Horiuchi Ryosuke, Sato Hiroshi, Asai Chinami, Hamaguchi Fumika, Takaishi Yu, Fujiwara Kensuke, Atsumi Yukari, Ando Yukiko, Kawata Takahito, Kakui Kazuyo
Department of Obstetrics and Gynecology Hyogo Prefectural Amagasaki General Medical Center Amagasaki Hyogo Japan.
Department of Clinical Genetics Hyogo Prefectural Amagasaki General Medical Center Amagasaki Hyogo Japan.
Clin Case Rep. 2025 Aug 14;13(8):e70792. doi: 10.1002/ccr3.70792. eCollection 2025 Aug.
X-linked hereditary hydrocephalus (XLH) is a congenital form of hydrocephalus caused by variants in the L1CAM gene on the X chromosome. Diagnosis is often made prenatally via ultrasound or magnetic resonance imaging (MRI), but specific features such as adducted thumbs are subtle and easily missed. We report a case in which prenatal MRI at 34 weeks gestation revealed fetal hydrocephalus and an adducted thumb, suggestive of XLH. Postnatal genetic testing confirmed a previously unreported frameshift variant in the L1CAM gene, c.2248dup (p.Tyr750LeufsTer36). The male infant required neurosurgical intervention and was also diagnosed with Hirschsprung's disease. Genetic testing confirmed that the mother was a heterozygous carrier. In a subsequent pregnancy, non-invasive prenatal testing (NIPT) predicted a female fetus with no hydrocephalus. This case highlights the importance of thorough imaging and genetic evaluation in suspected XLH, especially given the increasing discovery of novel pathogenic variants.
X连锁遗传性脑积水(XLH)是一种先天性脑积水,由X染色体上L1CAM基因的变异引起。诊断通常通过产前超声或磁共振成像(MRI)进行,但诸如拇指内收等特定特征较为细微,容易被忽视。我们报告了一例病例,妊娠34周时的产前MRI显示胎儿脑积水和拇指内收,提示XLH。产后基因检测证实L1CAM基因存在一个先前未报告的移码变异,即c.2248dup(p.Tyr750LeufsTer36)。该男婴需要神经外科干预,同时还被诊断患有先天性巨结肠症。基因检测证实母亲是杂合子携带者。在随后的一次妊娠中,无创产前检测(NIPT)预测胎儿为女性,无脑积水。该病例强调了在疑似XLH中进行全面影像学和基因评估的重要性,尤其是考虑到新的致病变异不断被发现。