ESPE Abstracts

Ulnar-mammary syndrome (UMS) is caused by TBX3 mutation and is a disorder characterized by altered limb, breast, tooth, hair, apocrine gland, and genital development. The detailed genotype-phenotype correlation of TBX3 -related diseases was analysed by the 5.5th UMS case analysis, and all reported cases of UMS were summarized and discussed.

Methods: The clinical and genetic data of a boy with UMS were carefully analysed. Literature papers on UMS published up to February 2023 were retrieved. Clinical biochemical data, pituitary MRI data, and whole exome gene detection data were analysed. The impact of the mutation and stability of TBX3 on the mRNA structure was analysed by the M-fold program. Three-dimensional protein structures were calculated and analysed.

Results: The patient presented with a hypoplastic left fifth finger, an absence of interphalangeal creases, a large space between the fourth and fifth fingers, no bending ability of the fifth finger, absent nipples, a high palates, a flat nasal bridge, a micropenis, microtestes, short stature and reduced axillary sweating. Pituitary magnetic resonance imaging (MRI) revealed pituitary gland hypoplasia with a thin pituitary stalk and loss of a strong signal in the posterior pituitary. A novel variant (c.1142_1146) in the TBX3 gene was detected in the proband and further verified by DNA sequencing. M-fold results revealed that the variant altered the mRNA structure and stability of the TBX3 gene. Clinical, genetic, and biochemical studies confirmed that the congenital normal idiopathic hypogonadotropic hypogonadism was associated with pituitary hypoplasia. After half a year of treatment with HCG, the micropenis was significantly improved. After one year of treatment with recombinant human growth hormone, the body height was largely improved.

Conclusion: One novel variant of the TBX3 gene was confirmed in an UMS patient, which enriched the spectrum of TBX3 genotypes.