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hereditary spastic paraplegia 54 - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

hereditary spastic paraplegia 54

MONDO:0014018

Also known as:DDHD2 autosomal recessive complex spastic paraplegiaSPG54autosomal recessive complex spastic paraplegia caused by mutation in DDHD2

Overview

A rare, complex form of hereditary spastic paraplegia characterized by the onset in early childhood of progressive spastic paraplegia associated with cerebellar signs, short stature, delayed psychomotor development, intellectual disability and, less commonly, foot contractures, dysarthria, dysphagia, strabismus and optic hypoplasia. SPG54 is caused by mutations in the DDHD2 gene (8p11.23) encoding phospholipase DDHD2.

GeneticsAutosomal recessive · DDHD2 (chr 8)

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 always present findings: Periventricular white matter hyperintensities, Overactive reflexes (hyperreflexia), Hypoplasia of the corpus callosum, and Global developmental delay and others; and common findings: Strabismus, Syringomyelia, Urinary incontinence, and Constipation and others. 25 total HPO annotations.

Organ System	Phenotype Count	Example Features
Brain and nerves	10	Muscle stiffness (rigidity), Periventricular white matter hyperintensities, Intellectual disability

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.

DDHD2 encodes DDHD domain containing 2 (711 aa). Diacylglycerol (DAG) and triacylglycerol (TAG) lipase required for proper lipid homeostasis in the central nervous system. Highest expression in Brain Cerebellar Hemisphere (52.8 TPM) and Brain Spinal cord cervical c-1 (43.3 TPM).

Hereditary spastic paraplegia 54 is associated with mutations in the DDHD2 gene on chromosome 8.

The DDHD2 protein participates in DDHD1,2 hydrolyse PA pathway.

DDHD2 is classified as a druggable target (Enzyme and Phospholipase categories) with score 0.0.

Diagnosis

Genetic testing for DDHD2 is available. Testing is considered confirmatory for diagnosis.

Biomarker and diagnostic research for hereditary spastic paraplegia 54 has been reported in the published literature.

Prognosis

Phenotype severity distribution: 5 always present features, 9 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 54.

17 publications have been identified in PubMed for hereditary spastic paraplegia 54. Research spans Epidemiology / Natural History (29%), Diagnostic / Biomarker (18%), and Case Report / Case Series (18%).

Research Type	Count	% of Total
Disease patterns and progression	5	29%

Data assembled from 6 of 12 sources · Last updated Sep 18, 2026, 7:16 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:615033

Orphanet

European rare disease database

Orphanet:320380

GARD

Genetic and Rare Diseases Info Center

GARD:17475

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 54

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 54

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