Osman Khaled, Asaly Ayman, Halloun Rana, Paperna Tamar, Pollack Shirley, Magen Daniella, Tiosano Dov, Weiss Karin
Genetics Institute, Rambam Health Care Campus, Haifa, Israel.
Division of Pediatric Endocrinology, Ruth Rappaport Children's Hospital, Rambam Health Care Campus, Haifa, Israel.
Eur J Med Genet. 2025 Feb;73:104994. doi: 10.1016/j.ejmg.2025.104994. Epub 2025 Jan 7.
Ulnar mammary syndrome (UMS) is an autosomal dominant disorder caused by heterozygous pathogenic variants in the T-box transcription factor 3 (TBX3) gene. The phenotype is classically characterized by upper limb defects and apocrine/mammary gland hypoplasia. Endocrine abnormalities include hypogonadotropic hypogonadism (HH), partial growth hormone deficiency and dysmorphic features, while ectopic pituitary gland and various congenital anomalies have also been described. Here, we report a family with a unique clinical presentation.
Exome sequencing was performed for twin siblings with micropenis, neonatal hypogonadism, and congenital giant bladder diverticula.
We identified a novel likely pathogenic heterozygous TBX3 variant c.844G>T; p.(Gly282Cys) inherited from the apparently unaffected mother. Reverse phenotyping confirmed that the mother and the twins had features suggestive of UMS spectrum. The mother had been diagnosed as having HH, with an hypoplastic pituitary gland. The physical examination revealed a bifid nasal tip and a bi-lobulated tongue tip typical for UMS with no apparent limb or mammary defects.
This report extends the phenotype of the TBX3-related disorder to include HH and bladder anomalies without significant limb or mammary manifestations.
尺侧乳腺综合征（UMS）是一种常染色体显性疾病，由T盒转录因子3（TBX3）基因的杂合致病变异引起。其典型表型特征为上肢缺陷和顶泌汗腺/乳腺发育不全。内分泌异常包括低促性腺激素性性腺功能减退（HH）、部分生长激素缺乏和畸形特征，同时也有异位垂体和各种先天性异常的报道。在此，我们报告一个具有独特临床表现的家系。
对患有小阴茎、新生儿性腺功能减退和先天性巨大膀胱憩室的双胞胎兄弟姐妹进行外显子组测序。
我们鉴定出一个新的可能致病的杂合TBX3变异c.844G>T；p.（Gly282Cys），该变异从表面上未受影响的母亲遗传而来。反向表型分析证实母亲和双胞胎具有提示UMS谱系的特征。母亲被诊断为患有HH，垂体发育不全。体格检查发现典型的UMS表现为鼻尖分叉和舌尖分叶，无明显肢体或乳腺缺陷。
本报告将TBX3相关疾病的表型扩展到包括HH和膀胱异常，而无明显的肢体或乳腺表现。
