Symptoms
Though CTNNB1 Syndrome can vary in presentation and severity of symptoms, it is generally characterized by:
Mild-to-profound cognitive impairment
Microcephaly
Behavioral challenges
Sleep disturbances
Epilepsy
Truncal hypotonia
Peripheral spasticity
Dystonia
Exudative vitreoretinopathy
Strabismus
Refractive errors
Some additional reported symptoms include:
Intrauterine growth restriction
Feeding difficulties
Gastrointestinal problems
Tethered spinal cord
Congenital heart defects
Osteopenia
Scoliosis
Diagnosis
CTNNB1 Syndrome diagnosis is made through genetic testing using a Whole Exome or Whole Genome test. If you are looking for genetic testing, apply to Probably Genetic’s free, HIPAA-compliant whole exome sequencing program here.
Treatments
Current treatment focuses on managing symptoms, and varies based on patient symptoms and co-existing disorders. Because patients with CTNNB1 Syndrome have a wide range of symptoms and functional challenges, they are often followed by a multi-disciplinary team.
Treatments to address the disease itself are in development.
The Science Explained
CTNNB1 is the name of a gene that is located on the short arm (p) of chromosome 3 at position 22.1 (Cytogenetic Location: 3p22.1). Learn more about genetics and testing.
The CTNNB1 gene provides instructions for making a protein called beta-catenin. This protein is present in many types of cells and tissues, where it is primarily found at junctions that connect neighboring cells (adherens junctions). Beta-catenin plays an important role in sticking cells together (cell adhesion) and in communication between cells.
The beta-catenin protein is also involved in cell signaling as an essential part of the Wnt signaling pathway. Certain proteins in this pathway attach (bind) to beta-catenin, which triggers a multistep process that allows the protein to move into the cell nucleus. Once in the nucleus, beta-catenin interacts with other proteins to control the activity (expression) of particular genes. The Wnt signaling pathway promotes the growth and division (proliferation) of cells and helps determine the specialized functions a cell will have (differentiation). Wnt signaling is known to be involved in many aspects of development before birth. In adult tissues, this pathway plays a role in the maintenance and renewal of stem cells, which are cells that help repair tissue damage and can give rise to other types of cells.
Among its many activities, beta-catenin appears to play an important role in the normal function of hair follicles, which are specialized structures in the skin where hair growth occurs. This protein is active in cells that make up a part of the hair follicle known as the matrix. These cells divide and mature to form the different components of the hair follicle and the hair shaft. As matrix cells divide, the hair shaft is pushed upward and extends beyond the skin.
β-catenin is a sub-unit of a multiprotein complex, which is part of the Wnt signaling pathway.
β-catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcription. In humans, the CTNNB1 protein is encoded by the CTNNB1 gene. β- catenin is a subunit of the cadherin protein complex and acts as an intracellular signal transducer in the Wnt signaling pathway.
It is a member of the catenin protein family and homologous to γ-catenin, also known as plakoglobin. Beta-catenin is widely expressed in many tissues. In cardiac muscle, beta-catenin localizes to adherens junctions in intercalated disc structures, which are critical for electrical and mechanical coupling between adjacent cardiomyocytes.
Regulation of the Wnt signaling pathway is a finely tuned balancing act aimed toward cellular differentiation and the maintenance of tissue homeostasis.