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spastic paraplegia-severe developmental delay-epilepsy syndrome - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

spastic paraplegia-severe developmental delay-epilepsy syndrome

MONDO:0014764

Also known as:SPPRS syndromespastic paraplegia-psychomotor retardation-seizures syndromeSPPRS

Overview

Spastic paraplegia-severe developmental delay-epilepsy syndrome is a rare, genetic, complex spastic paraplegia disorder characterized by an infantile-onset of psychomotor developmental delay with severe intellectual disability and poor speech acquisition, associated with seizures (mostly myoclonic), muscular hypotonia which may be noted at birth, and slowly progressive spasticity in the lower limbs leading to severe gait disturbances. Ocular abnormalities and incontinence are commonly associated. Other symptoms may include verbal dyspraxia, hypogenitalism, macrocephaly and sensorineural hearing loss, as well as dystonic movements and ataxia with upper limb involvement.

GeneticsAutosomal recessive · HACE1 (chr 6)

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 common findings: Seizure, Lower limb spasticity, Waddling gait, and Inner ear hearing loss (sensorineural hearing impairment); and sometimes findings: Inability to walk, Short stature, Dystonia, and Generalized myoclonic seizure and others. 28 total HPO annotations.

Organ System	Phenotype Count	Example Features
Brain and nerves	12	Inability to walk, Dystonia, Generalized myoclonic seizure

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.

HACE1 encodes HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (909 aa). E3 ubiquitin-protein ligase involved in Golgi membrane fusion and regulation of small GTPases. Highest expression in Brain Cerebellar Hemisphere (24.8 TPM) and Brain Cerebellum (23.5 TPM).

Spastic paraplegia-severe developmental delay-epilepsy syndrome is associated with mutations in the HACE1 gene on chromosome 6.

HACE1 is classified as a druggable target (Enzyme category) with score 0.0.

Diagnosis

Genetic testing for HACE1 is available. Testing is considered confirmatory for diagnosis.

Biomarker and diagnostic research for spastic paraplegia-severe developmental delay-epilepsy syndrome has been reported in the published literature.

Prognosis

Phenotype severity distribution: 4 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 spastic paraplegia-severe developmental delay-epilepsy syndrome.

119 publications have been identified in PubMed for spastic paraplegia-severe developmental delay-epilepsy syndrome. Research spans Review / Meta-Analysis (30%), Epidemiology / Natural History (22%), and Basic Science / Preclinical (18%).

Research Type	Count	% of Total
Research summaries	36	30%

Data assembled from 6 of 12 sources · Last updated Sep 19, 2026, 6:32 AM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

OMIM

Online Mendelian Inheritance in Man

OMIM:616756

Orphanet

European rare disease database

Orphanet:464282

GARD

Genetic and Rare Diseases Info Center

GARD:17816

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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Kisho

spastic paraplegia-severe developmental delay-epilepsy syndrome

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

spastic paraplegia-severe developmental delay-epilepsy syndrome

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