TBCK-related encephalopathy-severe hypotonia-craniofacial dysmorphism syndrome

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ORPHA:488632OMIM:616900Q87.0
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Overview

TBCK-related encephalopathy with severe hypotonia and craniofacial dysmorphism (sometimes called TBCK syndrome or TBCK-related intellectual disability syndrome) is a rare genetic brain disorder caused by changes in the TBCK gene. This gene plays an important role in how brain cells grow, survive, and communicate with each other. When the TBCK gene does not work properly, the brain does not develop normally, leading to a range of serious neurological problems. Children with this condition typically show signs very early in life, including extremely low muscle tone (called hypotonia), severe intellectual disability, and delayed or absent developmental milestones such as sitting, standing, or speaking. Many children also have distinctive facial features, such as a small head size (microcephaly), widely spaced eyes, and other subtle differences in facial structure. Seizures are common and can be difficult to control. Brain imaging often shows that the brain is smaller than expected or has structural differences. There is currently no cure for TBCK syndrome. Treatment focuses on managing symptoms, supporting development, and improving quality of life. This includes anti-seizure medications, physical therapy, occupational therapy, speech therapy, and nutritional support. The condition is lifelong and typically causes profound disability, requiring full-time care throughout the person's life.

Key symptoms:

Severe low muscle tone (hypotonia) from birthProfound intellectual disabilityLittle or no speech developmentSeizures, often hard to controlVery small head size (microcephaly)Delayed or absent motor milestones (cannot sit, stand, or walk independently)Feeding difficulties, often requiring tube feedingDistinctive facial features such as widely spaced eyes and a flat nasal bridgeBrain shrinkage or structural brain abnormalities seen on MRIBreathing problems, especially in infancySpasticity (stiff muscles) in some childrenPoor or absent eye contact and visual tracking difficultiesGastroesophageal reflux and digestive problems

Clinical phenotype terms (50)— hover any for plain English
Progressive muscle weaknessHP:0003323Severe muscular hypotoniaHP:0006829Global brain atrophyHP:0002283Abnormal periventricular white matter morphologyHP:0002518Abnormal circulating lipid concentrationHP:0003119Multifocal seizuresHP:0031165
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 TBCK-related encephalopathy-severe hypotonia-craniofacial dysmorphism syndrome.

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No actively recruiting trials found for TBCK-related encephalopathy-severe hypotonia-craniofacial dysmorphism syndrome at this time.

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No specialists are currently listed for TBCK-related encephalopathy-severe hypotonia-craniofacial dysmorphism 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 TBCK-related encephalopathy-severe hypotonia-craniofacial dysmorphism syndrome.

Search all travel grants →NORD Financial Assistance ↗

Community

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Caregiver Resources

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Questions for your doctor

Bring these to your next appointment

  • Q1.What genetic testing do you recommend to confirm the diagnosis, and how long will results take?,What type of seizures does my child have, and what is the best medication plan to manage them?,Does my child need a feeding tube, and what are the signs that one is becoming necessary?,What therapies (physical, occupational, speech) should we start, and how often should they happen?,Is there any risk of the condition getting worse over time, and what signs should we watch for?,Are there any clinical trials or research studies we could consider joining?,What support services and community resources are available for our family?

Common questions about TBCK-related encephalopathy-severe hypotonia-craniofacial dysmorphism syndrome

What is TBCK-related encephalopathy-severe hypotonia-craniofacial dysmorphism syndrome?

TBCK-related encephalopathy with severe hypotonia and craniofacial dysmorphism (sometimes called TBCK syndrome or TBCK-related intellectual disability syndrome) is a rare genetic brain disorder caused by changes in the TBCK gene. This gene plays an important role in how brain cells grow, survive, and communicate with each other. When the TBCK gene does not work properly, the brain does not develop normally, leading to a range of serious neurological problems. Children with this condition typically show signs very early in life, including extremely low muscle tone (called hypotonia), severe in

How is TBCK-related encephalopathy-severe hypotonia-craniofacial dysmorphism syndrome inherited?

TBCK-related encephalopathy-severe hypotonia-craniofacial dysmorphism syndrome follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does TBCK-related encephalopathy-severe hypotonia-craniofacial dysmorphism syndrome typically begin?

Typical onset of TBCK-related encephalopathy-severe hypotonia-craniofacial dysmorphism syndrome is neonatal. Age of onset can vary across affected individuals.