pursuit, pes cavus and scoliosis. Some patients also present pin and vibration sensory loss in distal legs.

GeneticsAutosomal recessive · DDHD1 (chr 14)

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

Features include very common findings: Babinski sign and Overactive reflexes (hyperreflexia); and common findings: Peripheral axonal neuropathy, Sideways curvature of the spine (scoliosis), Pes cavus, and Lower limb spasticity and others. 17 total HPO annotations.

Organ System	Phenotype Count	Example Features
Brain and nerves	9	Peripheral axonal neuropathy, Difficulty walking (gait disturbance), Babinski sign

Genetic Landscape

Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.

DDHD1 encodes DDHD domain containing 1 (900 aa). Phospholipase A1 (PLA1) that hydrolyzes ester bonds at the sn-1 position of glycerophospholipids producing a free fatty acid and a lysophospholipid (Probable). Highest expression in Cells EBV-transformed lymphocytes (26.6 TPM) and Testis (20.0 TPM).

Hereditary spastic paraplegia 28 is associated with mutations in the DDHD1 gene on chromosome 14.

The DDHD1 protein participates in DDHD1,2 hydrolyse PA pathway.

DDHD1 is classified as a druggable target (Phospholipase category) with score 3.2.

Diagnosis

Genetic testing for DDHD1 is available. Testing is considered confirmatory for diagnosis.

Biomarker and diagnostic research for hereditary spastic paraplegia 28 has been reported in the published literature.

Prognosis

Phenotype severity distribution: 2 very common features, 13 common features.

Estimated prevalence: <1 in 1,000,000 (VERY_RARE).

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

No clinical trials have been registered for hereditary spastic paraplegia 28.

14 publications have been identified in PubMed for hereditary spastic paraplegia 28. Research spans Epidemiology / Natural History (36%), Review / Meta-Analysis (21%), and Case Report / Case Series (21%).

Research Type	Count	% of Total
Disease patterns and progression	5	36%

Data assembled from 6 of 12 sources · Last updated Sep 19, 2026, 5:33 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:609340

Orphanet

European rare disease database

Orphanet:101008

GARD

Genetic and Rare Diseases Info Center

GARD:16941

Questions for Your Care Team

→Should my partner and I meet with a genetic counselor to discuss carrier status and family planning?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

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hereditary spastic paraplegia 28

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Prognosis

Research Landscape

Medical References

External Resources

OMIM

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Explore clinical features

Recent Publications

hereditary spastic paraplegia 28

Overview

Clinical Presentation

Genetic Landscape

Diagnosis

Prognosis

Research Landscape

Medical References

External Resources

OMIM

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Explore clinical features

Recent Publications