Autosomal recessive spastic paraplegia type 44

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ORPHA:320401OMIM:613206G11.4
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Overview

Autosomal recessive spastic paraplegia type 44 (SPG44) is an extremely rare inherited neurological condition that primarily affects the nervous system, causing progressive stiffness and weakness in the legs. It belongs to a large group of disorders known as hereditary spastic paraplegias (HSPs), which share the hallmark feature of gradually worsening leg spasticity due to degeneration of the longest nerve fibers in the spinal cord. SPG44 is caused by mutations in the GJC2 gene, which provides instructions for making a protein called connexin-47. This protein is important for the formation of gap junctions — tiny channels that allow communication between cells in the brain and spinal cord, particularly in the cells that produce myelin, the protective coating around nerve fibers. When this protein does not work properly, myelin formation and maintenance are disrupted, leading to the neurological symptoms seen in this condition. Patients with SPG44 typically develop difficulty walking due to progressive leg stiffness and weakness, often beginning in childhood or adolescence. Additional features may include problems with coordination, mild cognitive difficulties, and abnormalities visible on brain MRI that suggest impaired white matter (myelin). There is currently no cure for SPG44, and treatment focuses on managing symptoms through physical therapy, medications to reduce spasticity, and supportive care to maintain mobility and quality of life for as long as possible.

Also known as:

Key symptoms:

Progressive stiffness in the legs (spasticity)Difficulty walking that worsens over timeLeg weaknessIncreased muscle tone in the lower limbsExaggerated reflexes in the legsProblems with balance and coordinationMild intellectual disability or learning difficulties in some casesAbnormal gait patternWhite matter abnormalities on brain MRIPossible upper limb involvement in later stagesFatigue during physical activityFoot deformities such as high arches or curled toes

Clinical phenotype terms (16)— hover any for plain English
CNS hypomyelinationHP:0003429Abnormal auditory evoked potentialsHP:0006958Abnormality of somatosensory evoked potentialsHP:0007377Abnormal motor evoked potentialsHP:0012896Urinary bladder sphincter dysfunctionHP:0002839
Inheritance

Autosomal recessive

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

Age of Onset

Childhood

Begins in childhood, roughly ages 1 to 12

Orphanet ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for Autosomal recessive spastic paraplegia type 44.

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No actively recruiting trials found for Autosomal recessive spastic paraplegia type 44 at this time.

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No specialists are currently listed for Autosomal recessive spastic paraplegia type 44.

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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 Autosomal recessive spastic paraplegia type 44.

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Caregiver Resources

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Questions for your doctor

Bring these to your next appointment

  • Q1.How quickly is this condition likely to progress in my case or my child's case?,What physical therapy program do you recommend, and how often should sessions occur?,Are there medications that can help with the leg stiffness, and what are the side effects?,Should other family members be tested for carrier status?,Are there any clinical trials or research studies we could participate in?,What assistive devices or home modifications should we consider now or plan for in the future?,How should we monitor for any cognitive or learning difficulties?

Common questions about Autosomal recessive spastic paraplegia type 44

What is Autosomal recessive spastic paraplegia type 44?

Autosomal recessive spastic paraplegia type 44 (SPG44) is an extremely rare inherited neurological condition that primarily affects the nervous system, causing progressive stiffness and weakness in the legs. It belongs to a large group of disorders known as hereditary spastic paraplegias (HSPs), which share the hallmark feature of gradually worsening leg spasticity due to degeneration of the longest nerve fibers in the spinal cord. SPG44 is caused by mutations in the GJC2 gene, which provides instructions for making a protein called connexin-47. This protein is important for the formation of

How is Autosomal recessive spastic paraplegia type 44 inherited?

Autosomal recessive spastic paraplegia type 44 follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does Autosomal recessive spastic paraplegia type 44 typically begin?

Typical onset of Autosomal recessive spastic paraplegia type 44 is childhood. Age of onset can vary across affected individuals.