Godava Marek, Filipova Hana, Dubrava Lubomir, Vrtel Radek, Michalkova Kamila, Janikova Maria, Bakaj-Zbrozkova Lenka, Navratil Jiri
Centre of Fetal Medicine and Medical Genetics, FETMED, Olomouc, Czech Republic.
Laboratory of Medical Genetics, SPADIA LAB a.s., Novy Jicin, Czech Republic.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2017 Sep;161(3):326-329. doi: 10.5507/bp.2017.023. Epub 2017 Jun 12.
Presence of multiple cardiac rhabdomyomas is one of the major features of Tuberous sclerosis (TSC), but isolated progressing single giant rhabdomyoma is very rare and not typical of TSC.
This report presents family without obvious history of TSC with occurrence of giant mediastinal rhabdomyoma affecting the haemodynamics in male foetus, without other TSC symptoms. Girl from the next gravidity had prenatally detected multiple rhabdomyomas and small subcortical tuber of brain detected after birth. DNA analysis found novel c.4861A>T TSC2 variant and large deletion in TSC2 in tumour tissue from male foetus. The novel TSC2 variant was also present in the girl and her healthy father, in silico analysis suggested its functional effect on TSC2. Brain MRI of the father detected mild TSC specific abnormality.
We suggest the novel TSC2 mutation is a cause of mild TSC in this family and has reduced expression. The clinical and molecular findings in this family also emphasize that TSC diagnosis should be also evaluated in case of single giant foetal cardiac rhabdomyoma.
多发性心脏横纹肌瘤的存在是结节性硬化症（TSC）的主要特征之一，但孤立的进行性单个巨大横纹肌瘤非常罕见，并非TSC的典型表现。
本报告介绍了一个无明显TSC家族史的家庭，该家庭中一名男性胎儿出现巨大纵隔横纹肌瘤，影响血流动力学，且无其他TSC症状。下一胎的女孩在产前检测出多个横纹肌瘤，出生后检测出脑皮质下小结节。DNA分析在男性胎儿肿瘤组织中发现新的c.4861A>T TSC2变异以及TSC2大片段缺失。该新的TSC2变异也存在于女孩及其健康父亲体内，计算机模拟分析提示其对TSC2有功能影响。父亲的脑部MRI检测到轻度TSC特异性异常。
我们认为该新的TSC2突变是这个家族轻度TSC的病因，且表达降低。这个家族的临床和分子学发现也强调，在出现单个巨大胎儿心脏横纹肌瘤的情况下，也应评估TSC诊断。
