Microcephalic primordial dwarfism due to ZNF335 deficiency

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ORPHA:329228OMIM:615095Q87.1
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Overview

Microcephalic primordial dwarfism due to ZNF335 deficiency is an extremely rare genetic condition that affects brain development and overall body growth from very early in life. The disease is caused by harmful changes (mutations) in the ZNF335 gene, which plays an important role in how the brain develops before birth. Children born with this condition have a very small head size (microcephaly) and are significantly smaller than expected for their age (primordial dwarfism), meaning the growth restriction begins before birth and continues after. The brain is often severely underdeveloped, with a simplified structure that lacks the normal folds and layers seen in a healthy brain. This leads to profound intellectual disability, seizures, and significant developmental delays. Other features may include distinctive facial features and problems with other organ systems. Because the condition is so rare, there are currently no specific treatments or cures. Care is supportive and focuses on managing symptoms such as seizures, feeding difficulties, and developmental needs. A team of specialists is typically needed to provide the best possible care. The prognosis is unfortunately very poor, with many affected children having a significantly shortened lifespan due to the severity of brain malformation and associated complications.

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Key symptoms:

Extremely small head size present at birthVery short stature and low birth weightSevere intellectual disabilitySeizuresSimplified brain structure with reduced foldsFeeding difficultiesFailure to thriveProfound developmental delaysAbnormal muscle toneDistinctive facial featuresVision problemsLimited or absent speechMovement difficulties

Clinical phenotype terms (9)— hover any for plain English
Abnormal cerebral morphologyHP:0002060Small cerebral cortexHP:0002472Abnormal cerebral cortex morphologyHP:0002538Simplified gyral patternHP:0009879Abnormal neuron morphologyHP:0012757
Inheritance

Autosomal recessive

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

Age of Onset

Neonatal

Begins at or shortly after birth (first 4 weeks)

Orphanet ↗OMIM ↗NORD ↗

Treatments

No FDA-approved treatments are currently listed for Microcephalic primordial dwarfism due to ZNF335 deficiency.

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No specialists are currently listed for Microcephalic primordial dwarfism due to ZNF335 deficiency.

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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

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Community

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Questions for your doctor

Bring these to your next appointment

  • Q1.What is the expected course of this condition for my child specifically?,What seizure medications are recommended, and what side effects should I watch for?,Does my child need a feeding tube, and how do I manage it at home?,What therapies (physical, occupational) would benefit my child?,Should we involve palliative care, and what does that look like?,What is the chance of having another child with this condition, and is prenatal testing available?,Are there any research studies or registries we should know about?

Common questions about Microcephalic primordial dwarfism due to ZNF335 deficiency

What is Microcephalic primordial dwarfism due to ZNF335 deficiency?

Microcephalic primordial dwarfism due to ZNF335 deficiency is an extremely rare genetic condition that affects brain development and overall body growth from very early in life. The disease is caused by harmful changes (mutations) in the ZNF335 gene, which plays an important role in how the brain develops before birth. Children born with this condition have a very small head size (microcephaly) and are significantly smaller than expected for their age (primordial dwarfism), meaning the growth restriction begins before birth and continues after. The brain is often severely underdeveloped, with

How is Microcephalic primordial dwarfism due to ZNF335 deficiency inherited?

Microcephalic primordial dwarfism due to ZNF335 deficiency follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does Microcephalic primordial dwarfism due to ZNF335 deficiency typically begin?

Typical onset of Microcephalic primordial dwarfism due to ZNF335 deficiency is neonatal. Age of onset can vary across affected individuals.