ESPE Abstracts

Keywords: Ulnar-mammary syndrome; TBX3 gene; Hypogonadotropic hypogonadism; Skeletal anomalies, Polydactyly

Background: Hypogonadotropic hypogonadism (HH) is an increasingly frequent medical condition deriving from a dysregulation of the hypothalamic-pituitary-gonadal axis function, which leads to low sex hormone levels associated with low gonadotropin levels. It can be congenital or acquired. Congenital HH, whose incidence is approximately 1-10:100,000 live births, is caused by genetic syndromes or is idiopathic; in both cases, it causes an impairment in the sexual development.

Case report: A 13-year-old male came to our attention with delayed puberty. Clinical examination showed overweight (BMI 0.91 SDS), abnormal conformation of the clavicle and complete absence of sexual development with bilateral testicular volume of 2 mL. Past medical history revealed bilateral feet polydactyly found at birth, while family history included an older sister with mammary hypoplasia and maternal history of breast cancer. Laboratory assessment revealed hypogonadotropic hypogonadism, while MRI imaging showed a normal pituitary gland. Bone age agreed with chronological age. The diagnosis of Ulnar-Mammary syndrome (UMS) was hypothesized based on familiar context and previous polydactyly and was confirmed with genetic analysis which revealed the variant c.1363_1370dup (Val458GlyfsTer177) of TBX3 gene. His mother was subsequently analysed and presented the same variant, although she didn’t seem to show the classical clinical features of UMS.

Conclusions: UMS is a rare autosomal dominant disorder with high phenotypic variability caused by heterozygous mutations in TBX3 gene. Typical clinical manifestations include skeletal anomalies such as ulnar defects and supernumerary or missing digits, mammary and apocrine gland hypoplasia and genital hypoplasia. These findings may be associated with endocrinological abnormalities, including short stature, obesity and delayed or absent sexual development. Paediatric endocrinologists should consider it in case of patients with delayed sexual development associated with post-axial skeletal defects and a family history suggestive for breast hypoplasia and/or cancer.