X‐Linked Hereditary Hydrocephalus Diagnosed in the Fetal Period With Adducted Thumb and a Novel L1CAM Variant: A Case Report

ABSTRACT 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...

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Main Authors: Ryosuke Horiuchi, Hiroshi Sato, Chinami Asai, Fumika Hamaguchi, Yu Takaishi, Kensuke Fujiwara, Yukari Atsumi, Yukiko Ando, Takahito Kawata, Kazuyo Kakui
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Clinical Case Reports
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Online Access:https://doi.org/10.1002/ccr3.70792
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Summary:ABSTRACT 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.
ISSN:2050-0904