Biallelic ZBTB11 Variants: A Neurodevelopmental Condition with Progressive Complex Movement Disorders

Area of Science:

• Genetics
• Neurology
• Rare Diseases

Background:

• Biallelic ZBTB11 variants are linked to intellectual developmental disorder, MRT69.
• ZBTB11-related disorders (ZBTB11-RD) are ultrarare genetic conditions.

Purpose of the Study:

• To characterize the clinical and genetic spectrum of ZBTB11-RD.
• To emphasize the progressive complex movement abnormalities associated with ZBTB11-RD.

Main Methods:

• Clinical and genetic data from 13 new and 16 previously reported individuals with biallelic ZBTB11 variants were analyzed.
• Patient ages ranged from 2 to 50 years.

Main Results:

• Neurodevelopmental phenotypes varied in severity, with ocular and neurological features present in all patients.
• Complex movement abnormalities (ataxia, dystonia, myoclonus, stereotypies, tremor) were observed in 11 new patients.
• Cataracts were noted in 7 new patients, and deep brain stimulation showed success in one case of progressive dystonia. Thirteen novel variants were identified.

Conclusions:

• ZBTB11-RD presents with a spectrum of neurodevelopmental phenotypes.
• Progressive movement abnormalities are a key feature of ZBTB11-RD, occurring alongside neurodevelopmental issues.