Prenatal Diagnosis of Recurrent Fetal Intracranial Hemorrhage and a Maternally Inherited COL4A1 Variant of Uncertain Significance: A Case Report With Maternal Reverse Phenotyping
6 affiliations
- 1Clinical Laboratory Honghe Hani and Yi Autonomous Prefecture Maternal and Child Health Hospital Honghe Yunnan Province People's Republic of China.
- 2Radiology Department Honghe Hani and Yi Autonomous Prefecture Maternal and Child Health Hospital Honghe Yunnan Province People's Republic of China.
- 3Prenatal Diagnosis Department Honghe Hani and Yi Autonomous Prefecture Maternal and Child Health Hospital Honghe Yunnan Province People's Republic of China.
- 4Ultrasound Department Honghe Hani and Yi Autonomous Prefecture Maternal and Child Health Hospital Honghe Yunnan Province People's Republic of China.
- 5Department of Medical Genetics Yunnan Maternal and Child Health Hospital Kunming Yunnan Province People's Republic of China.
- 6Department of Obstetrics Honghe Hani and Yi Autonomous Prefecture Maternal and Child Health Hospital Honghe Yunnan Province People's Republic of China.
Abstract
A 33‐year‐old woman with two consecutive pregnancies affected by fetal left periventricular germinal matrix hemorrhage (Grade IV) and progressive ventriculomegaly underwent trio whole‐exome sequencing. A heterozygous COL4A1 c.4249G>C (p.Gly1417Arg) variant, classified as a variant of uncertain significance, was identified in the fetus of the current pregnancy and found to be maternally inherited; concurrent copy‐number analysis incidentally detected a maternal 17p12 microdeletion encompassing PMP22, which was not inherited by the fetus. Systematic reverse phenotyping of the mother revealed right corticospinal tract Wallerian degeneration, persistent microscopic hematuria, a renal cyst, and retinal arteriolar changes—a phenotype compatible with the COL4A1‐associated spectrum, although molecular causality remains unproven. Following multidisciplinary review, the pregnancy was terminated at 29 weeks, primarily on the basis of the grave fetal prognosis, with early‐onset preeclampsia contributing to the overall maternal risk assessment; the mother's post‐termination course was uneventful, with resolution of hypertension and proteinuria. This case illustrates that recurrent anatomically congruent fetal intracranial hemorrhages may prompt maternal reverse phenotyping that identifies maternally inherited COL4A1 variants of uncertain significance, and underscores the need to distinguish phenotypic concordance from proven molecular causality in prenatal counseling.
Related
- Intracranial Hemorrhage in Patients Receiving Factor Xa Inhibitors: Challenges and Perspectives
- A Hemorrhagic Spinal Tumor Presenting as an Intracranial Subarachnoid Hemorrhage
- Drug-Drug Interaction Signals Between Anti-Amyloid-β Antibodies and Antithrombotic Drugs for Amyloid-Related Imaging Abnormalities and Intracranial Hemorrhage: A FAERS Disproportionality Analysis
- Clinical Characteristics and In-Hospital Course of Symptomatic Intracranial Hemorrhage After Intravenous Alteplase in Older Adults with Acute Ischemic Stroke: A Retrospective Cohort Study
- Is the International Normalized Ratio (INR) Enough? Reevaluating INR-Based Decision-Making for Four-Factor Prothrombin Complex Concentrate in Geriatric Warfarin-Associated Intracranial Hemorrhage: A Multicenter Cohort Study
BibTeX
@article{shi2026prenatal,
title = {{Prenatal Diagnosis of Recurrent Fetal Intracranial Hemorrhage and a Maternally Inherited COL4A1 Variant of Uncertain Significance: A Case Report With Maternal Reverse Phenotyping}},
author = {Wei Shi and Hongjing Xu and Caihong Pu and Yuanzhong Liang and Ting Zhao and Xueli Wang and Zhenxing Liu and Chunhua Zhang and Ting Li and Fengquan He},
journal = {Clinical Case Reports},
year = {2026},
month = oct,
doi = {10.1002/ccr3.73525},
url = {https://doi.org/10.1002/ccr3.73525},
note = {CC BY},
}
RIS
TY - JOUR
TI - Prenatal Diagnosis of Recurrent Fetal Intracranial Hemorrhage and a Maternally Inherited COL4A1 Variant of Uncertain Significance: A Case Report With Maternal Reverse Phenotyping
AU - Wei Shi
AU - Hongjing Xu
AU - Caihong Pu
AU - Yuanzhong Liang
AU - Ting Zhao
AU - Xueli Wang
AU - Zhenxing Liu
AU - Chunhua Zhang
AU - Ting Li
AU - Fengquan He
PY - 2026
DA - 2026/10/23
JO - Clinical Case Reports
DO - 10.1002/ccr3.73525
UR - https://doi.org/10.1002/ccr3.73525
AB - A 33‐year‐old woman with two consecutive pregnancies affected by fetal left periventricular germinal matrix hemorrhage (Grade IV) and progressive ventriculomegaly underwent trio whole‐exome sequencing. A heterozygous COL4A1 c.4249G>C (p.Gly1417Arg) variant, classified as a variant of uncertain significance, was identified in the fetus of the current pregnancy and found to be maternally inherited; concurrent copy‐number analysis incidentally detected a maternal 17p12 microdeletion encompassing PMP22, which was not inherited by the fetus. Systematic reverse phenotyping of the mother revealed right corticospinal tract Wallerian degeneration, persistent microscopic hematuria, a renal cyst, and retinal arteriolar changes—a phenotype compatible with the COL4A1‐associated spectrum, although molecular causality remains unproven. Following multidisciplinary review, the pregnancy was terminated at 29 weeks, primarily on the basis of the grave fetal prognosis, with early‐onset preeclampsia contributing to the overall maternal risk assessment; the mother's post‐termination course was uneventful, with resolution of hypertension and proteinuria. This case illustrates that recurrent anatomically congruent fetal intracranial hemorrhages may prompt maternal reverse phenotyping that identifies maternally inherited COL4A1 variants of uncertain significance, and underscores the need to distinguish phenotypic concordance from proven molecular causality in prenatal counseling.
SN - 2050-0904
ER -