TBX3- Related Disorder

Heterozygous pathogenic variants in TBX3 cause Ulnar-Mammary syndrome (UMS). The phenotype is classically characterized by upper limb defects, apocrine/mammary gland hypoplasia, hypogonadism, and various midline defects. However, the clinical spectrum is highly variable, and some individuals may present with a mild or atypical presentation without limb or mammary involvement. More recent studies identified a high rate of pituitary hypoplasia with decreased levels of gonadotropins and growth hormone in both males and females, in some cases as an isolated finding. We describe the main clinical features and molecular basis of the TBX3-related disorder and propose recommendations for the treatment and management of patients.