Ulnar-Mammary Syndrome

Ulnar-mammary syndrome (UMS) is a rare developmental disorder characterized by ulnar defects, mammary and apocrine gland hypoplasia and genital anomalies. Delayed puberty dental anomalies, short stature and obesity have also been described.

Epidemiology

The prevalence is unknown. Approximately 117 cases have been reported in the literature to date.

Clinical description

Upper limb defects are the most common presenting feature of UMS at birth. The limb phenotype ranges from normal limbs, hypoplasia of the distal phalanges of the little fingers or camptodactyly, to absent digits, absent or hypoplastic ulna and a reduced humerus. Abnormalites may be bilateral, but are frequently asymmetric and lower limb defects have not been reported. The variable mammary and apocrine features of UMS may not be apparent until puberty and include mammary gland tissue hypoplasia (leading to absence of breast development and the inability to lactate), areolar or nipple hypoplasia, inverted nipples and apocrine gland hypoplasia (that can result in diminished perspiration and body odor). Associated absence of axillary hair has also been described. Shared facial features of UMS include a wide face tapering to a prominent chin, a broad nasal tip, and a wide nasal base. Genital defects can include micropenis, shawl scrotum, cryptorchidism and imperforate hymen. Delayed puberty, particularly in males, is noted. Short stature is also common in individuals with UMS and a pituitary endocrine deficiency has been suggested as a possible cause. Abnormalities of the teeth with ectopic, hypoplastic or absent canines have been noted in a number of individuals with UMS. Cardiac defects (ventricular septal defects or conduction abnormalities) have been reported in a few cases.

Etiology

UMS is caused by mutations in the TBX3 gene (12q24.21). TBX3 is a member of the T-box gene family. These genes encode transcription factors that have been shown to be important in embryologic development and in the morphogenesis of multiple organ systems.

Genetic counseling

UMS is an autosomal dominant condition commonly reported in families with inter- and intra-familial variability in expression. Genetic counseling is possible.