TBCK Syndrome

TBCK-related encephalopathy is a rare neurogenetic disorder. It is an autosomal recessive disease, meaning it is caused by genetic mutations usually carried by both parents. There are about 35 reported cases worldwide.

TBCK syndrome causes a wide range of symptoms. Most children with TBCK have developmental delays, ranging from moderate to severe, and low muscle tone. Some children also have seizures and weakness. The full list of potential symptoms includes:

• Coarse facial features
• Congenital hypotonia (low muscle tone)
• Global developmental delay, ranging from moderate to severe
• Dysphagia (difficulty swallowing)
• Respiratory insufficiency due to weakness
• Epilepsy
• MRI features, including white matter changes, cerebellar atrophy and thin corpus callosum
• Absent/severely delayed expressive language
• Hyporeflexia/areflexia (below normal or absent reflexes)
• Hypothyroidism (underactive thyroid gland)
• Osteopenia (weak bones)
• Hypercholesterolemia (high cholesterol)
• Frequent urinary tract infections/nephrolithiasis (kidney stones)

Diagnosis of TBCK syndrome is often done through whole exome sequencing, one of the most extensive genetic tests available, which compares the DNA of the parents and child. Targeted TBCK gene testing can also confirm the diagnosis in patients with known family history or high clinical suspicion of this disorder.

All patients with TBCK-related encephalopathy are evaluated for developmental delays and started on appropriate therapies. We also carefully evaluate children for feeding difficulties, seizures and respiratory insufficiency. Seizures are treated symptomatically, with many patients responding well initially to levetiracetam. Many patients present initially with provoked seizures (in setting of fever or illness) and then progress to symptomatic epilepsy.

Children’s Hospital of Philadelphia is actively engaged in natural history and phenotypic variability studies of TBCK. CHOP physicians Dr. Xilma Ortiz-Gonzalez and Dr. Elizabeth Bhoj are amongst the co-discoverers of the syndrome and have been collaborating with the common goal of advancing the understanding and ultimately treatment for this progressive disease. Contact us at tbckresearch@chop.edu if you have a patient that you would like to refer to our studies.