TBCK syndrome: a rare multi-organ neurodegenerative disease

Emily L Durham; Rajesh Angireddy; Aaron Black; Ashley Melendez-Perez; Sarina Smith; Elizabeth M Gonzalez; Kristen G Navarro; Abdias Díaz; Elizabeth J K Bhoj; Kaitlin A Katsura

doi:10.1016/j.molmed.2023.06.009

TBCK syndrome: a rare multi-organ neurodegenerative disease

Trends Mol Med. 2023 Oct;29(10):783-785. doi: 10.1016/j.molmed.2023.06.009. Epub 2023 Jul 14.

Affiliations

¹ Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, PA, USA.
² Division of Human Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
³ Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, PA, USA; Division of Human Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
⁴ Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, PA, USA; Division of Human Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: [email protected].
⁵ Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, PA, USA; Department of Orofacial Sciences and Program in Craniofacial Biology, University of California, San Francisco, San Francisco, CA, USA. Electronic address: [email protected].

Abstract

TBCK syndrome is an autosomal recessive disorder primarily characterized by global developmental delay, hypotonia, abnormal magnetic resonance imaging (MRI), and distinctive craniofacial phenotypes. High variability is observed among affected individuals and their corresponding variants, making clinical diagnosis challenging. Here, we discuss recent breakthroughs in clinical considerations, TBCK function, and therapeutic development.

Keywords: bone abnormalities; developmental delay; hypotonia; neurodegeneration; neurological disorder; respiratory complications.

MeSH terms

Humans
Muscle Hypotonia / genetics
Muscle Hypotonia / pathology
Neurodegenerative Diseases* / diagnosis
Neurodegenerative Diseases* / etiology
Phenotype
Protein Serine-Threonine Kinases* / genetics

Substances

Protein Serine-Threonine Kinases
TBCK protein, human

Grants and funding

K08 NS109281/NS/NINDS NIH HHS/United States