Expanding the phenotype of children presenting with hypoventilation with biallelic TBCK pathogenic variants and literature review

Published:October 25, 2022DOI:


      • Hypoventilation has been reported in 46-83% of infants presenting with TBCK-related disorders.
      • Respiratory surveillance should be considered in the management of TBCK-related disorders.
      • TBCK-related disorders should be considered in infants with hypotonia, hypoventilation and white matter abnormalities on brain imaging.


      Individuals with biallelic TBCK pathogenic variants present in infancy with distinctive facial features, profound hypotonia, severe intellectual impairment and epilepsy. Although rare, it may mimic other neurogenetic disorders leading to extensive investigations. Improved understanding of the clinical phenotype can support early monitoring of complications due to respiratory insufficiency. We present six individuals who were found to have pathogenic biallelic TBCK variants. The clinico-radiological and diagnostic records were reviewed. Five individuals were diagnosed with hypoventilation, requiring respiratory support, highlighting the need for early respiratory surveillance. Characteristic brain imaging in our cohort included periventricular leukomalacia-like changes. We recommend screening for TBCK in hypotonic children with periventricular leukomalacia-like changes, particularly in the absence of prematurity.


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