Spastic paraplegia-severe developmental delay-epilepsy syndrome

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ORPHA:464282OMIM:616756Q87.8
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Overview

Spastic paraplegia-severe developmental delay-epilepsy syndrome is an extremely rare genetic condition that affects the brain and nervous system. It is sometimes referred to by its Orphanet designation (ORPHA:464282). This syndrome combines three main features: spastic paraplegia (stiffness and weakness in the legs caused by damage to nerve pathways in the brain and spinal cord), severe developmental delay (children reach milestones like sitting, walking, and talking much later than expected, or may not reach them at all), and epilepsy (recurrent seizures). Children with this condition typically show signs very early in life, often in infancy, with poor muscle tone that may later evolve into spasticity, along with seizures that can be difficult to control with standard medications. Because this is such a rare condition, the treatment landscape is currently limited to managing symptoms rather than curing the underlying cause. Anti-epileptic medications are used to help control seizures, physical therapy and rehabilitation help manage spasticity and support motor development, and specialized educational support addresses the developmental delays. Affected children usually require multidisciplinary care involving neurologists, geneticists, rehabilitation specialists, and developmental pediatricians. Research into the genetic basis of this syndrome is ongoing, and understanding the specific gene involved (HACE1) has opened the door to potential future targeted therapies, though none are currently available.

Also known as:

Key symptoms:

Stiffness and tightness in the legs (spasticity)Severe delays in learning to sit, walk, and talkSeizures (epilepsy)Intellectual disabilityPoor muscle tone in early infancyDifficulty with coordination and balanceLimited or absent speechDifficulty feedingAbnormal movementsSmall head size (microcephaly)Difficulty with fine motor skills like grasping objectsBehavioral challengesReduced ability to walk independently

Clinical phenotype terms (40)— hover any for plain English
Inheritance

Autosomal recessive

Passed on when both parents carry the same gene change; often skips generations

Age of Onset

Infantile

Begins in infancy, roughly 1 month to 2 years old

Orphanet ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for Spastic paraplegia-severe developmental delay-epilepsy syndrome.

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No actively recruiting trials found for Spastic paraplegia-severe developmental delay-epilepsy syndrome at this time.

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No specialists are currently listed for Spastic paraplegia-severe developmental delay-epilepsy syndrome.

View NORD Rare Disease Centers ↗Undiagnosed Disease Network ↗

Treatment Centers

8 centers
🏥 NORD

Baylor College of Medicine Rare Disease Center

Baylor College of Medicine

📍 Houston, TX

🏥 NORD

Stanford Medicine Rare Disease Center

Stanford Medicine

📍 Stanford, CA

🔬 UDN

NIH Clinical Center Undiagnosed Diseases Program

National Institutes of Health

📍 Bethesda, MD

🔬 UDN

UCLA UDN Clinical Site

UCLA Health

📍 Los Angeles, CA

🔬 UDN

Baylor College of Medicine UDN Clinical Site

Baylor College of Medicine

📍 Houston, TX

🔬 UDN

Harvard/MGH UDN Clinical Site

Massachusetts General Hospital

📍 Boston, MA

🏥 NORD

Mayo Clinic Center for Individualized Medicine

Mayo Clinic

📍 Rochester, MN

👤 Mayo Clinic Center for Individualized Medicine

🏥 NORD

UCLA Rare Disease Day Program

UCLA Health

📍 Los Angeles, CA

Travel Grants

No travel grants are currently matched to Spastic paraplegia-severe developmental delay-epilepsy syndrome.

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Caregiver Resources

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Questions for your doctor

Bring these to your next appointment

  • Q1.What type of seizures does my child have, and what is the best medication to control them?,Are there any clinical trials or research studies that my child might be eligible for?,What therapies (physical, occupational, speech) should we start, and how often?,What should I do if my child has a prolonged seizure at home?,How will this condition affect my child's development over time, and what milestones can we work toward?,Should other family members be tested for carrier status of the HACE1 gene mutation?,What resources or support groups are available for families affected by this condition?

Common questions about Spastic paraplegia-severe developmental delay-epilepsy syndrome

What is Spastic paraplegia-severe developmental delay-epilepsy syndrome?

Spastic paraplegia-severe developmental delay-epilepsy syndrome is an extremely rare genetic condition that affects the brain and nervous system. It is sometimes referred to by its Orphanet designation (ORPHA:464282). This syndrome combines three main features: spastic paraplegia (stiffness and weakness in the legs caused by damage to nerve pathways in the brain and spinal cord), severe developmental delay (children reach milestones like sitting, walking, and talking much later than expected, or may not reach them at all), and epilepsy (recurrent seizures). Children with this condition typical

How is Spastic paraplegia-severe developmental delay-epilepsy syndrome inherited?

Spastic paraplegia-severe developmental delay-epilepsy syndrome follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does Spastic paraplegia-severe developmental delay-epilepsy syndrome typically begin?

Typical onset of Spastic paraplegia-severe developmental delay-epilepsy syndrome is infantile. Age of onset can vary across affected individuals.