TBX6-associated Congenital Scoliosis: A New Congenital Scoliosis Subtype Defined by Chinese

Abstract

Congenital scoliosis (CS) is a congenital spinal deformity that originates from abnormal spinal development in embryo. Characterized by rapid progression, severe deformity, and many complications, CS brings heavy economic and mental burden to patients and their families. At present, there is no good treatment for the etiology of spinal deformity. Due to the lack of early prediction methods, patients are often not detected until the appearance of malformation, and the treatment is mainly passive, conservative or traumatic treatment with braces or surgery to control the progression of the disease. Therefore, the exploration of early diagnosis methods and effective etiological intervention targets for spinal deformity is currently an international research hotspot. The orthopaedic team of Peking Union Medical College Hospital, focusing on the molecular genetics research and clinical application of CS, has built the world leading genetic research system of skeletal deformity. Through a multi-center large-scale cohort study, the team has found and demonstrated that compound inheritance of a rare null mutation and a hypomorphic allele of TBX6 led to CS. A set of genotype-phenotype integrated analysis method has been established, which successfully defined a new subtype of CS (TBX6-associated congenital scoliosis, TACS) and realized accurate clinical prediction of this unique subtype. With the establishment of the first genetics clinic of skeletal deformity in China, the clinical transformation of research results can thus be realized, providing a new paradigm for the etiology research and clinical application of skeletal deformity.

Keywords

• congenital scoliosis
• tbx6
• tbx6-associated congenital scoliosis
• molecular genetics
• clinical practice