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

## TL;DR

A rare genetic condition causing fetal hydrocephalus was diagnosed through prenatal imaging and confirmed by a new mutation in the L1CAM gene.

## Contribution

A novel L1CAM gene variant was identified in a case of X-linked hereditary hydrocephalus with prenatal imaging features.

## Key findings

- Prenatal MRI detected fetal hydrocephalus and an adducted thumb, suggesting XLH.
- A new frameshift variant in the L1CAM gene was confirmed through postnatal genetic testing.
- Non-invasive prenatal testing in a subsequent pregnancy identified a female fetus without hydrocephalus.

## 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.

X‐linked hereditary hydrocephalus (XLH) is a common cause of fetal hydrocephalus. L1CAM gene variants are causative, and novel pathogenic variants continue to emerge, making accurate diagnosis and variant evaluation increasingly important. This case highlights the importance of early genetic testing, as the identification of a novel L1CAM variant supported the prenatal diagnosis of X‐linked hydrocephalus and informed postnatal management.